{Page 6 HIV News} New Vac Fails

2020 ~March

"New HIV Vaccine Fails but Not All is Lost They Tell us"

Infectious disease specialist Glenda Gray spent the last 10 years of her life organizing a clinical trial on HVTN 702, a vaccine she and her team hoped could protect people from becoming infected with HIV.
But during a call with an independent board that evaluates trial safety and efficacy in January, their hopes were dashed; the vaccine was not working.
For many in the HIV community, the news came as a huge disappointment. HVTN 702 was one of the most promising treatments in the industry. Now, scientists are back to the drawing board, focusing on other HIV vaccine trials and research for success.
"One hopes there's going to be progress when one does an efficacy trial like this," says Mark Feinberg, CEO and president of the International AIDS Vaccine Initiative, who was not involved with the study. "But a lot of people were probably not too surprised, just because the challenge [to create an HIV vaccine] is so difficult."
There are currently 37.9 million people worldwide living with HIV/AIDS, and about 1.7 million new people became infected with HIV in 2018, according to UNAIDS. 
Scientists first saw a glimmer of hope in HVTN 702 more than a decade ago. In a groundbreaking 2009 study on an earlier version of the vaccine, researchers showed — for the first time — that a vaccine could prevent HIV infection. But the results of the trial conducted in Thailand were modest; the vaccine was only effective at preventing HIV in 31% of more than 16,000 trial participants. By contrast, most routine childhood vaccinations are at least 85% effective, according the World Health Organization.
Led by Gray, president of the South African Medical Research Council, researchers worked to improve the vaccine's effectiveness and try again, this time in South Africa — a country with one of the highest rates of HIV.
The team enrolled 5,407 sexually active men and women between the ages of 18 and 35. None had HIV but all lived in communities where HIV is prevalent. The volunteers were then randomly assigned to receive either the vaccine regimen — a series of six injections — or a placebo.
"We told all of them, 'You must behave like you are in the placebo arm,'" Gray explains, or as if they were not receiving a vaccine."We gave them condoms, contraception, HIV prevention counseling" and PrEP, medication that can help prevent HIV if taken daily.
Despite their efforts, 129 participants who had received the vaccine became infected with HIV after two years, while 123 infections occurred among participants receiving the placebo.
Scientists concluded that the vaccine did not prevent HIV, nor did it increase the chances of obtaining the disease.
The four-year trial was expected to end later this year, but after learning the results in January, Gray implemented a plan to quickly stop the study — which has cost upward of $100 million, according to Science. Participants were informed that the vaccine did not work, and all those who contracted HIV, an incurable disease, are now being put on treatment.
"We had to correspond with all of our participants ... the stakeholders, the study staff, the study investigators," Gray says. "Everyone is upset and sad."
HIV is a complex virus that targets and weakens the human immune system, which is normally responsible for fighting off diseases and infections. It also mutates rapidly, making mistakes as it replicates in the body.
"[This results] in viruses that are not all identical to each other," says Feinberg. "That means in every HIV infected person, there's tremendous genetic diversity." Antibodies created by the immune system to fight off the virus ultimately can't keep up with the mutations and fail to fight off HIV.
A vaccine for HIV faces the same challenge: it must trigger the creation of antibodies that can fight off all the different variations and subtypes of HIV. It also must have a long-lasting effect.
Vaccines trying to meet these standards are in the works across the globe.
The HIV Vaccine Trials Network, an international collaboration focused on the creation of an HIV vaccine, currently has two other ongoing vaccine trials: HVTN 705 and HVTN 706. HVTN 705 is being tested in Malawi, Mozambique, South Africa, Zambia and Zimbabwe, while HVTN 706 is undergoing tests in Europe and the Americas. The formulas behind the two vaccines vary slightly, but both are designed to induce immune reactions against a variety of HIV strains.
But Feinberg has his eye on the AMP (antibody mediated prevention) Studies, which are also organized by the HIV Vaccine Trials Network. The first results are due later this year.
While traditional vaccine trials give people a vaccine and wait for the human body to naturally produce antibodies against a disease or infection, AMP is giving antibodies directly to participants with IV infusions.
Participants in 11 countries are specifically receiving broadly neutralizing antibodies (BNAs), rare antibodies that form in about 20% of people who are infected with HIVand can block the infection of new cells—no matter the strain of HIV. 
"By infusing people with these antibodies, they are hoping they will protect them from acquiring HIV," Feinberg says. But unlike vaccines, which can offer protection for a number of years, the antibodies would need to be readministered periodically; they would not be a long-term solution.
If successful, however, these studies will show that the broadly neutralizing antibodies can guard against HIV infection — and will also spur scientists toward creating a vaccine that helps the human body naturally generate these antibodies. Feinberg's own organization is working on one such vaccine now.
Despite the most recent failure, giving up on a HIV vaccine is not an option for both Feinberg and Gray.
"The epidemic is out of control; we need a vaccine," says Gray. "Just because you fail, you don't stop trying. You dust yourself off and get up."
For Gray, that means working to understand why HVTN 702 failed.
But she finds cause for hope in HVTN 702's nickname Uhambo – which stands for 'journey' in the Zulu and Xhosa languages.
"We named it Uhambo," she says, "because we are on a journey to find an HIV vaccine."
Nadia Whitehead is a freelance journalist and science writer. Her work has appeared in Science, The Washington Post and NPR. Find her on Twitter@NadiaMacias

2019  Jan-Dec} Trending

Last posting for 2019 unless something comes up...don't hold your breath unless you can hold it  for 2 or 3 years:

(Click or copy and paste)


                      Illustration of two toolboxes

Factual case: A senior male became HIV at just pre-midlife. Started on Crixivan which was the first antiretroviral that started keeping people alive if not with awful side effects. Some people prefer to have died than to have had a came back or any of the other problems associated with this pill. But the research continued and meds we made specific to the immune system of the person and the type of virus they had. He took all the meds as they came out. As the test was made to show the efficacy of the meds he kept burning most of them. Six months a year ..but eventually he did become undetectable which means the virus could not be detected (under 50)> He has stayed undetectable for 8 yrs  except for the last news he got from his doctor was "if you burn these meds you will be shit out of luck because there is nothing else"(they have a straight honest relationship the Doctor and the patient). So imagine he has no more meds but he is doing well on what he is taking  (it's happened before, when he was doing well and then the meds failed) but with the knowledge that he is undetectable and can not give to anyone else which was always his fear particularly at one time he had a partner for five years and his partner was negative. When the relationship his partner went the same way he came into the relationship, the same health if not better. The way this HIV man looks at it if he lasts 5-10 years everything would have worked out. He is single now and hoping to find his last relationship and happy THAT HIV AT LAST FOR HM IS NOT A PROBLEM. IF HE CAN GET 10 YEARS OF JUST A NORMAL HAPPY LIFE HE WOULD HAVE BEEN GLAD OF THE LIFE HE HAS HAD. This man shows us how you beat HIV: You don't spread it and you keep your self as healthy as you can, nothing extraordinary just take the meds and stay off the K and cocaine drugs which will destroy you inside out. We still need improvement to have meds taken once a month and this should be done already tomorrow. The science of HIV was complicated with republican politics. Money was withheld but now it is time to floor the gas and get the speed because we see the end of the tunnel. The government of the US has a lot of blood on their hands for ignoring and then cutting benefits to keep on living and for science. Let's do our parts and then we can throw it in their faces where they have failed but first we need to do our part particularly this new young generation. 

Optimal implementation of existing HIV prevention and treatment tools and continued development of new interventions are essential to ending the HIV pandemic, National Institutes of Health experts write in a commentary in Clinical Infectious Diseases.

Today, many highly effectthe ivethe HIV treatment and prevention interventions are available. Antiretroviral therapy (ART) not only improves the health and prolongs the lives of people with HIV but also plays an important role in HIV prevention. People living with HIV whose virus is durably suppressed to undetectable levels by ART cannot sexually transmit HIV to others, a concept known as Undetectable=Untransmittable, or U=U. Antiretroviral drugs taken by people without HIV as pre-exposure prophylaxis (PrEP) are highly effective at preventing the acquisition of HIV.

Theoretically, the widespread provision of ART and PrEP could end the HIV pandemic. However, a gap exists between theory and reality, write Anthony S. Fauci, M.D., director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and colleagues. Implementation gaps exist at all stages of the HIV care continuum. Progress in cities like San Francisco, which has dramatically reduced new HIV cases by deploying ART, PrEP and other tools, suggests that these gaps can be overcome. Such examples offer lessons for optimizing implementation strategies. 

Even with the availability of simplified HIV drug regimens, medication adherence remains a challenge for many. Thus, there is a need to develop new treatment and prevention strategies and products that can be efficiently taken up by people from diverse communities. Potentially, these new tools will have improved efficacy and broader uptake due to better acceptability and usability. 

Researchers are pursuing multiple approaches to achieve durable control of HIV without daily ART, including pursuing a cure that would eradicate HIV from the body or keep it at very low levels, and developing long-acting ART and broadly neutralizing antibodies (bNAbs) that could be dosed once every few months or less often. Approaches to optimizing HIV prevention include long-acting injectables and implants, bNAbs, multi-purpose tools for HIV prevention and contraception, and other innovative strategies. Scientists also are working toward the development of a safe and effective preventive HIV vaccine. Currently, three large HIV vaccine efficacy clinical trials are underway globally.

RW Eisinger, GK Folkers, and AS Fauci. Ending the HIV pandemic: optimizing the prevention and treatment toolkits. Clinical Infectious Diseases DOI: 10.1093/cid/ciz998 (2019).
NIAID Director Anthony S. Fauci, M.D., is available for comment.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets, and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

July 16, 2019:

Today, thanks to remarkable advances in antiretroviral drugs, most people with the human immunodeficiency virus (HIV) can expect to live an almost normal lifespan. But that means staying on medications for life. If those are stopped, HIV comes roaring back in just weeks. Finding a permanent cure for HIV infection, where the virus is completely and permanently eliminated from the body, has proven much tougher. So, I’m encouraged by recent work that shows it may be possible to eliminate HIV in a mouse model, and perhaps—with continued progress—someday we will actually cure HIV in humans.
This innovative approach relies on a one-two punch: drugs and genetic editing. First, HIV-infected mice received an experimental, long-acting form of antiretroviral therapy (ART) that suppresses viral replication. This step cleared the active HIV infection. But more was needed because HIV can “hide” by inserting its DNA into its host’s chromosomes—lying dormant until conditions are right for viral replication. To get at this infectious reservoir, researchers infused the mice with a gene-editing system designed to snip out any HIV DNA still lurking in the genomes of their spleen, bone marrow, lymph nodes, and other cells. The result? Researchers detected no signs of HIV in more than one-third of mice that received the combination treatment.
The new study in Nature Communications is the product of a collaboration between the NIH-funded labs of Howard Gendelman, University of Nebraska Medical Center, Omaha, and Kamel Khalili, Temple University, Philadelphia [1]. A virologist by training, Khalili years ago realized that HIV’s ability to integrate into the genomes of its host’s cells meant that the disease couldn’t be thought of only as a typical viral infection. It had a genetic component too, suggesting that an HIV cure might require a genetic answer. 
At the time, however, the tools to remove HIV DNA from human cells without harming the human genome weren’t available. That’s changed in recent years with the discovery and subsequent development of a very precise gene-editing tool known as CRISPR/Cas9. 
CRISPR/Cas9 editing systems rely on a sequence-specific guide RNA to direct a scissor-like, bacterial enzyme (Cas9) to just the right spot in the genome, where it can be used to cut out, replace, or repair disease-causing mutations. Efforts are underway to apply CRISPR/Cas9 to the treatment of sickle cell diseasemuscular dystrophy, and more. 
Could CRISPR/Cas9 also remove HIV DNA from infected cells and eliminate the infection for good? Such an approach might be particularly helpful for people on ART who have persistent HIV DNA in the cells of their cerebrospinal fluid. A recent NIH-funded study in Journal of Clinical Investigation found that an association between this HIV reservoir and neurocognitive difficulties [2] 
Earlier work by Khalili’s team showed that CRISPR could indeed remove HIV DNA from the genomes of host cells [3]. The problem was that, when delivered on its own, CRISPR couldn’t snip out every last bit of viral DNA from all cells as needed to get rid of HIV completely and permanently. It was crucial to reduce the burden of HIV genomes to the lowest possible level.
Meanwhile, Gendelman’s lab had been working to develop a new and more effective way to deliver ART. Often delivered in combinations, standard ART drugs are effective in suppressing HIV replication. However, people need to take their oral medications daily without fail. Also, most ART triple therapy drugs are water soluble, which means its cocktail of medications are swiftly processed and excreted by the body without reaching many places in the body where HIV hides. 
In his quest to make ART work more effectively with fewer doses, Gendelman’s team altered the chemical composition of antiretroviral medicines, generating fat-soluble drug nanocrystals. The nanocrystals were then packaged into nanoparticles and delivered by intramuscular injection. The new drug formulation, known as long-acting slow-effective release (LASER) ART, reaches lymph nodes, spleen, gut, and brain tissues where HIV lurks [4]. Once there, it’s stored and released slowly over time. Still, like conventional ART, LASER ART can never completely cure HIV. 
So, Gendelman teamed up with Khalili to ask: What would happen if LASER ART was followed by a round of CRISPR/Cas9? In a series of studies, the researchers tested LASER ART and CRISPR/Cas9, both alone and in combination. A total of 23 HIV-infected mice engineered to have some “humanized” immune features received the experimental combination therapy. 
As expected, neither LASER ART nor CRISPR/Cas9 by itself proved sufficient to eradicate HIV in the mice. However, when LASER ART and CRISPR/Cas9 were delivered sequentially, the results were much different. Researchers found no evidence of HIV in the spleens or other tissues of more than one-third of the sequentially treated animals. 
It’s important to note that this gene-editing approach to eradicating HIV is being applied to non-reproductive cells (somatic). The NIH does not support the use of gene-editing technologies in human embryos (germline) [5].
Of course, mice, even with humanized immune systems, are not humans. More research is needed to replicate these findings and to figure out how to make this approach to HIV treatment more effective in animal models before we can consider moving into human clinical trials. Still, these findings do provide a new reason for increased hope that an actual cure may ultimately be found for the tens of millions of people in the United States and around the globe now living with HIV. 
[1] Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice. Dash PK, Kaminski R, Bella R, Su H, Mathews S, Ahooyi TM, Chen C, Mancuso P, Sariyer R, Ferrante P, Donadoni M, Robinson JA, Sillman B, Lin Z, Hilaire JR, Banoub M, Elango M, Gautam N, Mosley RL, Poluektova LY, McMillan J, Bade AN, Gorantla S, Sariyer IK, Burdo TH, Young WB, Amini S, Gordon J, Jacobson JM, Edagwa B, Khalili K, Gendelman HE. Nat Commun. 2019 Jul 2;10(1):2753.
[2] Spudich S et al. Persistent HIV-infected Cells in Cerebrospinal Fluid are Associated with Poorer Neurocognitive Performance. J Clin Invest. 2019. DOI: 10.1172/JCI127413 (2019).
[3] In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models. Yin C, Zhang T, Qu X, Zhang Y, Putatunda R, Xiao X, Li F, Xiao W, Zhao H, Dai S, Qin X, Mo X, Young WB, Khalili K, Hu W. Mol Ther. 2017 May 3;25(5):1168-1186.
[4] Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles. Zhou T, Su H, Dash P, Lin Z, Dyavar Shetty BL, Kocher T, Szlachetka A, Lamberty B, Fox HS, Poluektova L, Gorantla S, McMillan J, Gautam N, Mosley RL, Alnouti Y, Edagwa B, Gendelman HE. Biomaterials. 2018 Jan;151:53-65. 
[5] Statement on Claim of First Gene-Edited Babies by Chinese Researcher. The NIH Director, NIH. 2018 November 28.
HIV/AIDS (National Institute of Allergy and Infectious Diseases/NIH)
HIV Treatment: The Basics (U.S. Department of Health and Human Services)
Fast Facts (HIV.gov)
Global Statistics (HIV.gov)
Kamel Khalili  (Temple University, Philadelphia, PA)
Howard Gendelman  (University of Nebraska Medical Center, Omaha)
NIH Support: National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute of Allergy and Infectious Diseases; National Institute on Aging; National Institute on Drug Abuse; Common  

News posted on the news part of this blog on 04/20/19:


* Researchers-say-single-injection-can-keep HIV at bay for 4 months

How about NOT every day dozing?
The meds for HIV we are using today are so strong that makes us "UNDETECTABLE" and if it doesn't show you can't transmit! They have studies about once a day dozing can be done every other day and the results are promising. Just don't make changes until you speack with your HIV Doctor. If you have a General Practitian make sure he or she are experts on the treatment of HIV.  (Adam, Publisher of Adamfoxie)

No significant differences in viral suppression between groups on daily dosing versus alternate-day dosing of combination fixed-dose tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV, better known with the brand name of Atripla) were found in a randomised clinical trial published in AIDS by Dr Rita Bellagamba and colleagues at the Italian National Institute of Infectious Diseases. 
While levels of efavirenz in plasma concentrations showed a significant decrease in the alternate-day dosing group, this did not significantly affect viral suppression.
Researchers are looking at the possibility of reduced doses of antiretrovirals with long half-lives, such as TDF/FTC/EFV. While efavirenz-based treatment is not as widely used in high-resource settings – due to concerns over neuropsychological symptoms and possible suicidal ideation/suicide – it is still widely used in developing countries, and with pregnant women. 
Previous research included two randomised studies investigating treatment interruption using the FOTO strategy (five days on, two days off) in virally suppressed adults and young people on efavirenz-based treatment. When compared with standard schedules, there were no virological failures at 48 weeks. A proof of concept study looking at reduced dosing of TDF/FTC/EFV to three days a week showed no virological failure at 24 weeks. A recent double-blind, placebo-controlled randomised trialreported that a reduced dose of 400mg EFV was as successful at maintaining an undetectable viral load as the standard dose of 600mg at 48 and 96 weeks. 

HIV+ Undetactable individuals CanNot Transmit to a Negative Sexual partner

You will find different studies and these same headlines for the last two years on this page. That you heard that someone got Hiv from this one or that one is just hearsay. The only information that counts are studies in which the Doctors know everything about the subject and what they are presently doing. That is a study. Taking HIV meds for the HIV+ individual is not enough and many get confused about that little but very important detail. You must show that you are undetectable! This is the cure of HIV we have today and many are not using it. This should have ended stigma but it hasn't because mainly HIV people passing on information that is hearsay. Don't say anything if you re not 100% sure and as always send the person to the right place to get information. Another one: Not all doctors have studied HIV. ASK this page, read it here ask someone involved in HIV with a license. One more thing...How would you know if a person is undetectable? Ask for the latest tests. If he is truly undetectable he is being closely monitored and about every three months, there is a blood test to show where he is in this spectrum. If you are undetectable and don't get or ask or have readily available on your cell phone, etc the latest results where it gives you the number of virus you have, it has to say undetectable or not enough to count. 

Results from a new study presented at the 22nd International AIDS Conference in Amsterdam confirmed something HIV academics have suspected for a long time: The chance of an HIV-positive person with an undetectable viral load transmitting the disease to their partner is “scientifically equivalent to zero.”

These results came from a study known as PARTNER 2, which tracked 635 same-sex couples between May 2014 and April 2018 who were HIV serodiscordant at the start of the study — meaning one was HIV-positive and the other negative — and have condomless sex.

For couples where the HIV-positive person had an undetectable viral load — meaning their drug treatment suppressed the presence of HIV in their blood below 200 copies per milliliter — zero instances of HIV transmission between the couples occurred, according to AIDSmap. These results reinforce the validity of the slogan U = U, meaning “undetectable equals untransmittable.”

