Little by Little Scientist Have Been Gaining Ground on HIV/AIDS~Let Me Tell You~

By Donald G. McNeil Jr.

The New York Times

The unnamed “London patient” —the second person apparently cured of H.I.V. — earned all the headlines. But other research released this week at the Conference on Retroviruses and Opportunistic Infections showed that scientists are making slow but steady progress on the tactics and medicines needed to fight the epidemic, especially in Africa.

Monthly injections of long-acting H.I.V. drugs proved as good as daily pills at suppressing the virus, according to two trials involving more than 1,000 patients. In another study, Descovy, a new formulation of the H.I.V. treatment Truvada, proved just as effective at suppressing the virus and may have fewer — or at least different — side effects.

                                

A study of the “test and treat” strategy in one million people in South Africa and Zambia — the largest H.I.V. prevention study ever conducted — produced mixed results.

Offering widespread home testing plus treatment to the sickest patients did reduce the number of new infections. But offering immediate treatment to all did not help as much as had been expected. 

And a study of pregnant women in Uganda and South Africa showed that a relatively new drug, dolutegravir, was better than the standard treatment for women about to give birth.

The results of those trials were revealed at the C.R.O.I. meeting in Seattle, a scientific conference held each year in the United States. It tends to offer more research and fewer theatrics than the International AIDS Society conferences that move to new cities around the globe every two years.

Proving that injectable H.I.V. drugs work is important because many people forget to take their daily pills or cannot keep pills in their homes.

The success of the two injectable-drug studies — named Atlas and Flair — raised hopes among H.I.V. experts that these shots may eventually be used to protect the uninfected. (Trials testing that idea are underway now, but results are not expected for about three years.)

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Doctors working in poor countries are eager for injections or implants that will release small daily doses of antiretroviral drugs because the devices can be used in secrecy. Providing injections may be harder than handing out pills, but the option may attract patients with H.I.V. who would otherwise stay away.

A study of pregnant women in Uganda and South Africa found dolutegravir to be more effective in fighting H.I.V. than the standard treatment. 

A study of pregnant women in Uganda and South Africa found dolutegravir to be more effective in fighting H.I.V. than the standard treatment.CreditBaz Ratner/Reuters

African women often say they cannot be caught with pills, microbicides, vaginal rings or other anti-H.I.V. measures because they fear that their husbands, lovers, family members or neighbors will mistakenly assume they are infected.

Long-lasting contraceptive injections like Depo-Provera are much more popular in Africa than in the United States because many women must conceal birth control from their partners, who may get angry that they do not want more children.

Similarly, many gay or bisexual men would welcome a discreet way to take H.I.V. drugs because they are hiding from their spouses or families that they have sex with men.

Both studies tested monthly injections of cabotegravir and rilpivirine deep into the buttocks. The shots worked, and only a handful of participants dropped out complaining they were too painful. Post-trial surveys found that 98 percent of the subjects preferred injections to pills.

In poor countries, cabotegravir may be especially useful because it does not need to be refrigerated.

The clinical trial involving Descovy, a new pill from Gilead Sciences containing a form of tenofovir known as TAF — instead of TDF, the form in Truvada — showed that it suppressed the virus just as well as Truvada did.

People who take Truvada every day as PrEP, or pre-exposure prophylaxis, are almost 100 percent protected against getting H.I.V., whether from unprotected sex or drug injection.

The trial, known as Discover, found that Descovy was slightly less likely than Truvada to harm kidneys or bone density, but other studies have suggested that Descovy is more likely to raise cholesterol.

Gilead said it will soon ask the Food and Drug Administration to let it market Descovy as PrEP. Some AIDS activists worry that people at risk will be urged to switch to Descovy just as low-cost generic versions of Truvada become available.

Truvada has been very safe for most patients, but its high price — now about $20,000 a year — and the red tape needed to help the uninsured pay for it have become major obstacles to ending the AIDS epidemic in the United States.

Gilead has already sold $33 billion worth of tenofovir; it is now shifting its new H.I.V. drug cocktails to TAF, which will remain patented — and, presumably, expensive — for many more years.

The trial in 21 neighborhoods in Zambia and South Africa — a region where H.I.V. infection rates are the world’s highest — was designed to see whether infection rates could be dramatically cut if teams of counselors went door-to-door, testing anyone who agreed and offering pills to anyone testing positive. Counselors also offered advice, condoms, circumcisions, tuberculosis tests and other incentives to lower infection rates during the trial, which is known as PopArt and ran from 2013 to 2018.

It was assumed that communities, where patients were offered treatment immediately, would have by far the lowest rates of new infection. But they did not, even though tests suggested that more people there were taking their pills; further analysis of that quandary will be done, the investigators said.

“PopArt is a head-scratcher,” Mitchell J. Warren, executive director of A.V.A.C., an advocacy group for H.I.V. prevention, said in an email. 

Combining the results of the two main subgroups — those offered pills immediately and those offered pills only when they showed early signs of illness — showed that these strategies lowered new infections by about 20 percent.

Therefore, Mr. Warren said, offering treatment without offering PrEP at the same time “is not the way to epidemic control. Frustrating!”

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The pregnancy trial, called Dolphin-2, showed that 74 percent of women who got dolutegravir-based drug cocktails in their third trimester had no H.I.V. in their blood when they gave birth. Only 43 percent of the women who got older efavirenz-based combinations reached that benchmark.

That was a “highly significant” difference in how fast each drug drove the virus out of the blood, said Dr. Saye Khoo, an H.I.V. specialist at the University of Liverpool who led the trial.

That is important because many women in Africa find out they are infected late in pregnancy, and it can be hard to prevent them from infecting their babies.

Some babies in each test group died, and a few were born infected anyway. The investigators believed the deaths were from unrelated causes like sepsis or pneumonia, and that the rare H.I.V. infections occurred early in the pregnancies before either drug regimen could kick in.

Donald G. McNeil Jr. is a science reporter covering epidemics and diseases of the world’s poor. He joined The Times in 1976 and has reported from 60 countries.

Don't be shy with questions!~~~~~~~