Showing posts with label HIV Cure. Show all posts
Showing posts with label HIV Cure. Show all posts

December 7, 2016

No HIV Cure in 2016 but Something is Likely to Come in 2017


New study shows excellent results in a study on monkeys and a med being used now. Next stage is already in progress testing it on volunteers. There is a drug company in Japan who is had good results but they are not the only ones working on it. They made the International news because they are ready to move to the next stage and because is with a drug that has been used to treat another condition.

The surprising results have come from a study in monkeys involving an antibody used to treat Crohn’s disease.
Who has done the research?

 The study comes from the lab of Dr Anthony Fauci, the director of the National Institute of Allergy and Infectious Disease in the US.

He has made research into HIV-AIDS his life work.

He is overseeing clinical trials testing whether the drug, made by Japanese drugmaker Takeda, can control HIV without the need for ongoing treatment.

The research builds on efforts by several teams to produce sustained remission of HIV-AIDS after suspending antiretroviral therapy (ART).

With the exception of one group of people in France, known as the Visconti cohort, all patients who have stopped taking ART after some form of treatment have seen the virus return. 

The drug
The drug, Entyvio, is an antibody engineered to attack a specific protein.

Known generically as vedolizumab, it is approved in more than 50 countries for ulcerative colitis and Crohn’s disease.

This occurs when the immune system attacks the intestines.

 How many HIV patients are there around the world?

 An estimated 36.7 million.
When will we have the results?
Not until late 2017 or early 2018.
What is a “functional cure”?
A treatment that puts the disease in sustained remission, allowing patients to skip the daily cocktail of pills they must take to keep their disease in check.

The hope would be that, eventually, instead of having to take daily medication, patients could get a shot or infusion every few months that would keep their virus in check. 

What are the HIV-AIDS specialists saying?

 There is optimism about the work, but they remain cautious.

Many promising drugs have worked extremely well in monkeys but have failed to work in people.
Are there any other trials ongoing?

Fauci’s study is one of several early stage clinical trials testing new drug and antiviral combinations that could help patients keep HIV in check and raising hopes for a “functional cure” that puts the disease in sustained remission.

A second trial combines a therapeutic vaccine from Johnson and Johnson with an immune system booster from Gilead Sciences.

Both are especially promising because they involve products already tested in people, which could speed up development time if they are worked.

Other ideas are also being worked on, including a full-scale human trial that was launched in South Africa this week (November, 2016).

Research on stopping the virus includes studies involving human antibodies that neutralise HIV, as well as a vaccine that uses a herpes virus to train the immune system to fight HIV.
What Dr Fauci says

 Dr Fauci says what they have found in monkey models is promising. They are now testing to see if this can be replicated in the first human trial.

“We clearly induced something in the monkeys that is chronically, over one to two years, suppressing the rebound of their virus.”

“We don’t know yet what that is. We don’t know what type of response. We certainly are going to be working in non-human primate monkey models as well as in the humans once we get data from this study to try and figure out what the mechanism is.”

“But the first and important thing we need to do is see if we get the results in the humans that we saw in the animals and that is the reason you do a clinical trial.”

“We will need to wait and see what happens in the human system.”

Fauci says the advances in the treatment of AIDS over the last 30 years have already been astounding.

“We have gone from uniformly-fatal living no more than 12 or 15 months to someone living almost a normal life span.”

December 2, 2016

Sex Was Deadly-One Pill Changed That-Still Some Don’t see the Miracle Pill and Fall Overboard

 If where you live there is access to PrEp you have no excuse to put your self to becoming HIV positive, the health system thru the expense and your next partner that you might give it to.  If you forget to take a pill now if you are sexually active you will also forget to tell your partner about being  exposed and so the virus will live on.                                                                      

In late 2014 I received an email from one of New York City's largest sex parties for gay men. Usually, the email would have contained this: a time, an address, a dress code, the price. The party had long been condoms-only, but a new safe-sex provision had just been added: "If you do have condomless sex it is assumed that you are on PrEP/Truvada or undetectable."

I wouldn't have noticed this email if it hadn't been for a response from New York's one remaining condom-only party. This wasn't an invitation but a statement of policy, an email unlike any sent previously or since. Safe sex is an important project, it argued, and condoms are the only way to be safe. The second party remains condoms-only, and is still alone in this decision. It feels now like a holdover from a different time.

My generation of gay men came after the plague but before the pill. What I knew was that fifty thousand people died in the U.S. in 1995. I was thirteen. What I knew was that sex kills, that no pleasure is ever free of worry, of death. The first thing I learned about sex was Kaposi's sarcoma lesions, gaunt thirty-two-year-olds on TV. I became a gay man and a scientist with a background in microbiology and biochemistry. Viruses have always fascinated me for being so complex and yet so simple, for being so deadly with so few genes.

But HIV didn't just kill bodies. It killed a type of sex as well, a type of pleasure. It erased the possibility of my body and another meeting, one moment, without my mortality there too, watching. Sex is this: another body, my body, my mortality, all naked for me to see. I knew about HIV and death before I knew I was gay. I knew about death then, and that being gay might be deadly, and now I sleep with men.
HIV has never left me. I'm nostalgic for the pre-HIV era I never knew. Our image of those years is ambivalent: You could give head in abandoned buildings by the piers, but anything like a relationship seemed impossible to so many, the notion of gay marriage laughable. Gay people weren't often permitted relationships in a world so threatened by our bodies and how we use them. Now we can get married, but — thanks to HIV — we've lost the notion of pleasure without worry. I worry. I only have unprotected sex when in a monogamous relationship. Even then, who knows? Everyone cheats, even straight people.