“You would have to have condomless sex for at least 420 years to have one incident of HIV transmission,” one researcher said at the conference, per Gay Star News.

The results of PARTNER 1, a study of 888 couples — most of whom were opposite-sex — that concluded in 2014, resulted in similar conclusions about the chance of HIV transmission between serodiscordant couples. However, questions lingered about whether anal sex and vaginal sex would have different chances of HIV transmission. Enter PARTNER 2, which tracked mostly same-sex male couples having condomless anal sex.

Notably, the HIV-negative participants in PARTNER 2 were not taking pre-exposure prophylaxis, a daily pill known as PrEP that reduces the chance of HIV transmission between serodiscordant individuals by more than 90%.

“We looked so hard for transmissions,” principal researcher Alison Rodger told AIDSmap. “And we didn’t find any.”

  • An HIV vaccine tested in animals prompted the immune system to form antibodies that neutralize dozens of HIV strains.
  • A small study of the test vaccine in people is expected to begin in late 2019.
HIV spike and broadly neutralizing antibodiesThis protein structure diagram shows the fusion peptide epitope (red) on the HIV spike (green), which projects out of the viral membrane (grey). Broadly neutralizing antibody (yellow) can bind to the fusion peptide. NIAID
Infection with HIV, the virus that causes AIDS, makes a person vulnerable to many other infections and diseases. So far, researchers have not been able to create an effective HIV vaccine, in part because there are many different strains of the virus.
Some people with HIV infection make antibodies that can neutralize multiple HIV strains. Scientists have studied these antibodies to find clues about how they bind to the virus and neutralize it. Over the past several years, HIV researchers have identified many broadly neutralizing antibodies that can protect human cells in the lab. Scientists examine the sites, or epitopes, on HIV where each known broadly neutralizing antibody binds. They then try to figure out how to make a vaccine based on those epitopes to prompt the immune system to form antibodies. The hope is that these vaccine-induced broadly neutralizing antibodies will protect people from HIV infection.
In 2016, scientists at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) identified an epitope that’s thought to be similar across most HIV strains. Called the HIV fusion peptide, it’s part of the spike on the HIV surface that helps the virus enter a person’s cells. A research team led by Drs. Peter D. Kwong and John R. Mascola of NIAID’s Vaccine Research Center set out to develop an HIV vaccine that targets the HIV fusion peptide. The research was published in Nature Medicine on June 4, 2018.
The research team engineered proteins called immunogens that were designed to activate an immune response against the HIV fusion peptide based on its known structure. The team tested which immunogens most effectively elicited HIV-neutralizing antibodies to the fusion peptide. The best immunogen consisted of eight amino acids of the fusion peptide bonded to a carrier protein often used to boost the immune response.
To improve their results, the team paired this immunogen with a replica of the HIV spike. They tested several vaccine regimens in mice and analyzed the antibodies generated. Antibodies prompted by the vaccines attached to the HIV fusion peptide and neutralized up to 31% of viruses in a panel of 208 HIV strains from around the world.
The researchers used the lessons learned from these experiments and tested modified vaccine regimens in guinea pigs and monkeys. These animals also formed broadly neutralizing antibodies that were active against dozens of HIV strains.
These findings in mice, guinea pigs, and monkeys show that the vaccine regimen can work in several species. The scientists are now working to improve the regimen and test it further in monkeys. A small study of the new vaccine in people is anticipated to begin in late 2019.
“NIH scientists have used their detailed knowledge of the structure of HIV to find an unusual site of vulnerability on the virus and design a novel and potentially powerful vaccine,” says NIAID Director Dr. Anthony S. Fauci. “This elegant study is a potentially important step forward in the ongoing quest to develop a safe and effective HIV vaccine.”

Related Links

References: Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Xu K, Acharya P, Kong R, Cheng C, Chuang GY, Liu K, Louder MK, O'Dell S, Rawi R, Sastry M, Shen CH, Zhang B, Zhou T, Asokan M, Bailer RT, Chambers M, Chen X, Choi CW, Dandey VP, Doria-Rose NA, Druz A, Eng ET, Farney SK, Foulds KE, Geng H, Georgiev IS, Gorman J, Hill KR, Jafari AJ, Kwon YD, Lai YT, Lemmin T, McKee K, Ohr TY, Ou L, Peng D, Rowshan AP, Sheng Z, Todd JP, Tsybovsky Y, Viox EG, Wang Y, Wei H, Yang Y, Zhou AF, Chen R, Yang L, Scorpio DG, McDermott AB, Shapiro L, Carragher B, Potter CS, Mascola JR, Kwong PD. Nat Med. 2018 Jun 4. doi: 10.1038/s41591-018-0042-6. [Epub ahead of print]. PMID: 29867235.
Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID), National Institute of General Medical Sciences (NIGMS), and Office of the Director; Simons Foundation; Empire State Development's Division of Science, Technology, and Innovation (NYSTAR); and Agouron Institute.

Get it from the horse's mouth:

AIDSinfo - Official Site

More: https://adamfoxie.blogspot.com/2018/08/instead-of-keeping-it-like-secret-lets.html

Credit: Nadia Roan, University of California, Berkeley
Researchers have learned a tremendous amount about how the human immunodeficiency virus (HIV),  which causes AIDS, infects immune cells. Much of that information comes from studying immune cells in the bloodstream of HIV-positive people. Less detailed is the picture of how HIV interacts with immune cells inside the lymph nodes, where the virus can hide.
In this image of lymph tissue taken from the neck of a person with uncontrolled HIV infection, you can see areas where HIV is replicating (red) amid a sea of immune cells (blue dots). Areas of greatest HIV replication are associated with a high density of a subtype of human CD4 T-cells (yellow circles) that have been found to be especially susceptible to HIV infection.
This interesting micrograph was among the winners in the University of California, Berkeley  (UC Berkeley) 2017 MIC Image Contest. It comes from the NIH-supported lab of Nadia Roan at the University of California, San Francisco (UCSF) and the J. David Gladstone Institutes, and was generated on a digitizing microscope slide scanner by Rajaa Hussien and imaged by Jen-Yi Lee at UC Berkeley.
The work is part of a larger effort in the Roan lab to understand which subtypes of CD4 T-cells are most vulnerable to HIV infection. Roan’s team initially performed these studies by infecting human cells with HIV in lab dishes. That work has led to some intriguing discoveries. As published recently, Roan and her colleagues identified another subtype of CD4 T-cells, characterized by another cell-surface protein called CD127. These cells allow HIV to enter, but with an unusual twist: once inside the cell, the virus can’t replicate for reasons that remain to be elucidated [1].
As Roan and others continue to learn more about HIV infection in lymph nodes and other types of tissue,  they hope to discover important clues that may lead to new ways to prevent or control the infection. For instance, it might be possible to design treatments to target HIV in parts of the body where the virus likes to hide, and beautiful images like this one are helping researchers to find those hiding places.
[1] Mass Cytometric Analysis of HIV Entry, Replication, and Remodeling in Tissue CD4+ T Cells. Cavrois M, Banerjee T, Mukherjee G, Raman N, Hussien R, Rodriguez BA, Vasquez J, Spitzer MH, Lazarus NH, Jones JJ, Ochsenbauer C, McCune JM, Butcher EC, Arvin AM, Sen N, Greene WC, Roan NR. Cell Rep. 2017 Jul 25;20(4):984-998. 

Undetectable-hiv-means Nontransmittable

 Scanning electromicrograph of an HIV-infected T cell.

What's Next? Viral Eradication.  

In a viral eradication cure scenario, HIV would not only be undetectable in the blood but also would be completely absent from an individual’s body. Viral eradication research is generally expected to require two experimental strategies to be used in conjunction with one another. The first step is to prompt latent HIV to replicate so that the infected cell expresses HIV proteins. The second step involves enhancing the immune system of the person living with HIV or employing other agents to recognize and kill the cells expressing HIV proteins, thereby clearing the latent virus from the body 

In the absence of ART, the vast majority of people living with HIV will eventually develop complications, including AIDS. However, some people living with HIV maintain low levels of virus in the blood—or viral load—even without therapy, indicating that their immune cells are protected from HIV. Other individuals claim to have been exposed to HIV multiple times but have not acquired the virus. Beginning in the late 1990s, studies have revealed that people with stronger natural protection from HIV tend to have mutations in the gene that codes for a protein called CCR5. CCR5 exists on the surface of human immune cells, and HIV uses this protein to enter and infect cells. When CCR5 is dysfunctional or absent because of a defect in the gene that codes for it, HIV no longer has an easy way to infect immune cells. If researchers induce this dysfunction or absence in people born without the genetic mutation, they may be able to help these people better control or eliminate HIV infection. Based on these findings, NIAID funds research exploring how genetic engineering can influence a cure for HIV.
One way clinicians have proposed exploiting natural mutations in CCR5 is through the transplantation of stem cells with this mutation into the bone marrow of an HIV-positive patient, which may lead to a reconstitution of that patient’s immune system with cells that express an advantageous mutation. This method was actually demonstrated in one high-profile case of the Berlin Patient, the only person in history known to experience complete and sustained remission of HIV.
Known as “the Berlin patient” for many years before revealing his identity, Timothy Brown, an HIV-positive American man, was diagnosed with myeloid leukemia while he was living in Germany. Brown’s doctors determined he needed a complete bone marrow transplant, the standard treatment for his life-threatening cancer, and selected a donor who had a CCR5 mutation. Not only did transplantation cure Brown’s leukemia, but for years after the procedure, multiple analyses of Brown’s various bodily tissues revealed no evidence of HIV infection. In 2009, Brown’s physicians reported these findings in the New England Journal of Medicine as a case study funded by the German Research Foundation. While this one patient’s case may hold promise, bone marrow transplants are an intensive procedure that is usually only performed to address serious conditions in the absence of other treatment options. Attempts to replicate these results with bone marrow transplants in other individuals have not yet been successful, primarily because the procedure has only been performed in patients with both HIV and blood cancers, which have a high mortality rate even after bone marrow transplants.
Other recent advancements have opened up the possibility of enhancing the immune system’s ability to fight HIV through gene-editing technologies. Clinicians employing this technique would remove immune cells from an HIV-positive patient, use gene-editing to directly alter the CCR5 gene, and then transfuse the cells back into the individual. In this case, a donor with an advantageous CCR5 mutation is not required, and the patient does not risk life-threatening tissue rejection. Some preliminary research has been done to assess gene-editing as a strategy for both HIV treatment and cure. 
Some clinicians have also proposed using gene-editing technology to directly cut viral genes out of the DNA of latently infected cells. This still theoretical technique would target what is called the HIV provirus. When HIV infects a cell, the virus highjacks the cell’s genetic machinery and inserts its own genome into the cell’s DNA. Advances in biotechnology make it possible for scientists to locate and remove these genes from latent cells using programmed DNA-slicing enzymes. However, scientists still need to understand how to efficiently deliver these gene-editing enzymes to all cells that make up the latent HIV reservoir without causing unintended consequences that may be unhealthy for the patient. Therefore, more research needs to be done to evaluate this approach in living organisms.
 Content last reviewed on March 20, 2017, NIH (National Insitute of Health)

Antibody isolated from people with HIV which can Neutralize Multiple Strains of HIV

Researchers have isolated antibodies from people living with HIV that can neutralize multiple strains of HIV. By studying these broadly neutralizing antibodies, they’ve gained important insights into how the antibodies bind to the virus and why they’re effective. Investigators from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and the pharmaceutical company Sanofi set out to create more potent broadly neutralizing HIV antibodies. The team was led by Dr. John R. Mascola, director of the NIAID Vaccine Research Center, and Dr. Gary J. Nabel, Sanofi chief scientific officer and senior vice president. The work appeared online in Science on September 20, 2017.

The researchers combined portions of individual broadly neutralizing antibodies to engineer a series of antibodies in the laboratory. They created dozens of “bispecific” (binding to two different sites on the virus) and “trispecific” (binding to three different sites) antibodies. Testing revealed the most successful to be a trispecific antibody that combined parts of the broadly neutralizing HIV antibodies VRC01, PGDM1400, and 10E8v4. This single engineered molecule interacts with three independent parts of the HIV surface.

Infusions of the three-pronged antibody completely protected eight monkeys from infection with two strains of SHIV, a monkey form of HIV. In contrast, infusions of the individual antibodies from which the engineered antibody was derived were only partially protective. The trispecific antibody also prevented a broader range of HIV strains from infecting cells in the laboratory.

Sanofi is manufacturing the trispecific antibody for use in a Phase 1 clinical trial that NIAID is planning to conduct. The trial will test the antibody’s safety and effects in healthy people beginning in late 2018. Discussions also are under way for a separate Phase 1 clinical trial of the antibody in people living with HIV.

“Combinations of antibodies that each bind to a distinct site on HIV may best overcome the defenses of the virus in the effort to achieve effective antibody-based treatment and prevention,” says NIAID Director Dr. Anthony S. Fauci. “The concept of having a single antibody that binds to three unique sites on HIV is certainly an intriguing approach for investigators to pursue.”

The ability of trispecific antibodies to bind to three independent targets could make them useful for other types of treatments as well. Other potential targets include infectious diseases and cancers.

July20:  Meds Resistance Can Undermine HIV Battle

- Rising levels of resistance to HIV drugs could undermine promising progress against the global AIDS epidemic if effective action is not taken early, the World Health Organization (WHO) said on Thursday.

Already in six out of 11 countries surveyed in Africa, Asia and Latin America for a WHO-led report, researchers found that more than 10 percent of HIV patients starting antiretroviral drugs had a strain resistant to the most widely-used medicines.

Once a threshold of 10 percent is reached, the WHO recommends countries urgently review their HIV treatment programs and switch to different drug regimens to limit the spread of resistance.

HIV drug resistance develops when patients do not stick to a prescribed treatment plan - often because they do not have consistent access to proper HIV treatment and care.

Patients with HIV drug resistance start to see their treatment failing, with levels of HIV in their blood rising, and they risk passing on drug-resistant strains to others.

The WHO's warning comes as the latest data from UNAIDS showed encouraging progress against the worldwide HIV/AIDS epidemic, with deaths rates falling and treatment rates rising.

Some 36.7 million people around the world are infected with HIV, but more than half of them - 19.5 million - are getting the antiretroviral therapy medicines they need to suppress the HIV virus and keep their disease in check.

The WHO said, however, that rising HIV drug resistance trends could lead to more infections and deaths.

Mathematical modeling shows an additional 135,000 deaths and 105,000 new infections could follow in the next five years if no action is taken, and HIV treatment costs could increase by an extra $650 million during this time.

"We need to ensure that people who start treatment can stay on effective treatment, to prevent the emergence of HIV drug resistance," said Gottfried Hirnschall, director of the WHO's HIV and hepatitis program.

"When levels of HIV drug resistance become high we recommend that countries shift to an alternative first-line therapy for those... starting treatment."

The WHO said it was issuing new guidance for countries on HIV drug resistance to help them act early against it. These included guidelines on how to improve the quality and consistency of treatment programs and how to transition to new HIV treatments, if and when they are needed.

(by Kate Kelland, editing by Pritha Sarkar for Reuters)

Genetic Truvada Approved by FDA

 In a move that has taken HIV advocates by considerable surprise, the U.S. Food and Drug Administration (FDA) has approved a generic formulation of Gilead Sciences’ blockbuster antiretroviral (ARV) Truvada (tenofovir disoproxil fumarate/emtricitabine). This decision could have major implications for the future cost of Truvada, to insurers and consumers alike.

The approval, which grants Teva Pharmaceuticals the right to produce generic Truvada, is for the combination tablet’s use as a component of an HIV treatment regimen and as pre-exposure prophylaxis (PrEP). Generic Truvada will come in the same form as the brand-name version: as a fixed-dose combination tablet, although the famous powder-blue color may change.
“Yes, the first generic for Truvada has been approved and will now be available in the U.S.,” Jeffrey S. Murray, MD, MPH, deputy director of the Division of Anti-Viral Products at the FDA, tells POZ. “Usually, it takes several generics before full cost-savings potential is reached though. Hopefully, this will help to expand PrEP availability for many.”

According to Murray, it remains unclear what sort of exclusivity Teva may have to produce generic Truvada. Generic manufacturers often hold such exclusive rights for an initial period before competitors can also begin producing a particular generic medication and thus drive down prices. Murray stated that clarity on Teva's rights in this regard may not come for several months.
A Teva spokesperson confirmed the generic Truvada approval, but said that no further related information was available at this time.

“While this is stunning news that AIDS activists didn’t expect until 2021, I’m worried about the fallout,” says ACT UP and Treatment Action Group veteran Peter Staley. “Gilead’s patient and copay assistance programs have become central pillars in patient access. They must maintain these programs, and Teva must establish equivalent or better assistance programs for their generic version.”
More information on the implications of this approval is to come. Check this link later for updated information.

Condom-less Sex: A Doctor’s opinion

Large numbers of gay men engage in sex without condoms, so earlier this spring, Hornet — the world’s premier gay social network, and also the parent company of this site — held a panel conversation entitled “Gay Sex: A Raw Conversation” with a porn star, HIV activists and Dr. Demetre Daskalakis, a medical doctor working with the New York City Department of Health and Mental Hygiene and also the star of the Here TV program The T with Dr. D.
Hornet Senior Health Innovation Strategist Alex Garner caught up with Daskalakis after the event to ask his professional opinions about condomless sex, gay and bi men’s sexual health and the effects sexual health has on mental health.
What do you think condomless sex means in regards to sexual health?
Condomless sex is a reality of our scenario in 2017. Some people use condoms every time. Many others are inconsistent or don’t use them at all. From the sexual health perspective, the message is to use condoms as often as possible, ideally every time; but, if you can’t or won’t use condoms, then take daily PrEP or HIV treatment depending on your status to keep yourself and your partners healthy. No matter which strategy you choose, getting tested for STIs (including HIV) every three months is critical to identifying and treating any infections early.
Our relationship to sex without condoms is heavily impacted by our history. How would you describe your relationship to the epidemic?
I lived through the bad old days when we had few meds, complications, and sex was being equated to death. I feel privileged to be part of a renaissance of sexual health that focuses on HIV less and on sexual health, in general, more.
What impact does condomless sex have on gay men’s mental health?
That’s a complex question. For some, condoms are just a part of their reality; for others, they represent a barrier to intimacy. I think that different men have different relationships to condoms. For some, condoms remove anxiety; for others, they add to it. It’s really about acknowledging the diversity of feelings and offering strategies to prevent HIV and STIs that respect these feelings.
What have you found to be the best strategy to reduce STIs if having condomless sex?
Test and treat! Men having condomless sex should get tested for HIV (if they are negative), syphilis, and gonorrhea and chlamydia from their throats, butts and urine/penis at least every three months.  Early detection and treatment leads to better control of STIs in the long term!
Public health often views condomless sex as a pathology, but how might choosing to pursue pleasure and intimacy actually be resiliency?
I feel that — at least in New York City — we do not pathologize condomless sex. We encourage people to live a full life that includes strategies that minimize risk of infection while maximizing their pleasure and intimacy goals.  Like I say, the epidemic of HIV can only end with love, not stigma or guilt.  People need to live their truth but do so with eyes open to maintain both health and pleasure.

