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Confab discusses HIV research news

by Liz Highleyman

Dr. Joseph Eron spoke about new research at IAS 2017.<br>Photo: Liz Highleyman
Dr. Joseph Eron spoke about new research at IAS 2017.
Photo: Liz Highleyman  

Researchers presented the latest findings on HIV treatment and prevention at the International AIDS Society Conference on HIV Science, which took place in Paris in late July. The most prominent news included advances in long-acting antiretrovirals for both treatment and prevention, and viral remission after stopping treatment.

"Long-acting treatment really is the wave of the future, and it's incredibly gratifying and exciting that the first combination out of the gate seems to be so effective and tolerable," David Evans of Project Inform told the Bay Area Reporter. "I'm really thrilled â€" and I believe many people living with HIV will feel that way too â€" that a combination like this is likely to be a new option in the near future."

Dr. Joseph Eron from the University of North Carolina at Chapel Hill presented the latest findings from a clinical trial evaluating injectable cabotegravir and rilpivirine administered once monthly or every other month for HIV treatment. Cabotegravir is an investigational integrase inhibitor and rilpivirine is a non-nucleoside already approved as an oral medication (Edurant).

This phase 2 study enrolled over 300 people who were starting HIV treatment for the first time. They initially started a three-drug oral regimen, and after 20 weeks those with undetectable viral load were randomly assigned to either stay on the same regimen or switch to cabotegravir and rilpivirine injections given every four or eight weeks.

After two years on treatment, 94 percent of people taking the injectable combo every eight weeks and 87 percent of those taking it every four weeks still had undetectable viral load, as did 84 percent of those who stayed on the oral regimen, Eron reported.

Injectable cabotegravir and rilpivirine were generally safe and well tolerated, and few people stopped treatment early due to adverse events. Injection site reactions were common but mostly mild. Study participants said that they were satisfied with the long-acting therapy and would like to continue on it.

Once-monthly dosing resulted in a slightly lower rate of viral rebound at one year, so this regimen was chosen for phase 3 studies. But Eron said that the every-other-month schedule looked equally effective with longer-term follow-up, and this regimen will also be evaluated in larger trials.

Long-acting injectable cabotegravir is also being studied for HIV prevention. Dr. Raphael Landovitz from UCLA presented the first findings from HPTN 077, a phase 2 study designed to evaluate the safety and acceptability of injectable cabotegravir for PrEP, but not yet looking at its effectiveness.

Cabotegravir injections given every two months produced high enough drugs levels in both men and women to offer protection against HIV, although a larger dose given every three months did not reach this threshold.

Further back in the pipeline, a novel oral drug that could potentially be taken once weekly showed good activity in an early treatment trial. MK-8591, also known as EFdA, is the first nucleoside reverse transcriptase translocation inhibitor.

Dr. Randolph Matthews from Merck presented findings from a small phase 1 study of the antiviral activity of single doses of MK-8591 over seven to ten days in people who had not yet started HIV treatment.

MK-8591 produced "rapid and robust" viral load reductions across a range of tested doses, the researchers reported, with viral load declines exceeding 1 log seven days after administration. Treatment was generally well tolerated with no serious side effects.

Pre-clinical studies showed that MK-8591 had good distribution to rectal and vaginal tissues in monkeys, indicating potential suitability for PrEP.

Dr. Martin Markowitz from the Aaron Diamond AIDS Research Center in New York presented results from a study asking whether MK-8591 could protect monkeys from rectal infection with a simian-human hybrid virus known as SHIV.

Sixteen male macaques were given weekly oral doses of MK-8519 and rectally exposed to SHIV every week. None of the monkeys treated with MK-8591 became infected over the course of 12 viral exposures, while every monkey in the placebo group became infected, mostly after just one or two exposures.


HIV remission

Another big story coming out of the conference was the news that a 9-year-old child in South Africa who started antiretroviral therapy (ART) as a baby has maintained viral suppression off treatment for eight and a half years.

The girl was diagnosed with HIV at the age of one month and received antiretrovirals for just under a year in the CHER trial, sponsored by the U.S. National Institutes of Allergy and Infectious Diseases. Her viral load went from a high level to undetectable and stayed there. An extensive evaluation at age nine showed that she had evidence of HIV genetic material in a small number of immune cells, but no signs of replication-capable virus.

"[T]his new case strengthens our hope that by treating HIV-infected children for a brief period beginning in infancy, we may be able to spare them the burden of lifelong therapy and the health consequences of long-term immune activation typically associated with HIV disease," NIAID director Dr. Anthony Fauci said in a statement.

Dr. Timothy Henrich from UCSF reported on another case of long-term remission involving a gay man who started HIV treatment during the "hyperacute," or very early, phase of infection.

The man joined a PrEP trial and started taking Truvada (tenofovir/emtricitabine), but it was soon learned that he had been infected very recently, before starting PrEP. He then switched to a complete multidrug antiretroviral regimen.

After nearly three years on treatment he showed no evidence of HIV anywhere in his body using the most sensitive tests, and he opted to try a carefully monitored experimental treatment interruption. He maintained an undetectable viral load for about seven months, but ultimately experienced viral rebound and restarted treatment.

"From a cure perspective, the biggest story at the conference was proof that very early antiretroviral therapy is not curative, but that early ART â€" but perhaps not too early â€" can lead to a remission in some people," Dr. Steven Deeks of UCSF, who was one the investigators on this study, told the B.A.R.




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