Those who lived through or were born into the 1980s became a generation afraid of love and the sex it would bring. The writer Hilton Als, referencing the garbage bags that early AIDS victims were stuffed inside, wrote, "I did not say I loved him....If I did, wouldn't that end up in a garbage bag, too?" Even after HIV became less of a death sentence, I always viewed it fatalistically. Being positive would make it harder — I always felt — to find love and trust and sex. I had reservations about dating someone who was HIV-positive; I knew that if I were positive others would have the same reservations about me. If there were a pill for my worry, I would take it, a cure not for an infection of the body but for the traumatized mind. I would take this pill now, and I would never stop.

Some definitions: MSM: men who have sex with men, a term devoid of political or social overtones (unlike, say, "gay" or "queer"). MSM are the community most at risk for new HIV infection. PrEP: pre-exposure prophylaxis. PrEP is a pill taken by HIV-negative people to maintain their status. Truvada: The one pill approved for PrEP. It has been used as a component of HIV therapy since 2004, but was only approved for PrEP in the HIV-negative in 2012. In this article, "Truvada" refers to the drug used specifically by those who are HIV-negative, a shorthand that is almost universal in New York's gay community. Undetectable: An undetectable person is HIV-positive but controlling their infection with antiretrovirals. New research shows that their likelihood of communicating the virus is essentially zero.

Truvada came on the market four years ago, in 2012 , but prescriptions didn't start taking off until early 2014. Gilead Sciences, the company that makes and sells Truvada, reported earlier this year that eighty thousand to ninety thousand people were on PrEP. Twelve and a half thousand people in New York State have filled prescriptions, the overwhelming majority in the city. The number of individuals starting PrEP has increased exponentially, rising fivefold in two years, from the end of 2013 to the end of 2015. A survey by New York City's Department of Health estimates that 29 percent of MSM ages eighteen to forty in the city are already on PrEP.

For one week, those numbers included me. I wasn't having sex with a stranger. I was having sex with my ex. He'd been in and out of my life after he'd gone away for a month and I'd found evidence he was cheating. A part of me had always known.

We'd been having unprotected sex for a year. I've always had unprotected sex with my boyfriends, a sign that we cared for each other, that we had built something like trust. I insisted on couples trips to the free clinic after three months of monogamy. I loved this man in part because his sex seemed so free, so out of my control. I begged him not to put me at risk. I told him my body was in his hands. He looked me in the eye and said I could trust him. I did trust him. After I caught him cheating, we used condoms. I got tested. He said that he never had raw sex with anyone but me, that it was an intimacy I alone had earned. I believed he was telling the truth. I trusted that he only cheated safely.

My ex wanted another chance. He wanted to have raw sex again. So one of us — I don't remember who — suggested PrEP. This was in 2014, when hardly anyone knew about Truvada. PrEP and undetectable were not yet listed as safe-sex options in hookup apps. Gay activists still called it a poison, a party drug. This pill offered the promise of bringing us back together. Truvada was more certain than his word.

We both started swallowing that big, blue pill once a day.

A week later, without touching him much at all, I was on my way out of his life. PrEP made space for me to consider raw sex with him again, but I realized that it wasn't HIV that made him unsafe. Maybe for the first time in my life, I wasn't afraid of HIV. I was afraid of him. There was no cure for the damage we had done to each other. So I left, and I tried to stay gone.

Truvada is not one drug but two: emtricitabine and tenofovir disoproxil fumarate. HIV pills contain multiple (usually three) antiretroviral drugs. This is because HIV mutates rapidly to become resistant to any one therapy. The likelihood of a single virus simultaneously acquiring resistance to two or three drugs is the product of the individual probabilities, a number that approaches zero without ever reaching it.

People at high risk for HIV infection — sex workers, MSM, those with multiple partners — can take Truvada and have unprotected sex with little risk of contracting HIV. There is a 96 percent reduction in HIV transmission for those who take the drug four times a week. For daily use, the reduction is 99 percent. In one key study, none of the participants contracted HIV. Another option — post-exposure prophylaxis, or PEP — can be taken after a broken condom or risky sex. These drugs stop the virus from replicating before it manages to find and infect T cells. The virus never becomes a part of us.

In preventing the transmission of HIV, PrEP is at least as effective as condoms. Condoms reduce the risk of HIV transmission through anal sex by 70 percent with consistent and proper use. For men who don't use condoms consistently — and according to studies, most men don't — the difference in rates of HIV transmission between sex with and without condoms is not statistically significant.

Those who remain HIV-negative while on PrEP will have antiretroviral medicine consistently in their bloodstream and no virus in their blood. Undetectable people have antiretroviral medicine in their bloodstream and no virus in their blood. In terms of HIV transmission, there is no reasonable distinction between those who are HIV-negative and on PrEP and those who are HIV-positive and undetectable.

For many years there was a respectability politics of condoms. Truvada was vociferously opposed by traditional gay health organizations. Michael Weinstein, the head of the AIDS Healthcare Foundation, continues to campaign against it. The opposition to Truvada seems to have made Gilead cautious about marketing it. Though the drug has been available for four years, Gilead has started to underwrite advertising only in the past few weeks. Paranoia about PrEP remains, often driven by the idea that other infections (chlamydia, syphilis) will rise without condom use. Bacterial STIs did increase in 2015, though it's impossible to connect that increase to Truvada. In effect, much of the rhetoric about STIs continues a long history of pathologizing gay sex, particularly raw gay sex, now that we can no longer rely on HIV alone.