The first official updates of HIV incidence estimates in several years.
On February 14, 2017, the U.S. Centers for Disease Control and Prevention (CDC) unveiled new HIV incidence estimates for the United States from the years 2008 through 2014. Employing a recently developed method for estimating HIV incidence (based on diagnostic and CD4 cell level at time of diagnosis information), CDC provided the first official updates of HIV incidence estimates in several years.
This new methodology and updated estimates are very welcome and will better help address the epidemic in the United States, since timely incidence estimates (previous estimates were for the year 2010) are key to understanding the dynamics of the U.S. epidemic and are an essential component to any national statistical dashboard for up-to-date monitoring of the HIV epidemic. 
CDC reported that between 2008 and 2014, HIV incidence declined by 18 percent in the United States. However, several key disparities are apparent. In 2014, Southern states comprised about one-half of new HIV infections, and gay and bisexual men accounted for approximately 70 percent of new HIV infections. Additionally, incidence did not decline for Black gay and bisexual men over this time frame. Further, incidence increased among Latino gay and bisexual men and also increased among gay and bisexual men ages 25 to 34. 
While the overall 18 percent decline from 2008 to 2014 is welcome news, we must not celebrate too quickly. In order to understand the magnitude and meaning of an 18 percent decline in any public health metric, we must compare it to previously set national goals. The National HIV/AIDS Strategy (NHAS) set forth by President Obama’s administration in 2010 called for a 25 percent reduction in HIV incidence by 2015. Did we make it?
CDC estimates that HIV incidence in 2010 was 41,600; in 2014 it was 37,600. This decline of approximately 4,000 new HIV infections through 2014 reflects a roughly 9.6 percent drop; less than halfway to the national goal of 25 percent reduction by 2015 (though future updates from CDC for HIV incidence in 2015 will be important to monitor in this regard).
This 9.6 percent drop from 2010 through 2014 is similar to a 9.1 percent estimate we published last year using a somewhat different methodology; in our previous paper, we modeled incidence for 2015 as well and estimated that from 2010 through 2015, HIV incidence in the United States is likely to have dropped roughly 11.1 percent
Both our previous modeling efforts and CDC’s new HIV incidence estimates suggest that from 2010 through 2015, HIV incidence declined in the United States, but made it not even halfway to the 25 percent reduction goal. This important point alerts us to the fact that HIV prevention, care and supportive housing efforts in the United States are still not at the scale necessary to meet the original NHAS goals.
At a time when some decision makers are considering possibly repealing and/or replacing the Affordable Care Act, which we know provided critical health insurance access for persons living with HIV and helped to avoid HIV transmission, we should instead be focusing as a nation on expanding critical HIV-related services and access to comprehensive care. The NHAS provides a clear roadmap in this regard. 
Further, the health disparities, especially for gay and bisexual men of color and gay and bisexual men in young adulthood, are clearly unacceptable and must be addressed with culturally relevant, evidence-based, comprehensive wellness services that address HIV and health in a holistic manner.
The same is true for the disparities seen in the Southern United States; this unequal geographic impact of the epidemic, which is mirrored by the burden of other diseases such as diabetes and heart disease, has been known for far too long for such disparities to continue to exist.
These inequities challenge us to once again recommit ourselves to addressing critical social determinants of public health, such as stable housing, food security, affordable health care, and non-stigmatizing health care delivery systems (among other key social determinants). 
We believe that it is important to continue to keep our eyes squarely on well-articulated national HIV-related goals, and to make the requisite financial and resource investments to scale up evidence-based prevention and care services to reach the goals.
With 2015 in the rearview mirror, we argued last summer in this forum that by 2020, HIV incidence could decline to 23,000 if 90 percent of persons living with HIV were diagnosed, 90 percent of diagnosed persons were linked to and retained in quality care services, and 90 percent of persons in care achieved viral suppression, goals consistent with the updated NHAS. While the nation is inching closer to 90 percent awareness that one is living with HIV, we have much work to do to achieve the retention in quality care and viral suppression goals. 
That more work remains should not hinder our cause, but instead motivate us to strive for such milestones. As President Obama said when he released the first NHAS in July 2010 at the White House, “The question is not whether we know what to do, but whether we will do it.” For our communities most heavily and disproportionately impacted by HIV and for all our loved ones whose lives have been lost to HIV, we say that we must do it.
David Holtgrave, PhD, is a professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore and chair of the department of health, behavior and society. Robert Bonacci, MD, MPH, is a resident physician of the department of medicine at Brigham and Women’s Hospital in Boston. The views stated in this post are those of the authors and do not necessarily express the position or views of their employers. This article was originally published on The Huffington Post.

Growing Old with HIV after Decades of Treatment

The success of breakthrough HIV drugs means one of the biggest challenges in the decades to come will be treating HIV as part of the aging process. More than half of all people with HIV in the United States are over 50, and by 2030 it is estimated that this figure will rise to 70 percent, according to the International Society for Infectious Diseases. Older HIV patients will be in general decline, while also battling conditions caused by decades of HIV drug use.

"This is a new frontier for a lot of us," said Kelsey Louie, chief executive officer at nonprofit Gay Men's Health Crisis. "People are living longer with HIV, so we are dealing with things we haven't had to deal with before, like the long-term effects of medication," he said. "It's important to understand that people who are aging will be facing other health issues that will only be complicated by HIV."

The economic toll of HIV in the U.S. keeps rising. This year federal funding for the disease has reached $27.5 billion. Today there are more than 1.2 million people in the United States living with HIV. More than 700,000 people with AIDS have died since the beginning of the crisis, according to data compiled by the Centers for Disease Control and Prevention. In 2014, there were 12,333 deaths (due to any cause) of people with diagnosed HIV infection ever classified as AIDS, and 6,721 deaths were attributed directly to HIV, according to the CDC. Doctors and drug companies are pursuing new approaches to treatment.

"We are at a fork in the road," said Greg Millet, vice president and director of public policy at AIDS nonprofit amfAR, who previously worked on AIDS and aging as a government epidemiologist during the Obama administration. "The fact that people living with HIV are living longer is fantastic news for many of us coming up in the era of the '80s and '90s, when it was effectively a death sentence and people did not live beyond five to 10 years," he said.

"When you are taking care of patients for their life, you don't want to only be able to offer them just one medicine. ...  You have to take a long view and be able to switch medications whenever necessary."
-John Pottage Jr., chief scientific and medical officer at ViiV Healthcare
Eric Sawyer, age 62, a long-term HIV activist and consultant at the New York City-based GMHC, knows all too well the toll that these lifesaving medications can take on the body. Sawyer started developing symptoms of HIV back in 1981, even before the virus was discovered. At the time, he was told that he wouldn't live to see age 35. Fortunately, he was able to enroll in some of the earliest clinical trials taking place in HIV medical research. He has taken part in testing for a host of HIV drugs over the years.

While these drugs helped save Sawyer's life, some of the drugs he took came with debilitating side effects. One drug played a role in his developing peripheral neuropathy, which causes severe pain in his feet. To this day, Sawyer can't wear regular shoes. Years later Sawyer developed avascular necrosis of the hip. "My hip started to crumble, and I had to have a hip replacement in my 40s and the other hip replaced a couple of years ago."

The development of this type of necrosis can arise from the use of anabolic steroids that physicians often prescribe to people living with HIV to help them to gain weight, or from medications currently being prescribed to treat the disease, said Dr. Bisher Akil, a New York City-based physician who treats Sawyer.

About five years ago Akil started Sawyer on an antiretroviral medication called Truvada, developed by Gilead Sciences. Today's HIV antiretroviral drug regimens are taken in pill form, as part of a three-drug treatment regime that work together as a cocktail to block the HIV-virus at different parts of the replication cycle. This approach stops the virus from infecting new cells and allows a patient's T-cell count to replenish. These drugs have proven so successful they can reduce the amount of the HIV virus detectable in the body to a degree that it is no longer measurable by a blood test.

Truvada worked well for Sawyer, but the medication may also have played a role in causing a severe level of toxicity in his kidneys, which left untreated can result in renal failure. To stop the elevation of serum creatinine levels in Sawyer's blood, which was causing damage to his kidneys, Akil took Sawyer off Truvada and replaced it with Gilead's newer version of the drug, Descovy, which received the Food and Drug Administration's approval in April 2016.

Descovy, a combination of the drugs emtricitabine and tenofovir alafenamide (TAF), can be given at a much lower dose than Truvada. Several of Gilead's newer HIV drug therapies, such as Genvoya and Odefsey, contain TAF in place of tenofovir disoproxil fumarate (TDF), which is the main ingredient in Gilead's older HIV drugs — Stribild, Atripla and Complera, as well as Truvada.

TAF has demonstrated that it works as well as TDF-based drugs at less than one-tenth the dosage. It has also demonstrated improvements in renal and bone safety. Patients in a trial on a TAF-based drug had less hip and spine bone loss and more favorable kidney function than those on TDF-based drugs, according to Gilead.

Descovy has an average wholesale price of near-$1,800 a month, similar to Truvada's price, according to pricing information from the National Institutes of Health. Sawyer's doctor said paying for Descovy would be cheaper for the health insurance provider than paying for Sawyer to go on dialysis or get a kidney transplant, which is where Sawyer was headed. After six months on Descovy, Sawyer's kidney function improved.

This switch to newer drugs is beginning to show up in Gilead's results. In its quarterly earnings released last week, overall HIV drug sales increased by 12 percent, to $3.4 billion, in the fourth quarter 2016, even as Truvada sales and sales of other, older TDF-based HIV drugs continued to decline. HIV sales totaled $12.9 billion for the full year 2016, also up from the previous year's level of $11.1 billion.

Accelerated aging

AmfAR's Millet said HIV and related drug therapies have been shown to accelerate the aging process with issues including the onset of kidney and liver disease, bone loss and osteoporosis and cognitive impairment.

"We need to start focusing on these other issues. … There is not enough medical literature on common geriatric drugs and HIV drugs," he said. Millet added that the issue is not only whether HIV drugs and other geriatric drugs could interact negatively but whether other drugs could suppress the HIV drug regimen. There is also evidence that HIV-positive individuals develop an immune system that is described as "hyper vigilant" for an extended period of time, and in older people that can lead to chronic inflammatory conditions.

ViiV Healthcare is close to releasing new HIV medications that could do less harm to older HIV patients by replace the three- and four-drug "cocktail" many HIV patients are on with a two-drug therapy. The UK-based joint venture of Pfizer, GlaxoSmithKline and Japan's Shionogi & Co. released Phase III clinical trial results this week for one of its new two-drug therapies.

John Pottage Jr., chief scientific and medical officer at ViiV Healthcare, said two drugs is the lowest number needed to inhibit the virus at different parts of its replication cycle. "If you are thinking about patient care over the long term, you want to be able to individualize the care of patients and provide for future options that may come with less side effects," he said. A two-drug therapy may do just that. "It goes back to having choices for patients," Pottage said.

 UNAIDS: We're making progress but prevention is still a challenge UNAIDS: We're making progress but prevention still a challenge
Wednesday, 30 Nov 2016 | 9:06 PM ET | 02:21
Pottage said the prognosis for these new therapies is promising and the company expects to file with the FDA for approval in mid-2017. If all goes well, ViiV Healthcare will bring at least one two-drug HIV-treatment combinations to market in 2018, per FDA approval. The company will be filing in other countries and regions around the world as well.

ViiV is also working with Johnson & Johnson's Janssen to develop a once-a-month injection for patients who have already achieved HIV-viral suppression through a daily pill regimen.The injectables would be given as an intramuscular shot that releases the medication out into the body over a period of time, a dramatic change in the way antiretroviral treatment is administered. The pharma company has started a Phase III trial and will evaluate the data in 2018 with the hope of submitting it for FDA approval in 2019.

Global sales of HIV therapies reach into the tens of billions of dollars.

Competition between drug developers remains fierce, but Pottage said that all new discoveries are welcome, in particular by physicians. "When you are taking care of patients for their life, you don't want to only be able to offer them just one medicine. You may need to change the medications and dosage to see which drugs are more tolerable," Pottage said. "You have to take a long view, and be able to switch medications, whenever necessary."

Millet agreed. "Providing choices of drugs is one of the best ways to suit what is best for patients," he said. For some that may be to continue taking a daily dosage of pills. But cognitive impairment could make it more difficult for older HIV patients to manage their prescriptions, creating a need for a delivery option, like injectables.

The young and the old

Millet said research into long-term injectables would help the HIV population on both ends of the demographic curve: the youngest HIV-positive individuals are by far the largest group of new cases, as well as undiagnosed cases.

The annual number of new HIV diagnoses in the United States from 2005 to 2014 declined by 19 percent, but as many as 50,000 new cases are diagnosed each year, according to CDC data. Thirty-seven percent of new HIV cases in 2015 were among people age 13 to 19, according to the CDC. Sixty-three percent of new HIV cases are among individuals 29 years or younger.

"This would be very helpful for young people, as they are less likely to adhere to medication," Millet said. It would not only help young HIV patients to suppress the virus but would reduce the number of new cases. Millet said there is also ongoing research into HIV drug implants, which could function similar to birth control and work for as long as a year.

"Younger individuals did not experience the period of the HIV epidemic in which people with HIV were dying in great numbers due to a lack of treatment options. This can make it difficult to communicate the urgency of HIV prevention efforts."
-Dr. Demetre Daskalakis, assistant commissioner of the Bureau of HIV/AIDS Prevention and Control at the NYC Health Department Control
In New York City the number of new HIV diagnoses has decreased in all age groups over the past five years, and that means that everyone living with HIV is living longer, said Dr. Demetre Daskalakis, assistant commissioner of the Bureau of HIV/AIDS Prevention and Control at the NYC Health Department.

"The overall epidemic is aging because of population dynamics," Demetre said, but he added that new HIV diagnoses are indeed concentrated among young persons. In 2015, 36 percent and 26 percent of new diagnoses in New York City were among persons age 20 to 29 and 30 to 39, respectively.

Younger individuals "are still the leading edge of the epidemic – where the most sexual activity is taking place and where the lowest levels of viral suppression have been achieved," he said. Sixty-six percent of all persons 20 to 29 are virally suppressed, whereas 86 percent of persons over the age of 60 are virally suppressed.

"These factors create the 'perfect storm' for the ongoing epidemic among younger persons," Demetre said. "Younger individuals did not experience the period of the HIV epidemic in which people with HIV were dying in great numbers due to a lack of treatment options. This can make it difficult to communicate the urgency of HIV prevention efforts."

"Long-term injectables are incredibly promising," Millet said. But he stressed one point about current HIV drugs that should not be lost as research into new drugs proceeds: "The first-line medication are easily the best ever. These are remarkably effective, with very few side effects."

— By Leslie Kramer, special to CNBC.com

The Other Brain in HIV  Infection (the other brain refers to the Gut) 

University of Alabama at Birmingham
Using a novel technique to analyze antibodies in fluid collected from intestines of 81 HIV-1-infected and 25 control individuals, researchers have found abnormal gut antibody levels in people infected with HIV- 

The barrier between the gut and the bloodstream is severely damaged in the first few weeks of infection by HIV-1 virus. This can allow whole microbes in the intestine, as well as tiny pieces of bacteria, to enter the blood and provoke the inflammation that can lead to AIDS -- even when replication of the virus is controlled by drug therapy.
Using a novel technique to analyze antibodies in fluid collected from intestines of 81 HIV-1-infected and 25 control individuals, University of Alabama at Birmingham researchers have found abnormal gut antibody levels in people infected with HIV-1. This antibody dysregulation, they say, may be an important factor contributing to the failure of the gut to prevent the inflammatory microbial invasion of the bloodstream.
The researchers, led by Zdenek Hel, Ph.D., associate professor in the UAB Department of Pathology, used a technique called protein microarray analysis. A total of 39 different protein antigens from gut bacteria -- antigens that are known to elicit antibody immune responses in humans against those antigens -- were used to bind antibodies from gut wash fluid. A variety of food antigen proteins were also used to bind antibodies. Researchers then could test what types of antibodies were produced in HIV-1-positive and HIV-1-negative subjects.
Hel and colleagues found that both infected and uninfected subjects made antibodies against these bacterial and food antigens. However, the two groups differed greatly in the types of antibodies produced.
People with HIV-1 had higher proportions of a less mature form of antibody called immunoglobulin M, or IgM, as compared with the antibody forms called IgG and IgA that are better at binding antigens. This suggests that immune system cells in the inner layer of the intestine, the mucosa, are unable to make the types of antibodies needed to prevent bacterial fragments from entering the bloodstream.
Further, the researchers say, accumulation of IgM in the gut mucosa may form immune complexes that exacerbate inflammation.
It is well-known that antibody-producing cells switch from early production of IgM to later production of IgG and IgA in people with healthy immune systems. It is also well-understood that HIV-1 infections cause early and profound depletion of the immune memory cells in the mucosa that are indispensable for that immune-type switching.
Hel's finding that HIV-1 infection is associated with significant elevation of IgM levels and decreased ratios of IgG/IgM and IgA/IgM is consistent with the loss of those mucosal memory CD4+ T cells.
"This study involved a relatively small number of patients and did not include direct analysis of intestinal tract cells," Hel said. "Nonetheless, the findings could improve our understanding of how HIV-1 undermines the immune system and inform research into potential new treatments."
The paper, "Dysregulation of systemic and mucosal humoral responses to microbial and food antigens as a factor contributing to microbial translocation and chronic inflammation in HIV-1 infection," is published in PLOS Pathogens.

Story Source:
Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.

Journal Reference:

  1. Zdenek Hel, Jun Xu, Warren L. Denning, E. Scott Helton, Richard P. H. Huijbregts, Sonya L. Heath, E. Turner Overton, Benjamin S. Christmann, Charles O. Elson, Paul A. Goepfert, Jiri Mestecky. Dysregulation of Systemic and Mucosal Humoral Responses to Microbial and Food Antigens as a Factor Contributing to Microbial Translocation and Chronic Inflammation in HIV-1 Infection. PLOS Pathogens, 2017; 13 (1): e1006087 DOI: 10.1371/journal.ppat.1006087

If you are Undetectable and have been for a year non stop then you should feel free. I understand for some only a blood test that says “cured” would be the only thing to make them feel free but things particularly in medicine with an ever mutating virus do not tend to go by those rules. You need to be informed. The following is a story of a man that went through all the cycles an HIV person goes through but then felt free after being Undetectable:

Fourth of July: In the U.S., it's a day to wave the flag and tell the story of American freedom at cookouts, with cold drinks and sweets.
For Bruce Richman, 47, of Brooklyn, this year's July 4th was a different kind of Independence Day, calling for a different kind of party. It marked six years with an undetectable viral load -- a status he couldn't have imagined when he was diagnosed in 2003 or when he was in the hospital in 2010 with opportunistic infectionsassociated with AIDS. And it certainly wasn't a status he could have imagined during all his years of social and romantic isolation, when he felt that his body was toxic and he had to protect others from it.
Today, to Richman, an undetectable viral load means freedom -- emotional freedom from self-condemning voices, but also freedom to love, freedom to give himself the intimacy he's craved since before his HIV diagnosis. That one word, "undetectable," was the permission he needed to love again. So on the day many were celebrating another kind of freedom, he celebrated his personal freedom with his new boyfriend, his best friends and a cake festooned with a big, red U for undetectable. To Richman, this celebration was no less revolutionary.
"I'm at a place where I've spent 13 years with HIV, but it no longer stands between me and someone I love," he said. "Undetectable is something monumental in the history of HIV. To be able to become uninfectious to others — it's a reason to celebrate, a reason to party!"

Who can a zeroNegative guy be safe with? Discordant partners can feel so much better with what we’ve known about meds and becoming undetectable:

HIV-positive people with a viral load below 200 copies/mL while on antiretroviral therapy (ART) did not transmit HIV to steady sex partners during more than one year of condomless sex in the European PARTNER Study. Eleven HIV-negative partners, including 10 men who have sex with men (MSM), did become infected during follow-up, but phylogenetic analysis did not link the infecting virus to their on-treatment partner. Confidence limits and short follow-up so far suggest, however, that "appreciable levels of risk cannot be excluded."

HPTN 052 and other studies showed that HIV-positive people with ART-suppressed viremia have an exceedingly low risk of transmitting HIV to their sex partners. To determine transmission risk from virally suppressed HIV-positive European partners having vaginal or anal sex, the PARTNER Study Group conducted this prospective observational analysis.

From September 2010 to May 2014, researchers recruited HIV-discordant partners (one HIV-positive, one negative) at 75 clinical sites in 14 European countries. To be included in the transmission analysis, partners had to report (1) condoles vaginal or anal sex in the months before enrollment, (2) continued condomless sex during the study period, (3) no use of pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) and (4) latest viral load in initially positive partner below 200 copies/mL on ART. 

Negative partners were tested for HIV infection every 6 to 12 months, while positive partners had their viral loads tested at the same intervals. If a negative partner acquired HIV infection, viral pol and env sequences from both partners were tested to determine whether the partners' HIV was genetically related.

The transmission analysis involved 888 couples, including 548 heterosexual couples and 340 MSM couples. Among heterosexual couples, 279 (51%) had an HIV-positive female partner and 269 a positive male partner. Median ages of MSM and heterosexual men and women ranged from 40.1 to 44.9 years. About 80% of participants were white. Median follow-up measured 1.3 years per couple and overall follow-up totaled 1238 couple-years. Among HIV-negative partners, MSM reported a median of 42 condomless sex acts per year, heterosexual men reported 35 and heterosexual women reported 36.

During follow-up, 11 initially negative partners acquired HIV infection, including 10 MSM and one heterosexual. Eight of these 11 people reported recent condomless sex with someone other than their regular partner. HIV sequence analysis found no evidence indicating that newly infected partners acquired HIV from their study partner.

HIV transmission rate from positive to initially negative partners was 0 for MSM and for heterosexual men and women. The rate was 0 for vaginal sex, insertive anal sex and receptive anal sex with ejaculation. Upper 95% confidence limits for certain subgroups were higher than the overall upper 95% confidence limit of 0.30 per 100 couple-years for any sex, for example, receptive anal sex with ejaculation in MSM (2.70) or heterosexual women (12.71) and insertive anal sex in heterosexual men (7.85).

Although the transmission rate for vaginal or anal sex was 0, the PARTNERS investigators cautioned that "95% confidence limits suggest that with eligible couple-years accrued so far, appreciable levels of risk cannot be excluded." The researchers stressed that their results "cannot directly provide an answer to the question of whether it is safe for serodifferent couples to practice condomless sex."

Still, despite the median follow-up of 1.3 years per couple, the authors noted that their analysis "contains more than 3 times the couple-years of follow-up for condomless sex than all the other previous studies combined, including more than 500 couple-years of follow-up of condomless anal sex."

Mark Mascolini writes about HIV infection, {The Body}

No Proof of New HIV Cure, Despite Headlines -- Here's What We Know

Whenever you see a newspaper headline about a cure for HIV, it's worth treating it with a pinch of salt. That's certainly the case with the latest story, first reported by The Sunday Times of London and repeated in media outlets around the world.

Many people living with HIV desperately want to see a cure for HIV. Millions of other people would be fascinated and encouraged to see such scientific progress. Journalists know this, which is why they so often fall into the trap of writing stories that suggest a cure is just around the corner. The idea fills us with hope, and huge numbers of people will click on the story to find out more.

The mainstream media tends to report these issues in a misleading way or leave out key details that would help people living with HIV understand what the developments mean for them. Important and legitimate scientific studies are misrepresented.

What's the New Story About a Cure?

The headlines tell us "British Scientists on Brink of HIV Cure," "HIV Cure Close After Disease 'Vanishes' From Blood of British Man" and "British Man Becomes the First Patient Cured of HIV."

The reports suggest that the man took an experimental treatment and now the scientists cannot find a trace of HIV in his body. That suggestion is wrong. Here's what really happened.

He was diagnosed within six months of infection and took an intensive treatment regimen -- four antiretrovirals, a drug called vorinostat and two vaccines.

Several months after beginning his treatment, tests can't detect HIV in his blood. In other words, his viral load result is undetectable. This may sound remarkable and astonishing to some journalists, but people with HIV will know that this is exactly the result we expect after several months of antiretroviral therapy.

Remember, this man's treatment includes antiretroviral therapy, the same drugs used by other people living with HIV. He took other, innovative treatments as well, but his antiretroviral therapy alone could be expected to bring his viral load down to an undetectable level.

And, very importantly, he is still taking antiretroviral therapy. Nobody knows what will happen if he ever decides to stop taking his treatment.

What Do We Know About the Study?

The man is taking part in a serious clinical trial that is investigating an innovative approach to treating HIV. Researchers at five leading British universities are conducting it.

The scientists hope their aggressive treatment will eradicate latent reservoirs of HIV in the body. Reservoirs are made up of millions of immune system cells that contain dormant HIV. They persist even when antiretroviral treatment reduces viral load (RNA) to undetectable levels -- but would be re-activated if antiretroviral treatment were stopped.

Around 50 people who have had HIV for less than six months will take part in the study. They will all take an intensive combination of antiretroviral therapy (four drugs, including Isentress [raltegravir]).

In addition, half the participants will be randomly assigned to take the innovative treatments. For one month, they will be given vorinostat, a drug that forces the virus to emerge from hiding places in the body. They will also receive two vaccines that aim to boost the immune system so that it can attack HIV-infected cells. The strategy is called "kick and kill."

Ten months after study participants enter the trial, the researchers will measure levels of HIV DNA in CD4 cells. This will provide an indication of whether the treatment has had an impact on the HIV reservoir.

The unnamed man who has been the focus of the media attention is simply the first study participant to have completed the experimental therapy. The researchers report that the treatment was safe for him. In a brief statement they released on Oct. 3, the researchers themselves note that results of the study will not be reported until 2018, and that until then, "We cannot yet state whether any individual has responded to the intervention or been cured."

Questions and Answers

‘What about the other people taking part in the study?

‘Only 39 of about 50 participants have been recruited so far. We don't know anything else about the other participants.

‘Do tests show that this man's viral reservoir has been eliminated?

‘We don't know; the scientists will only report this information when the trial is completed in 2018.

‘How would we know that someone is cured of HIV?

‘Antiretroviral therapy would have to be stopped and the person monitored for several years. Researchers would check to confirm that either that there was no trace of HIV in any cells or the person's immune system could keep HIV under control without treatment.

‘Will people in this trial stop their antiretroviral therapy?

‘This is not part of the study. The researchers may explore this option in the future but are not recommending it for now.

‘Has anything like this been tried before?

‘Slightly different "kick and kill" approaches have been tried in other studies. And there have been examples of people taking intensive treatment very soon after infection, continuing with it for several years, then stopping treatment and remaining undetectable.

‘Has anyone been cured of HIV?

‘To date, there is only one confirmed case of an HIV cure. Timothy Ray Brown, who needed treatment for advanced leukemia, received a never-before-attempted stem cell transplant in which the donor had a rare mutation making him essentially immune to most forms of HIV.

Does Undetectable means Un-infectious? 

As the executive director and cofounder of Prevention Access Campaign (PAC), Bruce Richman focuses on getting the word out about the benefits of HIV treatment not only for people living with the virus but also for their sexual partners—specifically, he’s focused on the ways that meds can prevent the spread of HIV.

To further his activism, Richman has launched a POZ Blog. Check out his inaugural post, “Loud and Clear: Undetectable = Uninfectious,” to learn how feelings of fear and anxiety about his HIV diagnosis gave way to a sense of freedom once he realized that having an undetectable viral load meant he wasn’t a danger to his partner.

While we were setting up the blog, POZ reported on findings from the PARTNER study, which further supports HIV treatment as prevention (TasP). Richman voiced his concerns about the article and the cautionary tone of the study’s accompanying editorial and press release, which he felt should have been more celebratory. As we discussed the challenges of explaining and interpreting study results about HIV transmission risk, we both realized it was an important conversation worth sharing.

Below is part of our email exchange, edited for clarity and length.
Bruce, thanks for talking about the PARTNER trial results, which were presented at the 21st International AIDS Conference (AIDS 2016), held in Durban, South Africa. The study followed straight and gay couples in which one person has HIV and the other partner doesn’t. It found no HIV transmissions between couples in which the person with HIV had an undetectable viral load. Our story about the study was headlined “Published Interim PARTNER Findings Stress Power of HIV Meds to Prevent Transmission.” I agree that we could have been more specific. Perhaps something like, “Study Finds Zero HIV Infections From Undetectable Partners.” How does that grab you?
Thanks for being so open to feedback. Absolutely, that revised headline works. It highlights the significance of the findings. Going one step further, the study is specifically about the risk of condomless sex, so it may be more effective to say, “Study Finds Zero HIV Infections From Condomless Sex With Undetectable Partners.”
I think you can highlight what really matters about this study to people with HIV, their partners and their providers. For example, the article mentions the new analysis focused on 888 mixed-HIV-status couples, and a few paragraphs later it says that there were 22,000 incidents of condomless sex among the gay couples and 36,000 among the straight ones. Combining those numbers in some parts of the article would make it clearer that there were 58,000 condomless sex acts. That’s a significant number and may otherwise get overlooked if reporting the acts separately. And it’s important to emphasize the role of condomless sex in the study.
It’s a profound mental, cultural and social shift to acknowledge that people with HIV who are undetectable can have condomless sex with HIV-negative people without transmitting the virus.
I see your point on most of that. But in fact, in the PARTNER study, the accompanying editorial and press release include quotes such as, “Clinicians need to be clear that even though the overall risk for HIV transmission may be small, the risk is not zero and the actual number is not known, especially for higher-risk groups such as MSM [men who have sex with men].” 
The editorial from the press release, which is not officially the study, is the least supported and most cautionary piece of information that accompanied the study.

Why do you think it takes that tone? 
It’s no surprise that a study such as PARTNER that indicates that there is effectively zero or negligible risk from condomless sex between mixed-status couples will be met with significant pressure and pushback due to political, cultural and public health concerns. This will impact where and how soon it gets published, as well as how it is editorialized and reported. I work closely with Pietro Vernazza, MD, who is on the executive committee of PARTNER, the author of the Swiss Statement and on the board of PAC, who agreed to go on record about the issue:

The publication of this manuscript was delayed not by the author group but by an extremely hesitant editorial process with extremely long return times. It seemed to me that many editors and reviewers were hesitant to have this information published. This delay of the publication process might indicate that the reasons were not scientific, but political.

The cautionary words in the PARTNER press release and editorial such as “appears small,” “may be small” and “risk is not zero” greatly understate and minimize the significance of the study. Word choices like “negligible,” “effectively zero risk” or even “extremely small” would be more accurate and meaningful and have been used by other experts to describe this PARTNER’s result.

We could easily veer into a discussion over semantics and how people interpret specific words that convey risk—after all, there isn’t one agreed-upon measurement of risk—but I take it you believe the tone of the press release is intentionally cautionary? 
Even when they agree with the force of evidence from real-world and clinical trial experience, medical and public health professionals have been reluctant to communicate the significance and meaning of it because of two primary concerns:
  1. An increase in condomless sex among people with HIV who are undetectable will lead to an increase in STIs; and
  2. People with HIV might not understand that staying on treatment is essential to maintain an undetectable viral load. For instance, they might interrupt treatment by personal choice or due to circumstances outside of their control and unknowingly experience an increase in viral load and risk of HIV transmission.
Many AIDS service organizations and community-based groups and medical providers selectively choose to discuss the science with patients and clients whom they judge are “responsible” (for example: monogamous and with a stable linkage to treatment) rather than directly address the impacts of risk compensation and disinhibition through education and access.  

It’s my experience that researchers are loath to speak in absolutes. You won’t find them saying there is absolutely zero risk of getting HIV—even if no one contracts it in the study—because researchers think of outlying and perhaps unknown factors as well as long-term risk (longer than the period of the trial). How does this affect your ability to get your “undetectable = uninfectious” message out? 
We don’t expect researchers to say absolutely zero risk, but some of the undisputable world leaders on the topic have said “negligible risk,” “uninfectious,” “not infectious,” “not contagious” and “effectively zero risk.” We’re pleased with all of those terms!
The Undetectable = Uninfectious movement has been building for quite some time. You’ll be hearing more about it from the Prevention Access Campaign and on my POZ Blog.
It’s a profound mental, cultural and social shift to acknowledge that people with HIV who are undetectable can have condomless sex with HIV-negative people without transmitting the virus. Getting to that point means rewiring 35 years of deeply entrenched fears of HIV and the people who have HIV and challenging the longstanding unproven assumption that condoms are always necessary to prevent HIV transmission. And the stigma and assumptions influence policies and practices even within the HIV prevention field.
There’s also the fear of being the first. At this point, only the Terrence Higgins Trust in the United Kingdom has said “Undetectable = Uninfectious” or “negligible risk.” None of the major HIV and federal public health agencies in the United States are even close to saying it. There’s a much greater level of comfort to continue to be cautionary and risk-averse and indicate there’s a smaller risk, but there’s still a risk. So, in a sense, people with HIV are still a grenade, a smaller grenade, but still a grenade. And, therefore, the misinformation and HIV stigma continue!

Bruce Richman cofounded the Prevention Access Campaign.
There was major progress in the United States last week: The pioneering Demetre Daskalakis, MD, MPH, assistant commissioner at the Bureau of HIV/AIDS Prevention and Control at New York City’s health department, became the first public official in the country to officially endorse “negligible risk” when he endorsed PAC’s Undetectable Primer/Consensus Statement along with other globally recognized experts on this topic from the United States, Australia, Switzerland and Denmark (including Myron Cohen, MD; Andrew Grulich, PhD; Jens Lundgren, MD, DMSc; and the aforementioned Vermazza). Many of PAC’s community partners will be shifting to similar messaging in the coming months.
Why is the PARTNER study so important to your messaging? Other studies such as the HPTN 052 study have also proved that treatment is prevention.
PARTNER is the largest study to include extensive data on both vaginal and anal sex without condoms. It also included anal sex among the heterosexual couples, not just the MSMs. Another critical finding in PARTNER is that having a sexually transmitted infection (STI) or likely viral blip did not affect risk, which is also a finding of the Canadian consensus statement in the context of criminal law—signed by more than 70 HIV specialists and the largest infectious disease association in Canada.

Our discussion brings up the differing roles of researchers, reporters and activists. Speaking for myself, I’m not comfortable telling a reader, “Hey, these results mean you have no risk and should harbor zero fears of HIV being transmitted from an undetectable person.” But I am comfortable including that perspective from a respectable source or trying to put the level of risk in a context the readers can better understand. 
I feel the same way. Neither of us is in the position to make a judgment about another person’s comfort and level of acceptable risk. Prevention Access Campaign points to and aggregates the studies and builds consensus among the top researchers so people can make informed decisions as to what makes sense for them. And we can help point out certain studies, decisions or opinions that may not be driven by science but by other factors. A large part of our role is to investigate and break through the politics, stigma and phobias that interfere with free flow of information.
While this isn’t in the study, it’s important to point out a few things:
  • Depending on the drugs employed it may take as long as six months for the viral load to become undetectable.
  • Staying undetectable requires excellent adherence to treatment.
  • Having an undetectable viral load prevents only HIV, not other STIs or pregnancy. Condoms protect against HIV as well as other STIs and pregnancy.
  • Many people with HIV may not be in a position to reach undetectable because of various challenges related to access to treatment (for example, poor health care systems, poverty, denial, stigma, discrimination, criminalization) or antiretroviral toxicities, or they may not be ready or willing to start treatment. There are many barriers to testing, treatment and long-term adherence outside the control of people living with and vulnerable to HIV that must be addressed.
Finally, PARTNER is part of a substantial and growing body of real-world and clinical evidence that is proving that while HIV is not always transmitted even with a detectable viral load, when a person living with HIV is on meds and has an undetectable viral load, this both protects his or her own health and prevents new HIV infections.
For more about PAC, visit PreventionAccess.org, where you can also learn about its Undetectable = Uninfectious campaign. And you can read Bruce Richman’s inaugural POZ Blog here.



THE END OF AIDS?  PBS special report on HIV/AIDS


Scientists have isolated potent HIV antibodies — immune system fighter proteins targeted specifically against the virus — that have implications for the prevention and even destruction of the virus that causes AIDS.

The powerful, broadly neutralizing antibodies are produced by an extremely small, “elite” group of HIV-positive individuals. The antibodies have kept them alive and in some cases thriving for many years without the use of antiretroviral drugs.

Scientists have harnessed these super antibodies, which recognize and disarm many different strains of HIV, and have mass-produced them with the aim of giving them to normal HIV patients.

Using the latest technology to cull and replicate the most potent antibodies, researchers tested the neutralizing proteins in a group of 13 individuals. All of the participants had been on antiretroviral drugs for a long time.

Antiretrovirals suppress HIV, but don't kill certain cells that act as reservoirs and harbor the virus. That means the virus can roar back to life when the drugs are stopped, in a process called viral rebound.

Writing in the journal Nature, the researchers said that among people who did not receive the new antibody, called 3BNC117, viral rebound occurred in about two and a half weeks. Those who did receive it were able to delay rebound by as long as almost 10 weeks in some cases.

'Kick and kill'

Michel Nussenzweig of Rockefeller University in New York, a corresponding author of the study, said 3BNC117 might one day be able to destroy the virus that causes AIDS.

“People have thought for a long time that one way to think about a cure strategy would be to do something called 'kick and kill' — that is, to activate the viruses that are in the latent reservoir and then use an agent like an antibody, for example, that would be able to see the activated cells that are starting to produce the virus and kill them,” Nussenzweig said.

Nussenzweig and colleagues are planning experiments using a cancer drug that unmasks the virus hidden in reservoir cells, and then killing them with 3BNC117.

One of the benefits of the antibody is that it doesn’t seem to have any side effects, according to Nussenzweig.

“They were made originally by human beings and we have not modified them at all," he said. "So they are completely natural products and should not have major side effects. In fact, the people who received them so far — and it’s a small number — have not reported any significant problems.”

Nussenzweig said a large clinical trial in Africa, using a similar neutralizing antibody developed by the vaccine center at the National Institutes of Health, is underway to see whether injections of the protein can protect women at risk of infection.

voanews.com by
(Jessica Berman)
                                 Intravaginal Ring Loaded with Tenefovir

An intravaginal ring loaded with tenofovir disoproxil fumarate (TDF, Viread) provided mucosal tenofovir concentrations high enough to protect against ex vivo HIV challenge in a 14-day placebo-controlled trial that enrolled healthy women. Product-related adverse events were all grade 1.

TDF with or without emtricitabine has proved effective as oral pre-exposure prophylaxis (PrEP) in women and men. The high tissue and cell penetration of TDF and its long intracellular half-life make it a good candidate for intravaginal ring administration, which could promote better adherence than daily or as-needed oral or gel TDF. Also, TDF retains anti-HIV activity in the presence of seminal plasma. A TDF intravaginal ring completely protected macaques from 16 weeks of intravaginal simian SIV challenge.

U.S. academic researchers recruited 30 healthy, sexually abstinent women 18 to 45 years old and randomized them after cessation of menses in a 1:1 ratio to insert a polyurethane reservoir intravaginal ring bearing TDF or to insert a placebo ring. Participants gave blood and vaginal swab samples on study days one, three, seven and 14, and they removed rings on day 14. They provided additional samples two to four and seven days after ring removal. Researchers also collected an ectocervical biopsy on day 14 for pharmacokinetic analysis and rectal swabs on days seven and 14.

Age averaged about 29 years in study participants and body mass index about 25 kg/m2. One woman withdrew from the study. Rings remained in place for 14 days in all other women, all of whom reported it was very easy or somewhat easy to wear.