When single, I use condoms consistently. I believed this: Responsible, self-loving, caring, good gay men use them, always. I wanted to be that type of man. I was shocked, talking to my straight friends, to learn that they had unprotected casual sex. Gay men were considered unsanitary even before HIV. Our vice president–elect thinks us unfit to work because of our diseased bodies. We have to constantly prove to the world that we aren't, in fact, sexual monsters, deviants. Straight people don't carry the same burden of politics, the same history of HIV, into the bedroom.

In the era of HIV activism, gay sex was central to the conversation. HIV was a sexually transmitted disease; how we fucked was how we lived or died. In the fight for gay marriage, we willingly hid our sex. An ex-partner of mine worked at GLAAD, where he trained people to say "gay" and not "homosexual," because the latter puts the word sex in people's faces. The fight would be easier if people didn't imagine the icky things we do in the dark. We won the right to marriage by convincing straight nuclear families that our love is just like theirs. Our sex, too: three times a month, monogamous, missionary, seven minutes, safe.

But there's always been a tension. Queer people are a sexual and cultural vanguard. Anal sex is kind of our thing; now sitcoms joke about straight couples pegging. We had Grindr for years before Tinder popped up. We've been doing monogamish since basically forever.

Gay and HIV activists fought conservative institutions — public schools, the Catholic Church — to make condoms widely available and to train people how to use them. In a world where everyone was dying, condoms were the only way to stay alive. They worked. For decades, condom culture was a type of care among gay men. As we approach four years of a Trump administration, this fight against conservative institutions might be beginning anew. But condoms may have a cultural significance that now surpasses their usefulness in public health and public policy.

I bought into the politics that binds HIV and gay-marriage activism: that condoms matter, that sex must be contained, safe, respectable. I was raised Catholic and always had been a little afraid of my own sexuality. I thought myself better-than because I'd always used condoms. I looked down on my friends who didn't. Of course humans — of all sexualities — slip up. Of course people are going to find pleasure in doing the very thing they've always been told not to do. Sometimes we want things from love, from sex, precisely because they aren't safe. I wanted my ex; he wasn't safe. I always suspected he was cheating; we had unprotected sex anyway.

The conventional narrative of the past three decades is that we survived the plague. Then we got marriage, an assimilation into an institution that I always found too narrow for most relationships, even straight ones. What we lost was the freedom of queer sex, queer sluttiness, queer rage, raw sex, queer separatism, hedonism, and free queer love, which might not look like straight love at all. HIV gave gay men who believed in respectability, modesty, and monogamy the upper hand. Marriage used that respectability to gain legal rights. Truvada might be a step toward a new sexual liberation — sex parties, singles and swingers, threesomes even for committed couples — and away from the condoms that made our sex safer not just physically but culturally. No wonder it makes people, gay and straight alike, uncomfortable.

AIDS Taught Me Sex Was Deadly. A Pill Changed That 
Truvada is nothing special, nothing new. The antiretrovirals in it have been used for decades. The difference is the bodies the drugs are put inside, now HIV-negative, no virus in residence, now not ill but pre-ill, infected only by the type of sex we have.

The pill's out-of-pocket cost is roughly $18,000 a year. Truvada is made by only one company, Gilead. One common criticism of PrEP is that it requires HIV-negative people to take very expensive pills whose side effects are not insignificant. PrEP, the argument goes, turns gay sex into a profitable (and therefore palatable) enterprise in the age of late capitalism, where everything is moral if it's making someone rich. Gay sex parties aren't sinful debauchery; they're added value for Gilead shareholders.

The rebuttal is that PrEP works. It's most likely less expensive, and involves fewer years of dealing with side effects, than taking antiretrovirals for a lifetime, as those who are HIV-positive must. Yet $1,500 a month for the option of sex uncontaminated by fear of HIV is a high cost for an individual or society to pay.

Gilead has a program that provides free drugs to those without insurance, and there is a co-pay assistance program as well. Theoretically, anybody should be able to get Truvada at low cost. In practice, it's not that simple.

As I was writing this essay, I had dinner with a friend who had been on Truvada but who had recently had to stop taking the drug. He hit the yearly cap — $3,600 — for the Gilead co-pay assistance program and his co-pay, he said, was as high as $500 a month. With private insurance and a very high co-pay, he was — in terms of access to Truvada — in a worse position than those who have no insurance at all.

"I just want to be able to have sex again," my friend told me. He's single and mostly uses online apps for sex and dates, both. He was having a hard time finding men who would have sex with condoms. For my friend, in 2016, PrEP feels necessary to have sex. He wouldn't have unprotected sex without it, and hookup culture — according to him — has moved on. Condoms are no longer the norm. This does feel new.

I knew the city was building a program to help people with private insurance who max out the Gilead co-pay program. I had met with Dr. Demetre Daskalakis, the head of New York City's HIV prevention campaign, to talk about condoms and PrEP and the city's programs. We'd discussed people in my friend's situation. I spent the next two days on the phone with a full alphabet of agencies: first 311, then HASA (only for the HIV-positive) and ADAP (doesn't cover PrEP), then my city-associated HIV clinic. Nothing. Then state programs, PrEP-AP and the PrEP hotline; then PAN, then Xubex.

On hold listening to badly performed classical music I thought, This is how bureaucracy kills: to Bach. I'd spent months researching PrEP, and I couldn't help my friend. Once I'd exhausted all the options, I reached back to Dr. Daskalakis, hoping for a nudge in the right direction. Yes, the city knows about the PrEP donut hole for the underinsured. Yes, they are hoping to develop a solution. No, there is nothing yet. It's been months since my friend has taken Truvada and months, too, since he's had sex.