Researchers recorded 29 adverse events in 12 women randomized to the TDF ring and 14 adverse events in seven women randomized to placebo. Eight events judged to be product related occurred in six women randomized to TDF and in one randomized to placebo. All product-related events involved cervical or vaginal discharge and were grade 1. There were two nonproduct-related grade 2 adverse events and no grade 3 or 4 or serious adverse events.

The TDF ring provided high tenofovir disoproxil (TFV-DP) and tenofovir concentrations in cervicovaginal fluid (CVF) from the vagina, ectocervix and introitus within one day of insertion, and concentrations remained high through day 14. After ring removal, median initial tenofovir half-life in CVF from the vagina, ectocervix and introitus stood respectively at 14, 12 and 11 hours. Median tenofovir concentrations remained above 1000 ng/mL two to four days after ring removal, a finding suggesting that the ring could protect women who remove the device before sex.

Median tenofovir and TFV-DP concentrations in ectocervical biopsies collected on day 14 were respectively 5.4 ng/mg and 120 fmol/mg. Rectal tenofovir could be measured in five of five participants who agreed to anoscopy on day seven and in four of five on day 14. Median CVF vaginal-to-rectal fluid ratio was 104 on day seven and 240 on day 14.
An ex vivo model using T cells challenged with HIV-1 in the presence of CVF collected from the cervix indicated 29% median inhibitory activity at enrollment, 96% inhibitory activity on day seven and 94% inhibitory activity on day 14.

The researchers conclude that the TDF ring "is safe, well tolerated, and results in mucosal tenofovir concentrations that exceed those associated with HIV protection." On the basis of their results, the authors “anticipate that the ring will continue to deliver ~5-6 mg/day of TDF for 30-45 days and will result in very rapid steady state tissue TFV-DP concentrations that exceed those achieved following oral TDF PrEP in adherent women, but with significantly lower systemic concentrations, thus avoiding potential toxicities."

Mark Mascolini writes about HIV infection. 

This month in HIV Research: When New Meets Old
By Myles Helfand
From TheBodyPRO.com

This week, we got our first published glimpse of how the new tenofovir stacks up against the old tenofovir after two full years of first-line therapy. We were also given a first look at what a long-acting form of pre-exposure prophylaxis (PrEP) might do for rates of HIV infection and mortality among high-risk populations -- and what it might cost. Plus, we were given a critical new resource to help improve HIV testing and outreach among trans people. To beat HIV, you have to follow the science!
First-Line Therapy Comparison: TAF vs. TDF at Week 96

At 96 weeks, tenofovir alafenamide (TAF) continues to keep pace virologically with tenofovir disoproxil fumarate (TDF, Viread) in treatment-naive people with HIV, while exhibiting a superior toxicity profile, according to study results published in the May 1 issue of the Journal of Acquired Immune Deficiency Syndromes.
The study summarizes the findings of two Phase 3, double-blind, placebo-controlled trials that randomized 1,733 antiretroviral-naive volunteers to receive elvitegravir/cobicistat/emtricitabine coformulated with either TAF or TDF. After two years on the study drugs, there was no significant difference between the percentage of people with a viral load below 50 copies/mL who received TAF (86.6%) and those who received TDF (85.2%), with virtually no emergence of resistance among those whose therapy failed in either arm. However, marked differences were noted between the two drugs on the toxicity front.

"With TAF, there are smaller declines in bone mineral density and more favorable changes in proteinuria, albuminuria, and tubular proteinuria, and no cases of proximal tubulopathy compared with 2 for TDF," the study authors noted. In fact, differences in bone mineral density widened between weeks 48 and 96 despite increased usage of drugs to improve bone density among TDF recipients, they stated. The authors also commented on a continuation of more favorable renal markers among TAF recipients relative to TDF recipients in the span between week 48 and week 96.
"Together, these longer-term safety data support the hypothesis that circulating levels of TFV [tenofovir] are responsible for the bone and renal toxicity of TDF and that the markedly reduced TFV level delivered by TAF minimizes such exposure and is protective against renal and bone effects," the researchers conclude.
Potential Value of Long-Acting PrEP for South African Women at High HIV Risk

The eventual use of long-acting antiretrovirals for PrEP will probably prevent more HIV infections among high-risk South African women than the current PrEP standard regimen, but at greater financial cost, according to the results of an extensive computer simulation by researchers in the U.S. and South Africa.
Appearing in the Journal of Infectious Diseases, the study, led by Rochelle Walensky, M.D., M.P.H., of Massachusetts General Hospital, calculated the comparative cost and effectiveness of three PrEP strategies implemented among a simulated cohort of young South African women (mean age 18). Using an extensive array of existing study data to inform their models, the researchers sought to generate reasonable estimates of the impact of no PrEP, standard PrEP (using existing oral formulations) and long-acting injectable PrEP on lifetime HIV risk and five-year mortality, as well as the cost-effectiveness of each approach.
The simulation found that, after an average of eight years of PrEP use, reasonably effective (75%) long-acting PrEP reduced lifetime HIV incidence among the virtual cohort by 19% compared to no PrEP (510 cases per 1,000 high-risk women, compared to 630); by comparison, reasonably effective (62%) standard PrEP reduced lifetime HIV incidence by 14% over eight years compared to no PrEP (540 cases per 1,000 high-risk women). Within five years, long-acting PrEP would avert 156 new HIV infections and 16 deaths, while standard PrEP would avert 127 new HIV infections and 15 deaths, the model predicted.
Although both PrEP approaches were deemed to be cost-saving relative to the use of no PrEP at all, standard PrEP was found to be the least expensive over the course of a cohort member's lifetime, at US$5,270 total (compared to the slightly higher $5,300 for long-acting PrEP, and the sharply higher $5,730 for no PrEP, which included the costs of HIV care and antiretroviral therapy for the greater number of women who would become infected). Long-acting PrEP program implementation was found to have a much higher ramp-up cost than standard PrEP implementation, but a lower cost afterward.
"The delivery of existing oral PrEP formulations, which are very cost-effective, should be expanded and optimized for young, high-risk South African women," the researchers concluded. In addition, they urge that "the research and development effort should be expanded to bring a viable [long-acting] PrEP formulation to market."
UCSF Releases Transgender HIV Testing Toolkit

TheBody.com and TheBodyPRO.com.
Follow Myles on Twitter: @MylesatTheBody.

PrEp KNOw About it!!!!!!!!!!! 
Know How for whom why
This article is for people who may be at risk for an HIV infection because they have unprotected sex or would like to change their present form of protection. The goal is to help you understand PrEP, a medication that can help you prevent HIV.
This article will cover:
  • What is PrEP?
  • I have an STD. Why all the questions from my doctor?
  • Why would I take PrEP if I don't have HIV?
  • Does my sex life put me at risk for HIV?
  • Do I have other risk factors for HIV?
  • Do I have to use condoms if I take PrEP?
  • Will PrEP keep me from getting other STDs?
  • What can I do if I think I need PrEP?
  • Find the article at http://education.webmd.com
  • Breaking in Aug.
    The US Food and Drug Administration (FDA) has approved the first-ever diagnostic test that differentiates between types of HIV infection.
    The Bio-Rad BioPlex 2200 HIV Ag-Ab assay (Bio-Rad Laboratories, Inc, Hercules, California) distinguishes between HIV-1 antibodies, HIV-2 antibodies, and HIV-1 p24 antigen in human serum or plasma specimens. It is intended for use with the BioPlex 2200 System, which was cleared by the FDA in 2004.
    HIV-1 is the most commonly found type around the world. HIV-2 is found primarily in West Africa but has also been identified in the United States. The two viruses are similar, but distinct. Differentiating between the types is important for patient care because they progress at different rates, said Karen Midthun, MD, director of the FDA's Center for Biologics Evaluation and Research, in a news release.
    The new assay allows results of antigen and antibody detection to be reported separately. Because HIV antigens and antibodies appear and are detectable at different stages of the infection, reporting of the distinct results helps differentiate between acute and established HIV infection, according to the FDA.
    The Bio-Rad BioPlex 2200 HIV Ag-Ab assay can be used in adults, children aged 2 years or older, and pregnant women. It may also be used to screen organ donors for HIV-1/2 when the blood specimen is collected while the donor's heart is still beating. However, the assay is not approved for use in screening blood or plasma donors, except in urgent situations where traditional, licensed blood-donor screening methods can't be used.

July 2015

If Not a Cure then Permanent Remission

Best known as the co-discoverer of HIV, French scientist Françoise Barré-Sinoussi, MD, PhD, told CNN that a cure for HIV “is almost an impossible mission.”

Why? “Because the reservoir of cells is not only in the blood,” the Nobel Prize winner explained. “How to eliminate all the cells which are reservoirs is why I say it’s an impossible mission. They are everywhere—in the gut, in the brain, in all the lymphoid tissue. 

“Even if you have a very efficient strategy,” she continued, “how you can make sure that there’s not one or two cells still there and if one is there the virus will reappear again? That’s why I say it’s an impossible mission. But you never know.”

She was speaking about a sterilizing cure, which is when the virus is completely eradicated. This compares with a functional cure, in which the virus is under control without meds. 

When asked about a functional cure, Barré-Sinoussi said, “I prefer to say remission (when the virus is brought down to low levels in the body) … That’s possible. I’m convinced one day—I don’t know when—we will have a strategy to induce durable remission. I don’t believe that we will have only one treatment. It will be a combination of treatments. (But) we need both—a cure and a vaccine.”

Barré-Sinoussi spoke with CNN during the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Vancouver, British Columbia. She is a former president of the IAS, and she is also retiring next month because “in my country it’s mandatory to retire.” 

Fact-Checking AIDS Healthcare Foundation's Latest Anti-PrEP Screed
by Benjamin Ryan

Just in time for gay pride, AIDS Healthcare Foundation published an adcriticizing pre-exposure prophylaxis (PrEP) in various gay publications around the country. The ad, ironically entitled “The War Against Prevention,” is nothing short of a scurrilous attack on Truvada (tenofovir/emtricitabine) as HIV prevention and on gay men’s right to protect themselves against HIV. The missive uses crafty manipulations, and select omissions, of the science behind PrEP to push the agenda of AHF’s notoriously anti-PrEP president, Michael Weinstein.
  eview was conducted under the assumption that, because AHF placed the ads only in gay publications, this particular missive only addresses the concerns of gay men.

Something of a lone, and ferocious, wolf in the public opposition to PrEP, Weinstein has tinkered with his stance over time as increasing scientific evidence has supported Truvada’s use as a tool to fight the spread of HIV. Currently, he claims not to be against PrEP, saying that he maintains a “nuanced” position by arguing that Truvada may be a worthy option for some individuals, but should not be used as a broad public health intervention. 

“Mass PrEP administration is a dangerous experiment that is not supported by medical science and is currently resisted by doctors and patients alike,” he claims in the ad.

Instead, he believes that the best way to prevent HIV transmission is through behavior modification and condoms, as well as through testing for the virus and treating people with HIV in order to render them vastly less infectious. This is a standpoint that dovetails neatly with his position as the leader of the world’s largest provider of treatment for the virus, with more than 420,000 patients in 36 countries.

Fact check:
  • Claim: Behavior modification, while never 100 percent effective, has been a remarkable success with gay men.
    • This is definitely true when you look at the entire history of the U.S. HIV epidemic. In the 1980s, the use of condoms and other forms of behavior modification among American gay men were highly successful in reducing what was initially a soaring rate of HIV infection in that population. However, in recent years, as memories of the horrors of the early AIDS crisis have faded and a new generation rises that never knew those days, gay men have increasingly shifted their sexual behavior in the opposite direction. Condom use has decreased among the population while the HIV infection rate has risen once again.
  • Claim: The ad implies that those supporting PrEP advocate giving up on condoms.
    • The Centers for Disease Control and Prevention (CDC), which recently has become a strong advocate for PrEP, encouragesusing condoms with Truvada. However, there are certainly PrEP advocates who have quite publicly celebrated Truvada as a tool by which to enjoy condomless intercourse.
  • Claim: Truvada has not caught on with medical providers or patients.
    • Weinstein relies on Gilead Sciences’ report that only 5,272 PrEP prescriptions were written through 2014. There are many limitations to that estimate that make it a highly unreliable barometer for PrEP use in the United States. It is based on approximately 39 percent of U.S. retail pharmacies and less than 20 percent of Medicaid data, and does not include the many gay men receiving PrEP through a study. 
    • Research suggests that approximately 4,000 San Franciscans are taking PrEP. In New York State, PrEP prescriptions filed through Medicaid rose 272 percent between June 2014 and February 2015, from 305 to 832. A recent POZ survey found that various medical providers across the country have seen dramatic increases in prescription rates over the past two years. About 400 people currently receive PrEP form the Callen-Lorde Community Health Center in New York City.
  • Claim: 95 percent of HIV medical providers are “concerned that their patients would not adhere” to the daily Truvada regimen.
    • This refers to a survey of members of American Academy of HIV Medicine, which the AAHIVM published in April. Indeed, 95 percent of the 324 respondents said that “concerns about adherence” to Truvada were “very important” when deciding whether to prescribe PrEP. However, as physicians have argued since Weinstein began publicizing this figure, it is only natural that a clinician should be concerned that patients will not adhere to any drug. This figure, therefore, does not necessarily imply grave reservations about PrEP in particular.
    • In the same survey, 79 percent of the clinicians said they were “very likely” to prescribe PrEP to MSM having sex with an HIV-positive partner, while 66 percent said they were very likely to prescribe to MSM at risk for contracting HIV.
  • Claim: Every published study of PrEP has shown major efficacy problems. For example, the largest study among MSM (iPrEx) had “only a 42 percent efficacy.”
    • By limiting this claim only to published research on PrEP, Weinstein leaves out the results of both the PROUD and IPERGAY studies, which each showed an effectiveness rate of 86 percent among MSM. (Effectiveness, which refers to a drug’s actual, across-the-board success, is the correct term; efficacy only refers to a drug’s potential for success.) PROUD studied PrEP among very high-risk MSM in the United Kingdom and was designed to reflect real-world use of Truvada. IPERGAY tested an intercourse-based dosing protocol of PrEP in which MSM participants in France and Canada were instructed to take Truvada only in the days surrounding a potential HIV exposure.
    • The iPrEX study and its open-label extension (OLE) phase, the two published studies of PrEP among MSM, had respective effectiveness rates of 44 percent (not 42 percent) and 50 percent. Weinstein has long characterized these rates as failures. On the contrary, these figures can and should be viewed as successes: The trials succeeded at lowering the rate of HIV by a considerable amount among the high-risk participants taking Truvada. A true failure would have been if PrEP increased or led to no change in HIV rates, or perhaps if the risk reduction was too small to justify a PrEP roll-out. Weinstein also omits the fact that the U.S. participants of the OLE trial adhered at a much higher rate than their international counterparts, suggesting that they enjoyed a greater benefit from PrEP than the study group as a whole.
  • Claim: “In the most successful of all the published studies [on PrEP] more than half of the patients did not take the medication as directed.”
    • According to AHF spokesperson Christopher Johnson, this claim refers to the Partners PrEP trial, which studied PrEP among heterosexual couples in Kenya and Uganda and had a 67 percent success rate. Since the study did not include MSM, its results are not particularly relevant to a gay male audience.
    • Johnson backed up AHF’s claim about the lack of adherence in Partners PrEP with the fact that an estimated 55 percent of the study’s participants had at least one gap of 72 consecutive hours of nonadherence. However, the same analysis showed that just 23 percent of the participants had at least one weeklong adherence gap. According to the head of Partners PrEP, Jared Baeten, MD, PhD, a professor at the University of Washington School of Public Health, Weinstein’s assertion that the study’s participants were highly nonadherent is a “very skewed” interpretation of the research. More than 80 percent of the participants, Baeten points out, had detectable study drug in their blood and 70 percent had concentrations consistent with daily use. Additionally, Baeten states that the Partners PrEP substudy that looked at the adherence gaps measured daily pill-taking through the use of an electronic pill bottle, and that 72-hour gaps may reflect people not taking PrEP while risk was low (perhaps while not having sex) or taking out multiple doses for use while traveling.
  • Claim: Those in the Partners PrEP study who were most at risk were also the least likely to adhere properly.
    • AHF’s Christopher Johnson refused to provide a citation for this claim. University of Washington’s Jared Baeten asserts the claim is false. He and his colleagues have conducted a number of analyses to determine what factors affected adherence in Partners PrEP (a study which, again, did not include MSM), and found that a consistent factor linked with lower adherence was not having sex. This suggests that, in fact, being low risk was linked to low adherence, and, conversely, that higher risk people adhered at higher rates.
    • In iPrEx OLE, the higher-risk participants were more likely to opt to start PrEP in the first place (those who chose not to take Truvada served as a control group), and were then more likely to adhere.
  • Claim: Not-yet-published European research on intermittent (also known as intercourse-based) PrEP use among MSM has shown very high rates of sexually transmitted infections (STIs) and poor adherence.
    • The IPERGAY study indeed showed a very high rate of STIs among the MSM participants—35 percent of the participants contracted one during the study—which is indicative of the fact that they were at high risk for HIV, and therefore good candidates for PrEP. There was no evidence that men increased their sexual risk taking during the study, so PrEP itself cannot be blamed for those STIs. 
    • With an 86 percent effectiveness rate, the dosing strategy in IPERGAY was actually a great success, indicating that adherence was quite good. It is not clear whether the specifics of the protocol itself led to such a high risk reduction or just the fact that the men wound up taking PrEP often enough to enjoy a significant risk reduction regardless of the exact timing of the pill taking. (The iPrEX OLE results suggest that taking Truvada four times a week offers maximum protection against HIV.) The two participants given Truvada who did contract HIV had apparently stopped taking PrEP several weeks before becoming infected.
  • Claim: Concerns about the effectiveness of PrEP in the clinical trials would be “nonexistent if the patients wore condoms.”
    • PrEP is most strongly urged for MSM who are already not using condoms. In a perfect world, all those men would use latex for every potential exposure to the virus. PrEP acknowledges the reality that these men may not be willing or able to change their behavior, but that they may indeed have the capacity to follow a drug regimen that will lower their risk.
    • PrEP’s HIV risk reduction benefits can complement those of condoms; the two prevention techniques are not mutually exclusive, and indeed are often used together.
  • Claim: According to the CDC, three out of four MSM used condoms during their last sexual encounter.
    • True, but highly misleading. The same 2011 CDC report states that, out of 8,000 MSM in 20 U.S. cities, 57 percent reported having anal sex without a condom during the previous year.
  • Claim: “The entire body of scientific data demonstrates that Truvada will not be successful as a mass public health intervention.”
    • The PROUD study strongly suggests otherwise: It examined PrEP’s use among high-risk MSM in a real-world setting and had an 86 percent success rate.
  • Claim: Weinstein insinuates that “the condom culture that has been so hard fought since the [beginning] of AIDS” will disappear.
    • This is a worthwhile concern to raise. At this time, none of the studies of PrEP among MSM support the notion that Truvada will lead to a reduction in condom use among that population. However, anecdotal evidence suggests otherwise: that PrEP may indeed contribute an already dropping rate of condom use among MSM. It is possible that one of the reasons that men in the PrEP studies don’t use condoms less while on Truvada is that they already weren’t using them much to begin with; being at high risk for HIV is a qualification for entry into the studies.
  • Claim: The condom is the most effective prevention method for an individual who has multiple partners or whose partner has multiple partners.
    • If an individual gay man takes PrEP daily, Truvada's 99 percent or greater effectiveness likely offers superior protection against HIV than regular condom use. (And of course he may use condoms in addition to Truvada.) It’s very hard to pin down exactly how effective condoms are when used for anal sex; research is scant, and a recent CDC paper claiming condoms are only 70 percent effective when used consistently and correctly by MSM is based on highly questionable reasoning. But in a nutshell, it’s simpler to use Truvada correctly—you swallow a daily pill—than condoms. Condoms may fail due to putting them on wrong, improper lubrication, or not keeping them on for the entire act of intercourse, a common practice. Psychologists have also argued that it is easier to adhere to a drug that is taken as a part of a daily routine than it is to use a condom during moments when that sense of personal responsibility may be challenged by sexually and emotionally charged experiences.
    • Weinstein’s argument here seems to contradict his claim in the previous paragraph that “Truvada can absolutely be the right decision for specific patients.” 
  • Claim: If everyone with HIV in the United States knew their status, went on treatment and had an undetectable viral load, there would be no new HIV infections.
    • This sweeping claim is categorically false because of the impossibility of alerting everyone to their HIV status the instant they contract the virus. During the first few months of infection, viral loads tend to be very high, making an individual highly infectious. Additionally, acutely infected individuals may be engaging in the same high-risk behaviors that led them to contract the virus in the first place, allowing them to transmit the virus to others before they are tested. Estimates vary, but scientists believe a considerable proportion of new HIV cases transmit from people recently infected with the virus.
    • Furthermore, as Weinstein points out in the ad, just 30 percent of Americans living with HIV currently have an undetectable viral load. So his vision of treating our way to zero HIV transmissions is a long way off, to say the least. In the meantime, the scale-up of PrEP among high-risk populations will hopefully help reduce infection rates, in particular among MSM.

 April 2015


Inflammation and gut leakage remains elevated in people with HIV despite early antiretroviral treatment

Inflammatory changes and damage to the gut begin very soon after initial HIV infection, and may not return to normal even when people start antiretroviral therapy (ART) very early, researchers reported at the Conference on Retroviruses and Opportunistic Infections (CROI 2015) last month in Seattle, USA. Biomarkers of inflammation, coagulation and fibrosis increased early on, and while they generally decreased after starting ART, they did not fall to levels seen in HIV-negative people.
Netanya Sandler Utay of the University of Texas Medical Branch, Jintanat Ananworanich of the US Military HIV Research Program and colleagues aimed to determine whether ART started during acute HIV infection would normalise biomarkers of gut damage, inflammation and coagulation that predict morbidity and mortality during chronic HIV infection.
This analysis included 78 participants in the ongoing SEARCH (RV254) study who were diagnosed during acute HIV infection and started ART within 0 to 5 days. The cohort is made up of people who sought HIV testing in Bangkok, Thailand, most of whom are men who have sex with men. More than 90% were male and the median age was 28 years. There was also a control group of 109 people without HIV infection; this group was matched for age but included more women (23%). 
Among the HIV-positive participants, the median CD4 cell count at study entry was 384 cells/mm3(range 293-525) and the median HIV viral load was 5.6 log10 copies/ml. Using Ananworanich's 4th generation staging system, 20 people were diagnosed during stage 1 of infection (HIV RNA positive; median 12 days after HIV acquisition), 15 during stage 2 (p24 antigen positive; median 16 days) and 43 during stage 3 (HIV antibody positive; median 18 days). About 40% started a standard ART regimen consisting of efavirenz (Sustiva) plus tenofovir/emtricitabine (the drugs in Truvada), while more than half started a more intensive regimen containing the same three drugs plus maraviroc (Celsentri/Selzentry) and raltegravir (Isentress).
The researchers assessed changes in biomarkers of microbial translocation (damage to the gut that allows leakage of intestinal bacteria), inflammation, coagulation (blood clotting) and fibrosis (accumulation of connective tissue). These processes are associated with complications and death among people with chronic HIV infection, but how soon they occur and how they might be affected by early treatment is not well understood. 
Specifically, Utay and her team measured plasma levels of the following biomarkers at the time of HIV diagnosis or study entry (week 0) and again at weeks 2, 12, 24, 36, 48 and 96:
  •   Intestinal fatty acid binding protein (I-FABP), a marker of turnover of enterocytes, a type of absorptive cell in the gut lining;
  •   Hyaluronic acid, a fibrosis marker;
  •   D-dimer, a coagulation marker;
  •   C-reactive protein (CRP), an inflammation marker;
  •   Soluble CD14 (sCD14), an immune cell receptor that recognises the bacterial toxin lipopolysaccharide (LPS) and is a marker for microbial translocation and monocyte activation;
  •   Interleukin 6 (IL-6), a pro-inflammatory cytokine;
  •   IL-6 receptor (IL-6R), a cytokine receptor that facilitates IL-6 signalling.
At week 0 all biomarker levels were significantly higher in HIV-positive participants – whether they were diagnosed at stage 1, 2 or 3 of acute infection – compared to the HIV-negative group, and they generally remained elevated through weeks 48 and 96. HIV-negative participants saw no changes in any of these biomarkers over the course of the study.
I-FABP – the marker of gut damage – increased significantly by week 2 in HIV-positive people at all stages of acute infection, and remained elevated after starting ART.
Hyaluronic acid levels were significantly elevated at all time points in the HIV-positive group. Levels tended to fluctuate – falling around week 2, rising around week 24, then falling again – but never fell to the level of the HIV-negative group.
D-dimer levels were significantly higher at weeks 0 and 2 in HIV-positive compared to HIV-negative people, but decreased by week 12 and reached levels similar to those of the uninfected group.
CRP levels in the HIV-positive group were elevated at week 0, then decreased from week 2 to week 12; however, levels remained significantly higher at all time points except week 48 compared to the HIV-negative group. sCD14 levels decreased by week 12, but nevertheless remained significantly elevated at all time points compared to the HIV-negative group.
IL-6 levels in HIV-positive people with all stages of acute infection showed a less consistent pattern, but generally decreased by week 24 or 48. Soluble IL-6R levels decreased significantly in the HIV-positive group by week 24 on ART.
"Biomarkers of enterocyte death, microbial translocation, inflammation, coagulation and fibrosis increase early in acute HIV infection," the researchers concluded. "I-FABP increases and remains elevated during infection despite suppressive ART, suggesting on-going enterocyte damage or turnover."
"[S]uppressive ART started during acute HIV infection does not eradicate the inflammation associated with increased morbidity and mortality in treated chronic HIV infection," they continued. However, they noted, most biomarkers decrease in people who start ART during acute infection to levels lower than those observed in patients who start ART during chronic HIV infection. 
March 2015

In order for viruses to reproduce, they must infect a cell. Viruses are not technically alive: they are sort of like a brain with no body. In order to make new viruses, they must hi-jack a cell, and use it to make new viruses. Just as your body is constantly making new skin cells, or new blood cells, each cell often makes new proteins in order to stay alive and to reproduce itself. Viruses hide their own DNA in the DNA of the cell, and then, when the cell tries to make new proteins, it accidentally makes new viruses as well. HIV mostly infects cells in the immune system.
Infection: Several different kinds of cells have proteins on their surface that are called CD4 receptors. HIV searches for cells that have CD4 surface receptors, because th 

End of HIV?
New Lab Fabricated Protein Kills of the Mutants of the HIV Virus


An HIV-positive freelance writer on being proud about your undetectable viral load. 
David Duran
David Duran
With the news spreading across the Web of the PARTNER study showing that no HIV-positive individual with an undetectable viral load has transmitted HIV within the first two years of the study, HIV-positive men are tossing out their condoms and celebrating. All online profiles are immediately being changed to say "negative," and the fear of ever having to disclose their status is now a thing of the past. Let that sink in for a moment. Now, how stupid does that sound? 

Well, you most likely won't be surprised by the reactions from the haters and skeptics to this monumental news. This news has been long-awaited by those who know their positive status, are taking medication and are taking care of themselves. Is it a license to be reckless? No, but it is a reassurance that treatment as prevention does work. 

As someone who happens to be HIV positive, my major fear regarding the disease is passing it on to someone else. My second fear is the rejection I could possibly face with disclosure. Do I disclose before being intimate? If a partner asks me upfront, I am always honest right back, and when the topic is left up to me to bring up, I'd say that I do initiate the conversation the majority of the time. But in the back of my head, I always would reassure myself that my viral load is undetectable and most likely would not be putting anyone at risk. With this landmark finding, is it possible that everyone, especially gay men, will be more inclined to get tested, know their status and be upfront and open about it all the time? 

In a perfect world, everyone would get tested, know their status, and take the appropriate steps thereafter. The shame and stigma that surround HIV would diminish, and the world would go on as normal, and HIV would be controlled and the spread of the virus contained. Having an undetectable viral load would be sexy. Knowing your status and getting tested regularly would be, well, regular. Being HIV positive and having an undetectable viral load would be considered the same thing as being HIV negative. Instead, we would frown upon those who don't know their status. Being HIV positive and having an undetectable viral load would be accepted, especially within the gay community. 

So will all this happen overnight? Will Grindr or other dating apps see an increase in gay men changing their status to say, "Undetectable as of..."? In this dream scenario, HIV-positive people who are on treatment and taking care of themselves by maintaining an undetectable viral load would feel more empowered to come out and show everyone their A-plus report card each time they have their labs done, wearing those test results with honor and being proud for being healthy. 

Unfortunately, unless those of us who are HIV positive become more open about our status and stop hiding behind the stigma, things most likely won't change overnight. We can all already hear the naysayers with the release of the first two years of this second study. And at the same time, we shouldn't automatically ditch the condoms or all our safe-sex practices. As we all know, there is a world of other communicable infections. 

What I hope will not happen is for HIV-positive people with undetectable viral loads to hide behind these results and live life as if they were HIV negative. Not being able to transmit the virus is the only thing the two types of individuals have in common. An undetectable viral load is not to be used as a justification for not disclosing your status before engaging in unprotected sex. Instead, these results should build up your confidence so that you can be more open about your HIV status and, if you are HIV positive, keep up on maintaining your undetectable viral load as well as being healthy. 

The more we open up and discuss what it means to be HIV positive with an undetectable viral load, the more society, especially those within our own community, will begin to understand, learn and accept. With advancements in antiretroviral therapies, attaining and maintaining an undetectable viral load is not difficult, especially if treatment is started immediately after learning of a positive HIV status. 

The more information is put out there for the world to know and learn from, the easier it will become for the ignorance and discrimination surrounding HIV to be eliminated. So all my HIV-positive brothers and sisters who are on treatment and have reached an undetectable viral load, take a moment to breathe a sigh of relief. If you are like me and our first major fears align, this news will certainly help lift that extra weight that we had pushing us down. Be proud of having an undetectable viral load!

 David Duran

David Duran is a freelance writer. He writes extensively about travel, business, entertainment, LGBT issues and HIV/AIDS. This article originally was published on The Huffington Post.

In Cuba an aggressive new HIV Strain(new because is a strain, not because there is a new HIV) but because the virus mutates as it duplicates. Anything that is made in great quantities for years it doesn’t always comes out the same way.
A new HIV strain in some patients in Cuba appears to be much more aggressive and can develop into AIDS within three years of infection. Researchers said the progression happens so fast that treatment with antiretroviral drugs may come too late.
Without treatment, HIV infection usually takes 5 to 10 years to turn into AIDS, according to Anne-Mieke Vandamme, a medical professor at Belgium's University of Leuvan. According to the study, published in the journal EBioMedicine, Vandamme was alerted to the new aggressive strain of HIV by Cuban health officials who wanted to find out what was happening.
"So this group of patients that progressed very fast, they were all recently infected," Vandamme explained to Voice of America. "And we know that because they had been HIV negative tested one or a maximum two years before."
None of the patients had received treatment for the virus, and all of the patients infected with the mutated strain of HIV developed AIDS within three years.
While fast progression of HIV to AIDS is usually the result of the patient's weak immune system rather than the particular subtype of HIV, what's happening in Cuba is different.
"Here we had a variant of HIV that we found only in the group that was progressing fast. Not in the other two groups. We focused in on this variant [and] tried to find out what was different. And we saw it was a recombinant of three different subtypes."
The new variant, named CRF19, is a combination of HIV subtypes A, D and G.
HIV normally infects cells by attaching itself to what is called a co-receptor, and the transition to AIDS usually occurs when the virus switches -- after many years -- from co-receptor CCR5 to co-receptor CXCR4. The new strain makes the switch much faster.
The variant has been observed in Africa, but in too few cases to be fully studied. Researchers said the strain is more widespread in Cuba.

While the aggressive form of HIV responds to most antiretroviral drugs, people may not realize they have AIDS until it's too late for treatment to do any good. Vandamme said it's vital for people having unprotected sex with multiple partners to be tested for HIV early and often. 


Trending: January 2015N       New HIV drug Trending with use only every few months                                                                                   
The new drug cabotegravir (in vials above) has been shown to protect monkeys from infection by an HIV-like virus, and a clinical trial testing cabotegravir's safety and acceptability has begun. Unlike other preventive treatments, it would require only one injection every three months.
Credit: Zach Veilleux / The Rockefeller University
A regime of anti-HIV drugs -- components of regimens to treat established HIV infection -- has the potential to protect against infection in the first place. But real life can interfere; the effectiveness of this prophylactic approach declines if the medications aren't taken as prescribed.


HIV researchers hope a new compound, known as cabotegravir, could make dosing easier for some because the drug would be administered by injection once every three months. A clinical trial testing long-acting cabotegravir's safety and acceptability has already begun at multiple U.S. sites including The Rockefeller University Hospital. Meanwhile two new studies, including one conducted by researchers at the Aaron Diamond AIDS Research Center (ADARC) and Rockefeller University, published today (January 15) in Science Translational Medicine, show that long-acting cabotegravir injections are highly protective in a monkey model of vaginal transmission of a virus similar to HIV.
"Clinical trial results have demonstrated that the effectiveness of preventive oral medications can range with results as high as 75 percent effective to as low as ineffective, and a lot of that variability appears to hinge on the patient's ability to take the pills as prescribed," says study researcher Martin Markowitz, a professor at Rockefeller University and ADARC. "Long acting cabotegravir has the potential to create an option that could improve adherence by making it possible to receive the drug by injection once every three months."
Developed by ViiV Healthcare and GlaxoSmithKline, and previously known as GSK744 LA, cabotegravir is an antiretroviral drug. Antiretrovirals interfere with HIV's ability to replicate itself using a host cell and they are used to treat an HIV infection or to prevent those at high risk from acquiring it in the first place.
Cabotegravir belongs to a group of antiretrovirals that target integrase, an enzyme the virus uses to integrate itself into the cell's genome. This compound is a relative of an already FDA-approved integrase inhibitor, dolutegravir, but with chemical properties that allow it to be formulated into a long-acting suspension for injection.
A previous study by the ADARC and Rockefeller team in collaboration with ViiV Healthcare and GSK found long-acting cabotegravir could protect male rhesus macaque monkeys from exposure to a virus related to HIV. Following up on these results, a phase 2 clinical trial is now underway in a group of 120 men at low risk of infection. Before cabotegravir's effectiveness in high risk individuals can be tested, trials must show that study participants tolerate the drug well and find the quarterly injections, which are a novel approach to HIV prevention, acceptable.
Both new animal studies were conducted with women in mind; in 2013 women accounted for 47 percent of new HIV infections worldwide according to the Joint United Nations Programme on HIV and AIDS. Working separately, two teams tested the drug's ability to block vaginal transmission in two species of monkeys with different breeding cycles and susceptibility to infection.
First author Chasity Andrews, a postdoctoral fellow at ADARC and Rockefeller, and colleagues at ADARC, the Tulane Regional Primate Center and ViiV/GSK, studied female rhesus macaques treated with progesterone to increase their susceptibility to the virus. They found injections of long acting cabotegravir were 90 percent effective at protecting the monkeys from repeated high-dose exposures to the virus.
Meanwhile, the complementary study conducted by researchers at the CDC and ViiV/GSK found female pigtail macaques injected with cabotegravir were completely protected against multiple exposures to the virus.
"While we are still a long way off from showing that this drug works for HIV prevention in humans, our hope is that it may one day offer high risk women, as well as men, an additional option for HIV prevention," Markowitz says. "One of the lessons we have learned from contraception is the more options available, the better. We are hoping for the same in HIV prevention -- more options and better results."

Story Source:
The above story is based on materials provided by Rockefeller UniversityNote: Materials may be edited for content and length. 

January 15, 2015
NY State Task Force Finishes Plan to End AIDS by 2020

Last year, New York Governor Andrew Cuomo asked that a group be created to draw up a blueprint to end AIDS in the Empire State by 2020. This week, the Ending the Epidemic Task Force completed its plan, according to a Housing Works press release.

Charles King, the CEO of Housing Works, co-chaired the state task force along with Guthrie Birkhead, MD, MPH, a deputy commissioner with the state health department. The group is made up of more than 70 activists, researchers and health service providers.

The task force created “a visionary package,” said King in the release. “Ending New York’s epidemic means reducing new HIV infections from over 3,000 last year to under 750 in 2020 and ending HIV-related deaths. Reaching these goals will require dramatic scale-up of high-quality combination HIV prevention, including pre-exposure prophylaxis (PrEP), universal health coverage and primary care, scaled-up HIV testing, and full uptake of HIV treatment, to enable at least 85 percent of HIV-positive New Yorkers to achieve and sustain optimal health through an undetectable viral load.”

“The governor has allowed the task force to work in freedom,” said Mark Harrington, executive director of Treatment Action Group and the co-chair of the task force’s Data Committee. “We were never muzzled or told not to include something. The governor has already taken steps we were planning on recommending, such as requiring Medicaid and private insurance coverage for transgender health care.

Harrington added: “Now it will be up to the state legislature and local leaders to provide the support and necessary resources to achieve the vision laid out by Governor Cuomo and the task force.”

For more about the task force, click here.

Adam Gonzalez (publisher) writes on how the virus can be transmitted by a person who just tested negative.Also he reviews of how Prep can be used to keep the user negative without condoms and how a discordant couple can stay the way they are without one transmitting tot the other:

HIV Cases are Down so, How is HIV being Transmitted?

FY 2015 Budget Includes a $300M Increase for PEPFAR

In approving the fiscal year 2015 budget, the U.S. Congress secured a $300 million increase for the President’s Emergency Plan for AIDS Relief (PEPFAR), reports the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF).

PEPFAR is a U.S. global initiative to combat the HIV/AIDS epidemic around the world by working with the government and civil society leadership in various countries. In total, Congress approved $4.32 billion for PEPFAR in 2015, and it is funding the Global Fund to Fight AIDS, Tuberculosis and Malaria at requested levels.

According to EGPAF, PEPFAR directly or indirectly supports 7.7 million people on HIV treatment worldwide.

Researchers See New Avenue For HIV Cure: Endogenization

French scientists believe they have identified the means by which two HIV-positive men have been “spontaneously cured,” and that this insight may carve a new cure pathway, Yahoo News reports. Publishing their findings in Clinical Microbiology, researchers identified two HIV-positive men who are “elite controllers”—meaning their bodies control the virus without the aid of antiretrovirals—and theorize that enzymes have altered the virus’ genome in order to bring it to heel.

One of the men is a 57-year-old diagnosed with HIV in 1985. The other is 23 years old and was diagnosed in 2011. Neither has ever experienced any HIV-related disease, neither has detectable HIV in standard tests, and both have normal CD4 cell levels. The researchers drew viral DNA sequences that had been integrated into the men’s own genomes in order to perform tests and theorize how the men are able to control the virus.

The researchers propose that a common enzyme known as APOBEC altered the genetic code of HIV in each man’s body, rendering the virus unable to replicate, in a process known as endogenization. Though the men remain infected with HIV, researchers believe they can be categorized as cured. This is in contrast to the prevailing perception of what constitutes a cure: complete eradication of the virus resulting from a purging process, including the flushing and elimination of the viral reservoir. The researchers in this study propose that pursuing endogenization of the viral genome may prove to be an avenue for achieving a cure in humans.