Truvada offers sex without worry for fifty dollars a pill. People live and die on the basis of a brief conversation at a clinic about whether and how to sign up. Fifty percent of black MSM are HIV-positive or are likely to be in their lifetimes. New York City is majority-nonwhite. In some places people are still — against medical and epidemiological evidence — going to jail for fucking while HIV-positive. Many still blame an HIV-positive person for their risk when both partners consent to unprotected sex. Even in New York, where the city government is committed to PrEP and stigma-free HIV policy, there are people who fall through the cracks. Outside of this city, those with the least access to PrEP will be people — queer people, poor people, people of color, people in prison, people in rural towns — who have always been excluded from healthcare.

And that is what HIV care looks like before Donald Trump starts running the federal government. Our vice president–elect has led the drive to defund Planned Parenthood — even as the closure of a Planned Parenthood testing center in his home state inflamed a major HIV outbreak.

The coming years could make geography matter even more than it already does — things like PrEP may be accessible in New York and entirely unavailable in rural Indiana. More than five hundred thousand people in America know they're HIV-positive but aren't on treatment. This is more than half of all people living with HIV. A friend of mine has a cousin in a deep-red state dying of AIDS, right now, today. He has KS lesions, he's unlikely to live much longer, he often can't get drugs, and when he does take medicine he tells his relatives only that he has "cancer." This isn't the story we're telling ourselves, and it's not one we often hear.

When PrEP was introduced, we all wanted to know: Would it change behavior? Would it lead to a world where condom use dwindled and raw sex became — again — the norm? Early research showed that PrEP users didn't decrease their condom usage. People on PrEP weren't more likely than they were before to have raw sex, they were just more protected in their actions.

More recent studies suggest otherwise. My experience and the experience of my friends also hints at a culture shift. Almost everyone I asked who still uses condoms has a story of someone backing out of a hookup if condoms were to be used. People are having more raw sex, and they're more open about it. They advertise it on apps. They talk about it with their friends. I see it now, and I didn't see it much before.

I've spoken to dozens of people, on and off the record, about PrEP. Sitting at my kitchen table with three gay writers, none of whom were taking PrEP, I realized that all the people I've talked to — whether they are taking the drug or not — are making a difficult and informed choice about their body, their pleasure, their risk, their sex. Some are using PrEP as a backup to condoms, others as a substitute. Many aren't using it at all; some use it on and off, when they are not in a monogamous relationship. Some want to start. At my kitchen table, one writer friend said that having lived through the 1990s, he'll never take the condom off. It'll never — for him — feel safe or sexy.

Me? When my boyfriend read an early draft of this piece, he asked if I wanted to get on PrEP. "No," I said, "I don't. Do you?" Reading this made him feel like HIV is inevitable, especially given the numbers concerning men of color. But this moment we're in makes me feel hopeful. Even if HIV happens, so what? I used to think that HIV would make it harder to find love and sex. Now we know that HIV-positive and undetectable is safe. It's sexy. I have friends who prefer to sleep with undetectable men. They know that most HIV transmission is by people who don't know they're infected or aren't on treatment. For an acquaintance who prefers not to use condoms for his hookups, people who know they're positive and are on drugs are the safest bet.

"Our story is about to change," Dr. Daskalakis told me. He meant the public health programs the city is about to enact. For me, it's true of our cultural moment: a disorienting pivot from everything we told ourselves to be true. The line between HIV-negative and -positive, between bodies safe and not safe to sleep with, is becoming porous.

The political moment we're in only amplifies this feeling. We might go back to 2012 — before Truvada, before we knew that undetectable means safe. We might go back further. I can imagine a future where only people with money can treat or prevent HIV. For many, that's still today's reality anyway, and it probably won't change under the Trump administration. Remember that more than half of the people with HIV aren't on treatment right now.

So yes, we now have good HIV medicine for both treatment and prevention. Pills don't cure us, but they might keep us alive. In 1996, people were so near to death, and then they weren't. Pills do beautiful, beautiful things. Pills can't do it all. Pills can't make us better at negotiating consent or understanding risk. Pills are not healthcare infrastructure in communities that need it. Pills don't erase stigma. Pills exist where people can afford them. Pills exist for people who can get to doctors, clinics, and hospitals.

In New York City, Truvada has become something like mainstream. All living is risky. All sex, too. I've slept with people I didn't love enough when they loved me deeply. I've slept with people I loved who didn't love me enough, who lied, who cheated. I've had joy, too, even with that ex: when we made love as midnight brought in my thirtieth birthday. Joy: the Grindr hookup I had whose body fit mine. Joy: the first kiss with my current boyfriend, a bundle of nerves, leaning forward on my couch, our glasses clinking at the nose. For decades, and still too often, these small moments of pleasure could bring death.

In the past three years, I've been able to imagine a new type of pleasure. Remarkably, this pleasure is one willing to inhabit my own body. I don't know if it's PrEP — even though I don't take it — or the idea that being undetectable is safe, healthy. I don't know if it's because I have a partner I trust with my life, but I suspect it's something more than that.

Even with boyfriends or girlfriends I trusted before, I could never have sex without feeling my life and death were at stake. Now, with my boyfriend, we strip each other naked, no Truvada in either of our blood. In these moments, my mortality is growing smaller and smaller. Sometimes I don’t think about it at all.

November 20, 2015

Remission on HIV


The term remission is increasingly being invoked in the context of cure research and, by extension, is an issue for regulatory authorities such as the U.S. Food and Drug Administration considering measurements of safety and efficacy in clinical trials. Remission, as an outcome, has been applied in a number of cases where people with HIV have interrupted antiretroviral therapy (ART) and maintained low or undetectable viral loads for some period. It is also being assessed as a possible endpoint in a clinical trial (IMPAACT P1115) aiming to test whether starting ART immediately in perinatally infected newborns might later allow for temporary or even long-term treatment interruption.