“We suggest that persistence of integrated HIV DNA is not a barrier, but on the contrary, may be a prerequisite to HIV cure,” the authors write.

To read the Yahoo News story, click here.

To read the study, click here.    October

New HIV Drug Resistance Test Works With Undetectable Viral Load

LabCorp and Monogram Biosciences have developed a new test to detect HIV resistance mutations to antiretrovirals (ARVs). Unlike previous tests, this one works even when an individual has a very low or undetectable viral load. Called the GenoSure Archive, the test should aid physicians in better determining which ARV regimen is the best for their patients living with the virus.

“The launch of GenoSure Archive addresses an emerging need of today’s HIV patients and their care providers, who are increasingly faced with choices to maintain or adjust ARV drug regimens when the patient has low or undetectable plasma virus,” Christos Petropoulos, PhD, vice president of research and development at Monogram Biosciences, said in a release. “GenoSure Archive gives clinicians the specific knowledge needed to better monitor or adjust their patients’ antiretroviral drug regimens. This test helps ensure that HIV/AIDS remains a chronic, manageable disease rather than a terminal illness.”

The test works by amplifying HIV’s DNA from infected cells and then looking for mutations that are linked to resistance to all of the most widely used classes of ARVs. To do so, it references Monogram Biosciences’ database of over 150,00 matched phenotype and genotype test results.

To read the press release, click here.

Countries ready to “Fast Track” response to end the AIDS epidemic by 2030

High-level panel emphasizes fragile five-year window for rapid and massive acceleration of HIV treatment and prevention services. New agreement to reduce cost of viral load tests for HIV to below US$ 10 will improve the quality of life for millions of people on HIV treatment
GENEVA/NEW YORK, 25 September 2014—A new fast-track strategy proposes rapid and massive acceleration of HIV prevention and treatment programmes with a people-centred approach for ending the AIDS epidemic by 2030. This call and new commitments were made at a high-level side event entitled Fast track: Ending the AIDS epidemic by 2030. 
Ending the AIDS epidemic: priority for post 2015 agenda
The high-level side event took place during the 69th United Nations General Assembly and was co-convened by Ghana and Switzerland in collaboration with the Joint United Nations Programme on HIV/AIDS (UNAIDS).  World leaders agreed that ending the AIDS epidemic as a public health threat by 2030 was possible and must be a central agenda of the post 2015 goals.
“An AIDS-free generation is in our reach. It is our responsibility to make it happen. Nations have to unite in this common goal and act together with force of conviction,” said Didier Burkhalter, President of Switzerland. “The objective is clear: end AIDS by 2030!”
Fast Track Strategy—speed combined with location and population
This strategy calls on countries, especially those with high burden of HIV, to provide lifesaving HIV treatment and prevention services as a matter of priority to people most at risk of HIV infection in areas with high HIV prevalence and density of people living with HIV in a short window of five years. Such an approach will drastically reduce the number of new HIV infections as well as AIDS-related deaths to record low levels.
“I believe strongly that ending AIDS should be part of the post 2015 agenda,” said John Dramani Mahama, President of Ghana. “This is an epidemic that no one thought we could end, but now with the progress we see we know it can be done.”
AIDS is not over in any region—30 countries account for more than 80% of new HIV infections that occur each year in the world. Within these countries, the epidemic is often concentrated in large cities, select districts and localized areas. And in each setting, the affected populations vary. A concerted push to reach the specific populations most at risk in these countries and local areas will maximize the gains in preventing new HIV infections and stopping AIDS-related deaths.
Fragile five-year window
The success of the fast-track strategy relies upon countries to frontload investments and step up the pace of delivery of HIV services, especially the roll of out of antiretroviral therapy. This strategy will see the greatest returns on investments.
“I call on countries, the private sector and civil society to seize this opportunity to end the AIDS epidemic by 2030,” said Ban Ki-Moon, United Nations Secretary-General. “This will require innovation, leadership and shared responsibility to ensure that no-one is left behind.”
UNAIDS, together with governments, civil society and other partners, will help countries identify the areas where fast-track delivery of HIV-related services will have the most impact.
“We have a fragile-five year window to ensure that the world is on-track to end the AIDS epidemic,” said Michel Sidibé, Executive Director of UNAIDS. “Seizing the opportunity to fast track the response to HIV will save millions of lives—the cost of inaction is unthinkable.” 
If fully implemented the fast-track approach will avert 18 million new HIV infections and 11 million deaths by 2030. This will have a huge impact on reducing the amount of investment needed for the AIDS response beyond 2020. However, UNAIDS modelling shows that if the targets for 2020 are not achieved until a decade later costs will continue to spiral upwards.
Ambitious 2020 HIV treatment and prevention targets
To get on-track, new targets will focus on closing the access gap to HIV treatment and prevention by setting new targets for 2020. These include a bold target of providing access to antiretroviral treatment by 2020. Target—90-90-90—would enable 90% of people living with HIV to know their HIV status, 90% of people who know their status to access HIV treatment and 90% of  people on HIV treatment  to achieve viral suppression.
“Thanks to the Clinton Health Access Initiative, UNAIDS, PEPFAR and the Global Fund, our negotiations secured reduction of the price of viral load testing not only for South Africa but the whole world,” said Jacob Zuma, President of South Africa. “We now have the tools we need to end the AIDS epidemic.” 
The new agreement on lowering the cost of viral load tests was announced by South Africa, the Clinton Health Initiative, UNAIDS and pharmaceutical company Roche. Viral load tests are essential to monitor the impact of HIV treatment on individuals. The high price of the viral load test is a barrier to its widespread use in low- and middle income countries. With this price reduction, these lifesaving diagnostic tools will become more widely available.
Based on consultations with global treatment experts and regional consultations, UNAIDS also released an issues brief 90-90-90 an ambitious target to help end the AIDS epidemic to support the implementation of the new 2020 HIV treatment target. This document outlines the rationale, scientific evidence and strategy to rapidly expand access to HIV treatment.
In addition to ensuring that no child is newly infected with HIV, a new target of reducing new adult HIV infections from 2.1 million in 2010 to 500 000 in 2020 and to 200 000 in 2030 is proposed. This can be achieved by combining the potential of antiretroviral therapy to prevent new HIV infections with other proven HIV prevention methods such as male and female condoms, harm reduction measures, voluntary medical male circumcision, sexual and reproductive health services and innovative social security programmes such as cash transfers.
“We need to focus on data, mutual accountability and transparency for impact, and put our weight behind HIV prevention, treatment and care interventions that work. We also need to continue setting benchmarks, and I am very pleased that PEPFAR is laser focused on achieving ambitious targets in areas of high HIV prevalence. The challenge is obviously big and obviously important,” said John Kerry, United States Secretary of State.
Zero discrimination - Leaving no one behind
Together with ambitious targets for HIV treatment and prevention, the global goal of zero discrimination needs to be reaffirmed. The success of the AIDS response is primarily due to the unflinching commitment to protecting human rights. Human rights targets are indispensable to ensure that people living with HIV do not face stigma and discrimination, marginalised populations are protected and the right to health becomes a reality.
Key populations—sex workers, gay men and other men who have sex with men, transgender people and people who use drugs—regardless of where they live or the legal status of their behaviour need access to HIV services in close proximity that are free of stigma and discrimination.
Young women and girls in countries with high HIV prevalence need choices to mitigate their vulnerability and risk of acquiring HIV. In sub-Saharan Africa, HIV prevalence among young women and girls is higher than among their male peers.
 “When I think about ending AIDS I dream of wanting to be alive by 2030. I want to see my husband stay free from HIV and my daughter protected from HIV infection,” said Teresia Njoki Otieno, Chair of the International Community of Women Living with HIV. “I do not want to come back here in 2030 and talk about the same thing. We should end this epidemic but we can only do this if we put women living with HIV at the centre.”
AIDS by the numbers
UNAIDS is reporting the lowest levels of new HIV infections this century, at 2.1 million [1.9 million–2.4 million]. In the last three years alone new HIV infections have fallen by 13%.
It is estimated that 35 million people were living with HIV in the world at the end of 2013. AIDS-related deaths are at their lowest since the peak in 2005, having declined by 35%.
New HIV infections among children have fallen by 58% since 2001 and have now dropped below 200 000 in the 21 most affected countries in Africa.
Defining ending the AIDS epidemic
Ending the AIDS epidemic means that the spread of HIV has been controlled or contained and that the impact of the virus on societies and on people’s lives has been marginalized and lessened, owing to significant declines in ill health, stigma, deaths and the number of orphans. It also means increased life expectancy, unconditional acceptance of people’s diversity and rights, increased productivity and reduced costs as the impact of AIDS diminishes.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) leads and inspires the world to achieve its shared vision of zero new HIV infections, zero discrimination and zero AIDS-related deaths. UNAIDS unites the efforts of 11 UN organizations—UNHCR, UNICEF, WFP, UNDP, UNFPA, UNODC, UN Women, ILO, UNESCO, WHO and the World Bank—and works closely with global and national partners to maximize results for the AIDS response. Learn more at unaids.org and connect with us on Facebook and Twitter.

(The following article was published at poz.com )

Midlife Virus
by Tim Murphy
Older people newly diagnosed with HIV can stay resilient. 

Nancy Asha Molock did the right thing. When Molock—a striking, bright-smiled 63-year-old retired Philadelphia schoolteacher—started dating again in 2000 after divorce ended a 17-year marriage that produced two kids, she’d heard the reports that sexually active midlife folks were susceptible to HIV and should wear condoms with partners of unknown status. So when she started dating a fellow her age—whom she became engaged to and who, she often noticed, had a chronic cough—she insisted at first on condoms.

“I said to him, It’s going to be condoms until you have an HIV test,” she recalls. “But he kept putting it off. He said he’d never injected drugs or been with men, and I believed him. He also said he didn’t like how condoms felt. One night,” she sighs, “I caved to affection. And once you allow them not to wear a condom the first time, that’s it.”

Her fiancé’s health further declined. “I found him shivering in front of the computer one morning and took him to the ER.” Sure enough, her fiancé had AIDS. Later, he finally admitted to having been with sex workers, “and I think there’s more he’s never told me,” Molock says. When she tested herself shortly thereafter and found out she was HIV positive, she says she wasn’t surprised. “My doctor said to me, ‘I have some bad news—you have HIV,’” she recalls, “and I said, ‘Okay, what’s the next step?’ My doctor said, ‘Did you hear what I just said?’ And I said, ‘Yes I did, so what’s the next step?’”

Molock still married that man, only to divorce him a few years later, even as she faced coping and living with HIV at 50, an age at which many people (often mistakenly) consider themselves in the clear for sexually transmitted infections. Her story is not an isolated one. According to estimates from the Centers for Disease Control and Prevention, in 2011, the last year for which data is available, nearly 20,000 Americans older than 40 were diagnosed with HIV. That’s 40 percent of the total (around 49,000) for that year. And 16 percent of those diagnoses were in folks over age 50.

Nancy Asha Molock

It’s hard to know how many of those diagnoses reflected recent versus long-term infections. But in 2011, folks ages 40 to 49 made up the highest percentage of those diagnosed with advanced AIDS, suggesting that some folks in midlife go years with HIV before diagnosis. “The older people get, the later they get tested from their point of infection,” says Mark Brennan-Ing, PhD, research director at AIDS Community Research Initiative of America (ACRIA), which specializes in HIV/AIDS in older Americans. “A lot of people over 50 don’t talk to their doctors about sex.”

But for those who find out they are HIV positive, says Brennan-Ing, “It can be really distressing because HIV infection is not something we really associate with mid- and late-life. There’s an off-time aspect to it.”

And Brennan-Ing isn’t just talking about straight women, who might seem less aware than gay men that they’ve been exposed to HIV. He relates the story of a gay man over 50 who worked in the HIV/AIDS field, who did not know that his longtime partner was having unsafe sex outside their relationship. “That man was diagnosed with HIV and felt deeply betrayed by his partner, and the relationship ended as a result,” says Brennan-Ing. “And because this man had been working in the HIV field so long, he felt stupid. A lot of older gay men who are infected feel that way, and that shame can trigger major depression.”

Of course, some older gay men get HIV not unwittingly in a relationship but because, after years of practicing safe sex—often through the worst years of the epidemic—they simply break down, no longer willing or able to use condoms consistently.

Rik Gillette, 63, a data manager for AIDS Services Foundation in Orange County, California, credits having lived a closeted, hetero-married life for keeping him HIV negative in the 1980s and ’90s. But he came out to his wife shortly before she died in 2000, after which he lived the sexually unfettered gay life he’d long desired. In Dallas, he and his roommate would throw festive gay pool parties that often became sex bashes.

“In the heat of the moment, sometimes condoms were not used,” he recalls. “It didn’t even cross my mind—I was just into the fun.” In early 2009, living in Orange County, he had a case of staph infection, which landed him in the emergency room, where he was diagnosed with HIV. “I wasn’t totally shocked, but it was a surprise,” he says, “because I’d tested HIV negative before leaving Dallas and played safe in California, so it must have happened right before I left. I have a good idea who gave it to me—someone I was more intimate with than most.”

Gillette says he doesn’t regret the long-awaited abandon of those pool parties—“just the fact that I hadn’t been more cautious.” As for his HIV diagnosis, “I took it in stride,” he says. “I didn’t see it as a death sentence.”

Still, he admits, “I wasn’t knowledgeable about the disease at all, how it was going to affect my social life, having to disclose my status to guys. It was a whole new coming-out process for me.” Gillette lost the job he had at the time, depleted his savings and ended up nearly homeless until AIDS Services Foundation helped him find transitional housing, let him volunteer there and, thanks to his tech background, eventually hired him. Since then, he’s been doing OK, attending support groups, though he admits, “I’m having issues with companionship at my age—I miss having someone I can cuddle with on the sofa and watch TV.” He doesn’t go on dating websites or to gay bars, though he does find camaraderie singing in a gay men’s chorus.

Rick Gillette
Then there’s the occasional judgment he gets for contracting HIV when he “should have known better.” Says Gillette: “A couple people in my support group have said to me, ‘Why would you make a conscious decision not to use protection?’ They didn’t quite call me stupid, but that’s how I interpreted it. All I can say is, I wanted to experience the joy of the moment. I’m a heavy guy, and the thought that anyone wanted to have sex with me was encouraging.”

A comparable story is told by San Francisco training management exec Jerry Ervin, diagnosed at age 45 in 2009. “I’d stayed HIV negative so long I thought I was Superman and started having condom-free sex,” he says. He points out that HIV hasn’t changed his life much. “I still work and do triathlons.” But he admits he feels “embarrassment” at having gotten HIV later in life.

Also, he only dates HIV-positive guys now, unlike before, fearful of giving someone HIV. Data proving that a positive person on meds with undetectable virus, such as himself, essentially cannot transmit HIV, “hasn’t allayed my fears.” Plus, he says, “I feel inferior with someone HIV-negative, like I’m in a lesser category.” He’s been dating an HIV-positive guy the past seven months, enjoying condom-free sex. “We can talk about our meds together. We’re in the same boat.”

Some older folks experience depression and anxiety after an HIV diagnosis, says Brennan-Ing, adding that ACRIA research has uncovered four key factors that help people stay resilient and move forward. They are, he says:

1. A social support network, or “having people there you can turn to,” whether they are family and friends or folks you meet in groups at an HIV/AIDS agency or a senior center.

2. Spiritual or religious beliefs of some kind. “It helps people make sense out of things that happen to them and move forward,” he says. Plus, he notes, organized spirituality often has a social component.

3. A sense of self-esteem, or what Brennan-Ing calls “environmental mastery,” meaning the sense that one knows how to take steps to make positive change and get one’s needs met.

4. A sense of purpose and meaning. “Feeling like you have a reason for existence is very protective against stigma and loneliness.”

That’s been a huge help for Debra Glover, a Columbus, Georgia, HIV activist who was diagnosed with HIV at age 50 in 2001, having gotten the virus from her high-school sweetheart. “The hardest thing was telling my daughter, who was in high school at the time,” she recalls. “But I prayed on it, and my entire family ended up being supportive.” Now she works to guide people and their families through the HIV diagnosis process, and to educate her region on HIV risk factors and prevention methods. “We’re a small town without a lot of support around this, so I try to be a voice for the silent.”

So does Conneil “Jay” Gavin, 53, of New Brunswick, New Jersey. Diagnosed with HIV in 2006, Gavin attributes his infection to not using condoms properly—“we used petroleum jelly instead of water-based lubricant”—with a former boyfriend who didn’t tell him he was HIV positive. Gavin says that, compared with his Marfan syndrome (a disorder of the connective tissue), his HIV diagnosis has not been that hard to live with, mostly because of the fact that he has the support of his family as well as his church congregation, whom he disclosed his status to. Now he teaches safe-sex workshops with Hyacinth AIDS Foundation. “I want to demolish HIV stigma!” he says boldly. But even he has not escaped it completely; “I have an uncle who cursed me out for leaving my razor in his bathroom,” he admits.

And as for Nancy Asha Molock? In the decade-plus since her HIV diagnosis, she has thrived, retiring from school teaching to travel widely throughout Africa and get involved with the national Positive Women’s Network, whose first leadership summit occurs this September in Florida.

“The network has opened my eyes to a lot of the injustice out there and made me realize things are bigger than just me and what I’m going through,” she says. She’s also trying to start a Philly support group specifically for HIV-positive folks over 50. “We have our own issues,” she says. “We may feel more isolated, we’re not going out to clubs anymore, we may feel that people are judging us because we’re older and ‘should have known better,’ and we may be taking care of children or grandchildren.”

Yes, she admits, she has struggled with dating because of her HIV. “I tend to back off more, and I’ve been rejected over being positive. I have to turn it around and say it’s their loss. Because I think I’m a good person. I have a lot to offer.

“I had a good life before I was positive, and I’m going to continue to,” she asserts. “It’s just a virus. I can’t let it stop me. I’m going to get everything I can get out of life.”

Scientists Devise Method of Snipping HIV From Immune Cells

Researchers have created a genetic treatment that, for the first time, has succeeded in removing HIV from infected human cells, providing hope that the technique may be used as part of a treatment, cure or vaccine for the virus. Publishing their findings in the Proceedings of the National Academy of Sciences, researchers devised molecular tools that delete HIV proviral DNA from infected cells.

When HIV infects a human cell, it integrates its DNA into the cell. The new technique takes what’s known as a “guide RNA,” or gRNA, which hunts down the virus’s genetic material, and pairs it with an enzyme called a nuclease that snips DNA out of the cell. The cell’s own methods of repairing genes then kick into gear, bringing the loose ends of the spliced genome back together. The result: a virus-free cell.

The process succeeded in removing the virus from various types of immune cells that HIV typically targets, including microglia, macrophages and CD4 cells.

To make sure the gRNA, which was built from 20 nucleotides (the basic building blocks of the genetic code), did not wind up integrated into the cell’s genome, the researchers constructed it from sequences that do not appear in the coding sequences of human DNA. This helped avoid any cell DNA damage and mitigated the risk of adverse effects.

“This is one important step on the path toward a permanent cure for [HIV],” study co-lead researcher Kamel Khalili, PhD, professor and chair of the department of neuroscience at Temple University in Philadelphia, said in a release.

The technique might be able to fight other viruses and could be used for an HIV vaccine, since cells that were protected by the combination of the nuclease and gRNA could not be infected.

“It’s an exciting discovery, but it’s not yet ready to go into the clinic. It’s a proof of concept that we’re moving in the right direction,” study co-lead researcher Wenhui Hu, MD, PhD, associate professor of neuroscience at Temple, said in the release.

A next step is to find a way to deliver the therapy to every infected cell. Also, because of HIV’s vast capacity to mutate, therapies may need to be tailored to a person’s particular viral gene sequences.

To read the press release, click here.

To read the study abstract, click here.

BETA-cure-update-250x150Sound science takes time. As Richard Jefferys of Treatment Action Group explained in a recent webinar, “HIV Cure Research—Getting Past the Media Hype,” a number of clinical trials are underway in the quest for an HIV cure, but none of the interventions currently under study are expected to cure people of HIV. Rather, those studies provide essential information to get cure science to “the next round” of development, said Jefferys.
Jefferys and webinar co-host David Evans, director of research advocacy at Project Inform and community advisory board member with the Delaney AIDS Research Enterprise, unpacked the concept of “cure,” outlined the types of cure currently under study, and highlighted key questions at the heart of cure research today.

Defining “Cure”

According to Evans, in cure research, “one of the biggest areas of concern is how we define a cure in the first place, and what that says about people’s hopes and desires.” So what exactly constitutes a cure, and what does “cured” look like in the real world, beyond clinical trial settings?
While acknowledging that definitions of “cure” continue to be refined, Jefferys described the most widely agreed-upon potential types:
  • sterilizing cure would involve total elimination of all replication-competent HIV (that is, HIV that is capable of making more copies of itself) from the body.
  • With a functional cure, the virus may not have been completely eliminated but no HIV replication is detectable and individuals experience no disease progression in the absence of antiretroviral treatment.
  • Remission, the latest definition to enter the HIV cure dialog, refers to control of HIV viral load at low levels (such as below 50 copies/mL) in the absence of treatment.
Timothy Brown, who had both HIV and leukemia and underwent intensive radiation and chemotherapy and received transplanted stem cells from an HIV-resistant donor, appears to represent a sterilizing cure, Jefferys said. The most ultrasensitive tests have detected no replication-competent HIV in his tissues in the eight years since his radical treatment. (Timothy Brown tells his own amazing story here.)
However, the treatment Brown received was in itself life-threatening, and is not seen as a scalable approach to curing HIV. In addition, a sterilizing cure is the most difficult to prove, involving extensive tissue sampling and testing with the most sensitive assays to look for viral RNA, HIV’s own genetic material: “It’s a huge challenge to figure out how to measure such tiny amounts of HIV RNA,” Jefferys noted.
“We may never get to a place where we totally eradicate the virus in most people,” added David Evans, “but instead place them in a kind of remission, whereby HIV is fully controlled, but not causing much harm without the need for antiretroviral drugs.”

Current Approaches to Curing HIV

Evans detailed the current major avenues of HIV cure research, and progress to date.

“Shock and Kill”

One of the biggest obstacles to curing HIV is posed by viral reservoirs, cells harboring “latent” or non-replicating HIV. Because these latently infected cells do not display pieces of HIV on their surfaces, Evans explained, the immune system cannot not recognize and destroy them.
A handful of anti-cancer drugs belonging to a class known as histone deacetylase inhibitors (HDAC inhibitors for short) alter viral genes, allowing the body to recognize infected cells. HDAC inhibitors are being tested for their ability to force latent HIV out of hiding, then kill infected cells—a strategy known as “shock and kill.”
When researchers tested the HDAC inhibitor vorinostat (also known as SAHA) with once-daily dosing over several days, they saw a rise in viral RNA—“what we want to see,” as Evans put it, when testing a drug to shock the virus into the open. However, the increase was only temporary, and HIV DNA—the genetic material produced when HIV replicates—did not decline, indicating that no “kill” had occurred. Two clinical trials are currently underway to address the safety and efficacy of vorinostat for draining HIV reservoirs.
Another HDAC inhibitor, panobinostat, launched a media frenzy when researchers reported evidence that the drug induced HIV replication in an early-stage clinical trial; however, results on viral DNA are not yet available from the research team in Denmark, Evans stated. A trial of the HDAC inhibitor romidepsin is also underway, with results anticipated in late 2015.

Stem Cell Transplantation

The “Boston patients” made headlines in 2012, when researchers reported on two men who underwent stem cells transplant procedures similar to Timothy Brown’s, but with a few key differences: The two men had “gentler” chemotherapy and no full-body radiation, so they retained host immune system cells; they received donor cells that were susceptible to HIV infection, unlike the HIV-resistant cells Brown received; the Boston men were themselves heterozygous for the HIV-blocking mutation, meaning they each had a single copy of the protective gene; and both continued to take antiretroviral drugs throughout and following their procedures.
Up to four and a half years after the transplants, the research team could detect no HIVusing highly sensitive tests, and the two individuals and the research team agreed to an analytical treatment interruption to see whether the virus would return. “Initially, things looked really good,” noted Evans in the webinar. But within weeks to months of stopping antiretroviral therapy, the virus returned. Both men saw huge spikes in their formerly undetectable viral load, Evans explained, and both experienced retroviral syndrome—the immune system’s reaction to unchecked viral replication, typically seen in people recently infected with HIV.
“I think what this is telling us is how difficult it is to actually kill the virus,” said Evans. Both men were able to get the virus under control again with antiretroviral therapy (ART).

Extremely Early Treatment

As reported previously, the “Mississippi baby” was diagnosed with HIV using RNA and DNA tests, which detect HIV’s genetic material rather than antibodies to the virus (which can be carried over from the mother). She was started on triple-drug antiretroviral treatment just 30 hours after birth, and within a month, her viral load was undetectable. She continued on treatment until around 18 months of age, when she was lost to care for several weeks. When the child was brought back for medical visits at roughly two years old, she had been off treatment for five months—yet she had an undetectable viral load.
In March 2014, when the child was approximately three years old and had been off ART for 23 months, Persaud reported at the 21st Conference on Retroviruses and Opportunistic Infections that “there has been no detectable rebound in plasma virus using standard clinical assays with detection limits of less than 20 copies/mL,” and suggested that the child is “in remission.”
Persaud also reported on a second infant, born in California, who was started on ART just four hours after delivery. HIV infection was confirmed by the same HIV RNA and DNA tests administered to the Mississippi baby. Nine months old at when Persaud reported the case, the Long Beach child had had no detectable viral RNA or DNA since day 11 and day 6 after birth, respectively. However, the child remains on ART. “These tests that we’re doing are really being done under antiretroviral treatment cover, quite unlike the Mississippi child,” Persaud said in a press conference. “Having said that, at nine months of age, there’s less than 2 copies of HIV DNA [per mL in blood cells] and we have not detected a replication-competent reservoir,” she added.
In the May 8 webinar, Evans also noted that five Canadian children born with HIV and treated within 24 hours after birth are being followed by cure researchers. All had undetectable viral load to as old as eight years of age; however, all remain on antiretroviral therapy. One child whose treatment was interrupted saw the virus return.
If most of these children are still on treatment, asked one webinar participant, why are we even talking about them? “They’re being discussed because they don’t have any detectable virus, no matter how hard we look,” explained Evans. An as Persaud put it in March, “There’s a signal here that giving very early antiretroviral drug treatment in neonates really restricts HIV spread [in the body], to the point that it becomes difficult to detect infection.”
Also as previously reported, the VISCONTI Cohort in France includes adults who began ART within days to weeks after infection with HIV, remained on treatment for several years with undetectable viral load, and have now been off ART for as long as ten years with no major viral rebound.
As Evans emphasized, these individuals are genetically distinct from “elite controllers”—a small population of people whose immune systems are able to keep HIV in check without treatment. The cohort originally included 14 individuals, but Evans noted that roughly 20 are being followed today.

Key Questions

Cure trials to date have provided essential data that point the way for future research. However, as Richard Jefferys explained, many significant questions remain that have important implications for the way we pursue cure science.
For example, we know draining viral reservoirs is key—but by how much? “How much do you have to reduce the HIV reservoir to really have an effect, and not have it return off antiretroviral treatment?” asked Jefferys. Long-term monitoring of trial volunteers will be essential as more studies tackle viral reservoirs.
Other major questions highlighted in the webinar included:
  • Can combinations of interventions be used to reverse HIV latency and eliminate infected cells?
  • Are there immune responses that can be induced or revived that would lead to HIV control?
  • Can gene therapies generate enough HIV-resistant cells to cure infection?
  • Can early treatment lead to a cure in more children? In adults? And how early is early enough?
  • How and when can we confidently deem a person “cured”?
To explore these and other questions, Jefferys added, the Forum for Collaborative HIV Research will host a public meeting on June 17 in Washington, DC. The meeting will be webcast to allow for greater participation; click here for details and to register.
The webinar concluded with a thought-provoking Q&A session, in which one participant questioned the wisdom of funneling limited resources into cure research rather than expanding access to HIV treatment. “As good as antiretroviral therapy is, and as close as we are getting people to a place where they would live out a natural, normal life span, we still do see long-term toxicities and health concerns because of that low level of virus that is able to persist,” stated Evans. A scalable cure or way to get people into HIV remission in the absence of ART, he said, would be “a net win for all.”

Breaking for March:
CNN) -- The first time, it happened almost by accident.
Just hours after delivery, a baby born with HIV in Mississippi was given high doses of three antiretroviral drugs. More than three years later, doctors say the little girl has no evidence of the life-threatening disease in her blood, despite being off medication for nearly two years.
Now doctors say another child born with the virus appears to be free of HIV after receiving similar treatment. The case report was presented at the annual Conference on Retroviruses and Opportunistic Infections in Boston this week.
The girl was delivered at Miller Children's Hospital in Long Beach, California, last summer to a mother with AIDS. Doctors gave the baby high doses of antiretroviral drugs -- AZT, 3TC and Nevirapine -- four hours after birth. Eleven days later, the virus was undetectable in her body and remained undetectable nine months later.
The California baby is still on antiretroviral treatment, so it's too soon to tell if the child is actually in remission. While doctors around the world are trying to duplicate the Mississippi case, more research needs to be done before new standards are implemented for treating babies born with HIV.
"This has to be done in a clinical trial setting, because really the only way we can prove that we've accomplished remission in these cases is by taking them off treatment, and that's not without risks," Dr. Deborah Persaud, a virologist with Johns Hopkins Children's Center, said during her presentation at the conference.
A clinical trial designed to test the effectiveness of this early treatment technique on infants born with HIV is set to begin in the next couple of months, Persaud said.
The results could be a game changer in the fight against AIDS.
The Mississippi baby
The child in Mississippi was born to a mother who received no prenatal care and was not diagnosed as HIV-positive herself until just before delivery, according to a case report published in October in the New England Journal of Medicine.
"We didn't have the opportunity to treat the mom during the pregnancy as we would like to be able to do, to prevent transmission to the baby," said Dr. Hannah Gay, a pediatric HIV specialist at the University of Mississippi Medical Center.
Doctors administered the antiretroviral drugs 30 hours after the girl was born in hopes of controlling the virus. Within a couple of days, Gay confirmed the child was HIV-positive. She said the baby had probably been infected in the womb. The child remained on antiretroviral drugs for approximately 15 months. Her mother then stopped administering the drug for some reason, Gay said.
In March 2013, researchers announced that the girl was the first child to be "functionally cured" of HIV. A "functional cure" is when the presence of the virus is so small, lifelong treatment is not necessary and standard clinical tests cannot detect the virus in the blood.
Gay told CNN the timing of intervention -- before the baby's HIV diagnosis -- may deserve "more emphasis than the particular drugs or number of drugs used."
"Prompt antiviral therapy in newborns that begins within days of exposure may help infants clear the virus and achieve long-term remission without lifelong treatment by preventing such viral hideouts from forming in the first place," Persaud told CNN last year.
High-risk exposure
Researchers have long known that treating HIV-positive mothers early on is important, because they pass antibodies on to their babies.
All HIV-positive moms will pass on those antibodies, but only 30% will transmit the actual virus, said Dr. Katherine Luzuriaga, an immunologist at the University of Massachusetts who worked closely with Gay. And HIV-positive mothers who are given appropriate treatment pass on the virus in less than 2% of cases.
"So all babies are born antibody-positive, but only a fraction of babies born to HIV-positive women will actually get the virus, and that fraction depends on whether the mom and baby are getting antiviral prophylaxis (preventive treatment) or not."
Newborns are considered high-risk if their mothers' HIV infections are not under control or if the mothers are found to be HIV-positive when they're close to delivering.
Usually, these infants would get antiviral drugs at preventive doses for six weeks to prevent infection, then start antiretroviral therapy, or ART, if HIV is diagnosed.
ART is a combination of at least three drugs used to suppress the virus and stop the progression of the disease.
But they do not kill the virus. Tests showed the virus in the Mississippi baby's blood continued to decrease and reached undetectable levels within 29 days of the initial treatment.
The 'Berlin patient'
Researchers say the only other documented case of an HIV cure is that of Timothy Brown, known as the "Berlin patient." In 2007, Brown, an HIV-positive American living in Germany, was battling both leukemia and HIV when he underwent a bone marrow transplant that cured not only his cancer but his HIV.
In an interview last year, Brown told Dr. Sanjay Gupta, CNN's chief medical correspondent, that he was still HIV-free.
"I've been tested everywhere possible," said Brown, who now lives in San Francisco. "My blood's been tested by many, many agencies. I've had two colonoscopies to test to see if they could find HIV in my colon, and they haven't been able to find any."
But Brown's case is apparently unique.
And the procedure, which is extremely dangerous, won't work in most patients because the bone marrow he received had a special genetic mutation that made the stem cells in it naturally resistant to the virus.
Researchers tell CNN only 1% of Caucasians -- mostly Northern Europeans -- and no African-Americans or Asians have this particular mutation.
In June, five years after he was "cured," reports surfaced that "traces" of the virus had been found in Brown's blood.
Even then, some HIV experts said that doesn't matter, that he's been cured. In fact, many AIDS experts said they believe Brown has experienced what's called a "sterilizing" cure, meaning the virus has been eliminated from the body entirely.
In July, Boston researchers said two HIV patients showed no sign of the virus in their blood following bone marrow transplants. However, researcher Dr. Timothy Henrich said in December that the virus had returned. 

 High-dose supplementation with selenium and vitamin E can raise the risk of high-grade prostate cancer among certain men. This is of notable relevance to people living with HIV because of a recent study that found that supplementation with particular combination of multivitamins, including vitamin E, as well as with selenium, could slow HIV disease progression among those who are treatment naive and have a CD4 count above 350.

Publishing their findings in the Journal of the National Cancer Institute, researchers conducted a randomized, placebo-controlled trial involving 35,000 men who received high-dose vitamin E (400 IU per day), high-dose selenium (200 micrograms per day) or both. Designed to run for 12 years, the study started in 2001 but was halted early, in 2008, because it was apparent that selenium offered no protection against prostate cancer and it appeared that vitamin E might raise the risk. The men were then followed for an additional two years.

Among the men who started the study with a high level of selenium and who then took high-dose supplements of the element, the risk of prostate cancer increased by 91 percent. Their selenium levels became toxic.

The men who started with low selenium levels and who then took only high-dose vitamin E supplements raised their risk of prostate cancer by 63 percent and their risk of high-grade prostate cancer by 111 percent. Among the low-selenium participants, taking selenium in addition to vitamin E actually protected against vitamin E’s harmful effects.

“Many people think that dietary supplements are helpful or at the least innocuous. This is not true,” said corresponding and first author Alan Kristal, DrPH, a faculty member in the public health sciences division of Fred Hutchinson Cancer Research Center and the study’s lead author, said in a release. “We know from several other studies that some high-dose dietary supplements—that is, supplements that provide far more than the daily recommended intakes of micronutrients—increase cancer risk. We knew this based on randomized, controlled, double-blinded studies for folate and beta carotene, and now we know it for vitamin E and selenium.”

To read the press release, click here.

   New Anti-HIV Compounds Discovered (January 2014)

Researchers at the University of Minnesota have identified a series of novel compounds that combat HIV and may one day lead to new options for antiretroviral treatment. Publishing their findings in the Journal of Virology, the investigators discovered five compounds called ribonucleoside analogs that in laboratory studies either blocked replication of HIV at the point in its life cycle called reverse transcription or that caused the virus to mutate into extinction.

“It’s a counterintuitive finding,” said Louis Mansky, PhD, a virologist at the University of Minnesota and one of the study’s authors, said in a release. “These ribonucleoside analogs were not generally thought to be associated with affecting HIV DNA synthesis—a critical step in virus replication. We don’t yet know all the details for how these particular compounds stop the virus in its path.”

If research pans out, these findings may lead to new, cost-effective HIV treatments and a means to combat resistance to today’s antiretrovirals. Ribonucleoside analogs are less expensive to produce than the deoxyribonucleoside analogs currently in use and for which they might provide an alternative.

To read a release on the study, click here.


Read More on the Cure

If this slide show has piqued your interest and you want to learn more about the search for a way to stop HIV/AIDS once and for all, take a look at the following articles:

This article was provided by TheBodyPRO.com.

Latest as of March 2014

University Of Miami Researchers Believe They Have Developed A Promising AIDS Vaccine

A research team at the University of Miami say they have developed a vaccine that triggers an immune system response strong enough to kill a model AIDS virus in mice.
Geoffrey W. Stone, a UM assistant professor of microbiology and immunology who led the research study published in February’s Journal of Virology, says the vaccine is still in the early stages of development but his team has already had some very dramatic results.”
Stone’s research team has taken a different approach to the standard vaccines that introduce a virus protein that triggers an immune system response. Instead, the UM vaccine uses a more targeted approach.
What we have done is we’ve attached it on to the guided missile that brings it to the bad cells but brings it to the good cells, cells called dendrite cells, and helps those cells do a better job,” Stone told WSVN.
The vaccine targets specific cells, delivering an important warning to the immune system. “These cells are very sensitive to danger signals, the things that happen when you get a cold. These cells get activated. If you don’t activate them, they don’t work well,” said Stone. 

According to the University of Miami press release:
The research, conducted at the Miller School’s Miami Center for AIDS Research, is being led by Geoffrey W. Stone, Ph.D., assistant professor of microbiology and immunology, and the results are published in the February 2014 issue of the Journal of Virology. The key finding is that the vaccine developed by Stone’s team, when targeted to a unique receptor in the immune system, can generate unprecedented T cell responses to HIV. The receptor involved is called CD40, and the vaccine uses a special form of its natural binding protein, CD40 ligand (CD40L), to enable important immune cells called dendritic cells to detect the presence of HIV proteins.
Dendritic cells are the gatekeepers of the immune system. They collect and process foreign proteins, known as antigens, and then alert the rest of the immune system to the invader. An essential step in this process is that the dendritic cells must become activated through the CD40 receptor.
Stone and his collaborators have found that directly coupling the foreign protein antigen to a special form of CD40 ligand leads to extraordinarily strong CD8+ T cell responses in mice. In the case of an HIV protein, the vaccinated mice were able to completely fend off infection by more than 10 million model viruses containing the HIV protein antigen. This type of extreme immune protection, called sterilizing immunity, is rarely seen in vaccine studies.
“The key to the vaccine’s effectiveness is that it contains a new form of CD40 ligand connected to the foreign protein antigen,” explained Stone. “This means that the dendritic cell both receives the antigen and is activated by its CD40 receptor at the same time.”
The research offers hope for the development of vaccines for other diseases, as well. Large numbers of CD8+ T cells can also protect against influenza, malaria and cancer, but no current vaccines generate enough CD8+ T cells to be effective.
“Vaccine-induced protection has been very difficult to achieve,” said Stone. “This new vaccine design takes us to another level in stimulating the immune system to produce CD8+ T cells. The next steps will be to test the vaccine in monkeys, and then in humans.”
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institute on Drug Abuse.


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