The hope is that achieving remission will represent a first step toward the discovery of a permanent cure. While this idea may seem relatively straightforward, there are important differences among reported cases in terms of how remission was achieved and significant challenges in assessing whether post-ART control of viral load leads to a state of health equivalent to that of an individual on effective ART or a comparable HIV-negative person.

Current evidence indicates that the examples of possible remission that have been reported recently (see table) fall into two categories. In the widely publicized case of the so-called Mississippi baby, in whom HIV remained undetectable for 27 months after stopping ART, and the two adults known as the Boston patients, HIV appears to have been totally inactive during the period off ART. This was likely because the reservoir of latently infected CD4+ T cells in their bodies was extremely small, lowering the probability of one of the cells becoming activated and awakening the latent HIV within it (CD4+ T cells can activate if they encounter an antigen they recognize or respond to signals from immune system proteins such as cytokines and chemokines). However, the probability was not zero, and it is thought that eventually one or more of the latently infected CD4+ T cells became activated, allowing it to generate new viruses that went on to infect new cells and cause the viral load to rebound. 

Importantly, no immune responses against HIV were detectable in these three individuals until after viral load became detectable, arguing against any role of the immune system in containing the virus during the remission. In the Mississippi child, very early initiation of ART suppressed the virus before HIV-specific immunity developed, whereas in the Boston patients the maintenance of ART during their stem cell transplants (given as treatment for cancer) meant that the new immune system that developed from the donated stem cells did not encounter HIV antigens, so no virus-specific immunity was generated.

A different scenario applies in individuals referred to as post-treatment controllers, who are sometimes described as being in virological remission (the term functional cure has also been used, but is falling out of favor). The most famous examples are the VISCONTI cohort, a group of individuals in France who started ART soon after infection, remained on treatment for several years, then interrupted and maintained viral loads around or below the limit of detection. 

Another instance of virological remission that was in the news recently involves a perinatally infected French teenager in whom ART was interrupted at around age six; with the exception of two low-level detectable readings, viral load has since been maintained below the limit of detection for over 12 years.

A unifying factor that distinguishes these individuals from the Mississippi child and Boston patients is that HIV-specific immunity is present, and while the mechanisms of viral-load control are under investigation, the preponderance of opinion is that immunologic factors are most likely involved (whether adaptive HIV-specific immune responses, innate immune responses, or some combination of both).

Amid these possible examples of remission, the question whether there are implications for long-term health that may differ from those associated with ART-mediated HIV suppression has gone largely unasked. But it is critically important, both for the individuals concerned and for future regulatory assessments of interventions that might promote remission.

There is reason to be optimistic that in cases where HIV is completely inactive, there would be little or no possibility of the virus causing immunologic or health problems. Nevertheless, it would still be desirable to formally evaluate the question in clinical trials, which may be possible if IMPAACT P1115 is successful in recapitulating the remission experienced by the Mississippi child in some participants.

In post-treatment controllers, however, there is already some evidence to suggest that immune-mediated containment of viral load could come at a cost to long-term health. The evidence derives from studies of elite controllers (ECs), who naturally suppress HIV to undetectable levels without ART. While ECs are at a massively reduced risk of disease progression compared with untreated HIV-positive individuals with higher viral loads, it has become evident over long-term follow-up that ECs can experience a slow loss of CD4+ T cells, gradual progression to AIDS, and increases in biomarkers of cardiovascular disease. The driving factor appears to be immune activation, which, on average, is higher among ECs than in comparable HIV-negative individuals. There is also some evidence that ECs may be hospitalized more often than similar HIV-positive individuals on ART, due primarily to cardiovascular disease, but this has been reported in only one study, and it’s possible that confounding factors -- such as smoking -- contributed to the difference.

The potential relevance of these observations to post-treatment controllers is highlighted by a recent update on the VISCONTI cohort at the IAS Towards an HIV Cure Symposium in July. Of the 14 individuals described in the 2013 publication, one has experienced a viral-load rebound reaching close to 100,000 copies/mL after six years off ART, necessitating reinstitution of treatment. Another has a persistently detectable viral load in the range of 100-1,000 copies/mL and a declining CD4+ T-cell count that is now below 500 cells/mm3. A third is reported to have developed a head and neck cancer and has resumed treatment. One of the original 14 is now lost to follow-up. Of the remaining 10 still being followed, nine have viral loads less than 20 copies/mL, while one had a viral-load level of 211 copies/mL at the time of last measurement. The presentation also notes that six post-treatment controllers have been added to the cohort, explaining the reference to a total of 20 members from earlier this year. 
However, data are shown for only one of these individuals, who is controlling viral load but has a CD4+ T-cell count below 400/mm3.

Several important concerns are underscored by this news:
The term virological remission tends to be truncated to just remission, which most people understand to mean a state of freedom from risk of disease. But the immune activity required to contain HIV in post-treatment controllers could be associated with negative health consequences, as has been reported in some ECs. Certainly, media descriptions of the VISCONTI cohort as examples of functional cures (which included a high-profile BBC story) were mistaken, and this term should not be used in relation to post-treatment control.

The widely reported suggestion that the VISCONTI cohort would likely not face the disease progression and health risks reported in some ECs because of lower immune activation should be viewed with skepticism. Immune activation levels in these post-treatment controllers have not been compared with those in HIV-negative individuals, and no data on inflammation levels or biomarkers of cardiovascular disease risk have been presented.

From the regulatory perspective, the benefits and risks of the HIV suppression seen in post-treatment controllers compared with that achieved by ART are currently unknown and will need to be evaluated in randomized studies. There are planned trials of ART interruption in individuals treated very early after HIV infection that may be able to look at this question if a sufficient number of participants display post-treatment control.

Since this may sound pessimistic, it should be noted that research on ECs offers reasons for hope as well as concern. There is evidence from several studies that a subset of ECs maintains extraordinarily strong suppression of HIV and shows immune activation and inflammatory gene expression profiles that closely resemble those of similar HIV-negative counterparts. And at least one reported case suggests that similarly strict control of HIV may be achievable in some post-treatment controllers. A logical implication is that the risk of HIV-related disease progression and illness would be extremely low or absent in these individuals unless levels of virus increase. These findings also imply that gradations in viral-load levels may be important even when the levels are extremely low and undetectable by standard clinical tests.

The refinement of biomarkers of immune activation and inflammation -- which have been associated with both disease progression and morbidity and mortality in population-based studies -- could also aid in the understanding of how low HIV levels may or may not affect health. Currently, there is a great deal of variability in how these biomarkers are measured in different studies, and it would be helpful to achieve consensus about how they should be evaluated in cure-related trials. Early discussions around endpoints in clinical trials where remission or post-treatment control is the goal have focused on standard virological measures (there is a proposed endpoint named virus suppression off therapy, or VSOT), which may not provide sufficient information about the prognosis of an individual who appears to be controlling viral load.


The overall message from recent research is that various forms of remission and post-treatment control are possible, but need to be better understood, particularly in terms of their long-term health implications. While the type of remission observed in the Mississippi baby and Boston patients appears ideal, it is very difficult to achieve because it requires very large reductions in the size of the latent HIV reservoir. The development of reservoir-reducing interventions is a key priority for cure research, and multiple trials of potential candidates are under way, but the task is challenging.
Post-treatment control has been posited as a more realistic goal in the near term, but there is a need to ensure that it leads to a state of health that is at least comparable to that attained on ART, if not better. When encountering terms such as remission, functional cure, and post-treatment control — which all too frequently have been used interchangeably — it's important to appreciate that there remains a lack of consensus as to how exactly to define them, which will hopefully be resolved as the science evolves.

Recent HIV Remission and Post-Treatment Control/Virological Remission Cases*
Period off ART
HIV Detection off ART
HIV-Specific Immunity off ART

ART initiated within 48 hours of birth, interrupted at around age 18 months
27 months
No HIV DNA, RNA, or replication-competent virus detectable in blood
Not detected
Boston patient #1
ART, stem cell transplant, and associated immune suppressants and chemotherapies for cancer
12 weeks
No HIV DNA, RNA, or replication-competent virus detectable in blood or rectal tissue
Not detected
Boston patient #2
ART, stem cell transplant, and associated immune suppressants and chemotherapies for cancer
32 weeks
No HIV DNA, RNA, or replication-competent virus detectable in blood or rectal tissue
Not detected
ART initiated within 100 days of infection and maintained for an average of ~3 years
Average of 9.3 years at the time of last published report (January 2015)
Average HIV DNA levels in blood: ~50 copies/million cells
HIV RNA ranging from <20 copies="" ml="" p="" to="">
HIV-specific antibodies, "robust" HIV-specific CD4+ T-cell responses, low-magnitude HIV-specific CD8+ T-cell responses (not capable of suppressing HIV replication in vitro)
French teenager
Combination ART initiated at 3 months of age, interrupted at around age 6 years of age
>12 years
HIV DNA levels in blood ranging from 125 to 316 copies/million cells
HIV-specific antibodies, low-magnitude HIV-specific CD8+ T-cell responses (not capable of suppressing HIV replication in vitro)
67-year-old European male (Jan van Lunzen case report)
ART initiated within one month of seroconversion, maintained for 5.5 years
>9 years
No HIV DNA or RNA detectable in blood, cerebrospinal fluid, and gut tissue
Replication-competent HIV detected after transfer of CD4+ T cells into humanized mouse
HIV-specific antibodies, strong polyfunctional HIV-specific CD8+ T-cell and CD4+ T-cell responses
23-year-old African female (Sabine Kinloch case)
ART initiated during acute infection, maintained for ~6 years with one switch due to virological failure
>10 years
HIV DNA levels in blood ~150 copies copies/million cells
HIV-specific antibodies, HIV-specific CD4+ T-cell responses and CD8+ T-cell responses (capable of suppressing HIV replication in vitro)
* These are recently reported examples, but several others have been reported in the past, including very rare cases involving individuals treated during chronic HIV infection. See citations included in the cure research section of TAG's 2015 Pipeline Report.

September 16, 2015

“1,2 Punch” Researchers cAn Reawaken HIV then Kill it!



Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a new class of drugs that may be used to purge pockets of dormant HIV from a patient’s body, eliminating the virus once and for all. Fortuitously, these agents are already being explored in clinical trials for treating cancer, which could speed up the route to approval for treating HIV.

Antiretroviral therapies have made it possible for people to live with AIDS for decades. However, small reservoirs of a patient’s cells hide the virus. That is, HIV’s genes live in the cells, but its genetic code is never read to make protein, and so the virus goes undetected by the immune system.

“If you take people off the antiretroviral therapies, some of these dormant cells reawaken to make more virus,” said lead author Lars Pache, Ph.D., a postdoctoral fellow in the lab of Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at SBP. “The key for a cure for HIV is to purge these cells that have dormant HIV.”

Reactivating latent HIV-infected cells so that they can be killed off once and for all is called ‘shock and kill.’ The approach has remained elusive so far, because drugs that reawaken the virus could also trigger massive immune system activation, which itself could be deadly, Chanda said.

The new study, published September 9 in the journal Cell Host & Microbe, “uses a class of drug called Smac mimetics to tap into a cell pathway that can be used to wake up the virus but, based on clinical studies and our data, doesn’t appear to activate the immune system,” Chanda added.

The study started with a broad search of genes within the host cells that help keep the virus silent. Chanda’s group identified 651 genes. They then created batches of cells in which each one of those genes was silenced, and they measured how much HIV the cells produced after they were exposed to the virus.

The scientists whittled the list of candidate genes down to 139, to 24, and then 12 using increasingly stringent criteria. The absence of one gene in particular, BIRC2, boosted the activity of HIV. Even better, Smac mimetics—already proven safe in early-stage clinical trials for cancer—works by inhibiting BIRC2 and related molecules.

“These experiments led us to develop a strategy of using Smac mimetics to reawaken dormant HIV so that we could then kill it with anti-viral therapy,” said Chanda.

Chanda’s colleague at SBP, Nicholas Cosford, Ph.D., professor in the Cell Death and Survival Networks Program, had recently described a potent BIRC2 inhibitor, SBI-0637142. “This drug is about 10-100 times more potent than the small molecules currently in clinic development, making it a promising candidate to tackle HIV latency,” says Chanda.

Part of the reason that HIV’s genes stay hidden in its host is that they cover themselves with tightly wound DNA. A class of drugs called histone deacetylase inhibitors, which unfurls the DNA, is used to treat a variety of conditions. Although most of these inhibitors haven’t worked well on their own to reactivate latent HIV, they might work well with Smac mimetics including SBI-0637142, Chanda’s group reasoned.

The key question was whether they could reactivate the virus in cells from HIV-infected patients undergoing antiretroviral therapy. They combined SBI-0637142 with a histone deacetylase inhibitor (panobinostat) and saw signs that the virus had reawakened without triggering immune cell death.

“We anticipated that we would see a synergy because the drugs work along parallel pathways. What we didn’t expect was the level of activation—the potency and efficacy with which we were able to reverse latency in patient samples,” Chanda said.

They saw similar results in patient cells treated with a combination of LCL161—a Smac mimetic that is already in phase 1 and 2 trials for treating cancer—and panobinostat. “This is a one-two punch for HIV,” said Chanda, adding that ultimately, a cocktail of drugs will be necessary to cure HIV.

The scientists hope to partner with a pharmaceutical company to develop these molecules for testing in animal models of HIV and then move them into the clinic if they meet the safety and efficacy criteria.

In addition to SBP, the study consortium included the University of Utah School of Medicine, The Salk Institute for Biological Studies, the Perelman School of Medicine at the University of Pennsylvania, the Icahn School of Medicine at Mount Sinai, the Paul-Ehrlich-Insitut, and the German Center for Infection Research.

This post was written by Kelly Chi, a freelance science writer. 

July 21, 2015

CUBA 1st Country to Eliminate Mother to Child HIV


Cuba has officially become the first country in the world to eliminate the transmission of HIV and syphilis from mother to child.

Margaret Chan, director-general for the World Health Organisation, described the small Caribbean island’s achievement as: of the greatest public health achievements possible.

Cuba’s success is the first step in a potential victory of the fight against HIV and AIDS. Its milestone is important on several fronts in the global health governance work towards an AIDS-free generation.

It also resonates in the Millennium Development Goals to reduce child mortality, combat HIV/AIDS, malaria and other diseases as well as in the sustainable development goals to reduce the global threat of HIV and AIDS.

What lies behind Cuba’s success

Cuba’s health system is described as being a model for the world, despite a lack of resources and financial assistance. It provides access to health care for its entire population of more than 11 million and provides assistance, including provision of doctors, to other developing nations.

The healthcare system is linked to research and development, providing constant innovation in treatment and care. It is based on preventive medicine, instead of a curative model, which is more costly and less effective.

The main drivers in eliminating mother-to-child transmission were:

* the combined efforts of the Cuban government;
* its political tenacity in working to stop the halt of the virus; and
* the efforts of Pan-American Health Organisation in ensuring Cuba adhered to its programmes to stop the progression of transmission.

Their success story is partly as a result of the Pan American Health Organisation’s access to medicines programme which increases mothers' access to anti-retroviral drugs in the region.

In partnership with the WHO the organisation implemented two strategies: the Global Elimination of Congenital Syphilis strategy and the 2011 Global Plan towards the elimination of new HIV infections among mothers and children.

These effectively increased governments' political will to engage with HIV-positive citizens.

These regional initiatives controlled the spread of the disease. It showed success and consistency in their approach to stem risky behaviour which could increase transmission.

Within the country there were three major drivers that broke the infection chain for transmission. A decision was taken to provide additional HIV and syphilis testing for pregnant women and their partners; women were offered caesarean deliveries instead of natural deliveries; and breastfeeding was substituted.

Cuba also initiated a nationwide HIV screening program during 1985 and 1986. HIV screening is still required for expectant mothers. Voluntary screening is also encouraged. As a result, over 23 million HIV tests have been performed. HIV-positive females receive AZT as a matter of priority from 14 weeks of gestation.

The global picture

Each year about 1.4 million infected women across the globe fall pregnant. Without anti-retrovirals, these women have a 15% to 45% risk rate of transmitting HIV, either during pregnancy, labour or breastfeeding. If anti-retrovirals are provided, the risk drops to 1% of transmission.

Currently seven of the 10 pregnant women across the globe have access to anti-retrovirals to prevent viral transmission. This is an increase in access to anti-retroviral medication in low and middle income countries and should result in increased prevention of transmission of the virus.

Of the 22 countries which account for 90% of the new HIV infections, eight have reduced new infections by more than 50% since 2009, with an additional four creeping closer towards this milestone.

Lessons southern Africa can learn

What Cuba’s success story means is two-fold. First, it is possible to eliminate mother to child transmissions, within measure. Second, the intervention and assistance of a regional organisation is effective in reducing transmission and providing access to anti-retrovirals.

Southern Africa, which has the highest rate of HIV/AIDS in the world, should take heed. The spread of the disease remains at the forefront of the development agenda for the heads of state in the Southern African Development Community or SADC.

If the SADC could mimic or adopt the same level of success that the Pan American Health Organisation has, this could significantly decrease mother to child transmission in the region.

The SADC secretariat should facilitate and co-ordinate regional issues and health care. But it is only mandated to assist with policy making that is approved by member states.

The secretariat has a HIV and AIDS unit, which assisted with a strategic framework. And most member states have adopted national policies or strategic development plans to address the country specific problems.

But co-ordination of policy is only executed once the SADC member states agree to implement the policy. A separate plan, the Pharmaceutical Business Plan, which was developed to address the need for regional provision and management of medication, has not been renewed.

Despite significant policy attention and the development of a regional cross border HIV and AIDS initiative, it remains to be seen how the region will fare in its struggle to reduce the epidemic.

Efforts to increase access to anti-retrovirals are continually hampered with problems of stock outs, limited political will and logistical difficulties. South Africa and Zambia, two prominent countries in the region, have experienced medication stock-outs. The need for a strengthened regional presence is evident.

This article was originally published on The Conversation by 

HIV in Remission for over 11 Years

A French teenager’s HIV infection is still in remission more than 11 years after her medications were discontinued, the longest hiatus on record for a young person and the best indication yet that long-term interruption of the infection is possible in children, a researcher revealed Monday.
The virus has been undetectable in the teenager’s blood since she was 21 months old, according to the information presented Monday at the 2015 International AIDS Society conference in Vancouver. She is now more than 18 years old and has not received anti-HIV medication since she was almost 6 years old. A blood test shortly before her seventh birthday showed no presence of the virus.
Asier Saez-Cirion, an assistant professor at the Pasteur Institute in Paris who conducted the research, was quick to note that the unidentified teen is not cured of HIV infection and that experts are not sure what caused her lengthy remission. With sophisticated tests, they can detect biological evidence of the virus in her blood, though not the virus itself.  
“This girl is in remission,” Saez-Cirion said in an interview. “She’s not cured.”

Nevertheless, the case presents a number of possibilities for researchers seeking further progress against HIV, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
“There’s no measurable immunological reason why the [teen] is controlling” the virus, Fauci said. “But the [teen] is obviously controlling it.” 
In 2013, doctors reported that they had achieved a “functional cure” for the HIV infection in a Mississippi girl who was put on anti-retroviral therapy within hours of her birth. But in July 2014 — 27 months after her aggressive treatment ended — her doctors announced that she had tested positive for HIV, a setback for researchers seeking to cure a disease that affects 35 million people around the world.
Another child in Italy who was thought to have been cured in 2014 relapsed after two weeks off the medication. A very small number of adults infected with HIV have been known to live many years without detectable levels of the virus in their blood despite ceasing treatment. Known as “elite controllers,” they have been studied in an effort to determine how they naturally keep their viral loads in check. In children, such a response is even more rare than among adults.
Steven Deeks, a professor of medicine at the University of California, San Francisco, said further research must confirm that the remission is real, rule out the possibility that the teen is an elite controller, determine the mechanism of control and try to predict who might benefit from the same approach. 
“The real question here in the teenager is whether this is truly novel or whether this teenager would have controlled her virus anyway, the way others have in the past,” Deeks said.
Like the Mississippi child, the French teen was treated aggressively with anti-retroviral medication shortly after she was born to an HIV-infected mother whose illness was not controlled. It is uncommon to start drug therapy in a newborn before the virus is detected, but cases like these two may change that approach, Saez-Cirion said. 
In this case, the girl was given the drug zidovudine as a preventive measure for six weeks after birth, when treatment was suspended. The virus was first detected in her blood at the age of four weeks, and her viral load peaked at three months, when she began receiving a regimen of four drugs.
A month later, the virus was undetectable and remained that way except for two occasions, when she was tested at 15 months and 21 months of age. Shortly before she turned 6, her family discontinued the combination therapy. A year later, she was tested again, and no virus was detected in her blood. A decision was made not to resume the medication. 

 As yet, there are only theories about the lengthy remission. Saez-Cirion noted the interruption in the girl’s treatment between six weeks and three months of age. Perhaps that allowed her to develop some kind of immunity, Saez-Cirion said. 
“It means that for a few weeks, this girl was in contact with the virus, which may have been helping the immune system to combat the virus,” he said.
But if that’s true, Fauci noted, evidence of an immune response is not showing up in her blood tests. “That’s possible,” he said, “but they can’t measure it.”
Fauci pointed out that the child’s combination treatment began at three months “during what would be the functional equivalent of an acute infection,” when her viral load was very high. He wondered whether that timing helped her develop protection from the virus.
Saez-Cirion said he learned of the teen’s case after following the announcement of the Mississippi child’s remission. In recent months, his researchers have been running tests on the young woman to learn what they could about the teen’s condition before making news of her case public.
There is no way to predict the length of the teen’s remission, Saez-Cirion said. She very well may live a normal life span, he said, but as she ages, her immune system is likely to weaken, as most people’s do.
“We are not sure how long this may last,” he said. “Once people have been in remission for a couple of years, chances...are going to be higher.”

Lenny Bernstein Lenny Bernstein writes the To Your Health blog. He started as an editor on the Post’s National Desk in 2000 and has worked in Metro and Sports.
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