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Maraviroc May Need Help as PrEP

Maraviroc

The findingspresented at this year’s Conference on Retroviruses and Opportunistic Infections were less positive than hoped. The NEXT-PrEP study, examined the possibility of using the drug Maraviroc as an alternative to Truvada as a method for pre-exposure prophylaxis to prevent HIV.

Maraviroc had been considered a particularly viable candidate for PrEP because, it’s a type of drug not commonly used in treating HIV. That uniqueness lowers the chance of someone becoming resistant to the drug; and could make it an alternative for those who’ve developed Truvada-resistance.

An entry inhibitor, Maraviroc prevents HIV infection by attaching itself to the same part of the white blood cells that the virus needs to connect with, thus blocking HIV from attaching and replicating.

Dr. Roy Gulick of Cornell University and his team administered Maraviroc alone and in conjunction with tenofovir or emtricitabine to 399 gay and bisexual men and 7 trans women. To be included in the study the participants (who ranged in age from 18 to 70) had to have reported unprotected anal sex with a person of positive or unknown HIV status in the previous three months.

Over the course of the 48-week study, five HIV infections occurred: four among participants with low/undetectable levels of Maraviroc in their bloodstreams, indicating poor adherence to the regimen. As with Truvada, adherence would remain an important element in achieving the greatest protection from HIV with a Maraviroc-based PrEP.

The final participant who contracted HIV had detectable but erratic levels of Maraviroc in bloodwork. Statistically a single failure doesn’t detract from Maraviroc’s effectiveness in preventing HIV; but another report just might.

In a separate CROI presentation, Ian McGowan of Pittsburgh University acknowledged that Maraviroc hasn’t performed as well as hoped as a PrEP regimen in previous animal and human studies. A topical vaginal microbicide showed promise in monkeys, but not in humans; an oral pill and previous single-dose option had also been disappointing.  

To understand what might be happening, McGowan conducted studies using explants —  samples of rectal tissue from biopsies given by NEXT-PrEP study participants — that were cultured with HIV in the lab to see if they became infected.

He found ten times the level of HIV proteins in cells that had only been treated with solo Maraviroc rather than treated with Maraviroc combined with tenofovir or emtricitabine.

McGowan believes that the cause is solo Maraviroc “disassociating” or separating from the receptors in the explant cells. Because Maraviroc works by blocking HIV, once the drug detaches from the receptor, HIV can take its place, attaching and infecting the cell.

Still unknown is whether this disassociation only occurs in the lab versus in real life. As it is, Maraviroc has been shown to be effective when taken in conjunction with either tenofovir or emtricitabine.  

Gulick projected that the combo of Maraviroc and emtricitabine could be a PrEP alternative for individuals with pre-existing kidney troubles. As AIDSMap reported last month, Truvada has been linked with modest kidney function decline, so people with pre-existing issues could be in the market for another PrEP option.

However, Gulick didn’t report on NEXT-PrEP participants’ kidney function and a bone density report is also pending. Further studies will need to be conducted, to determine the most effective drug combination(s) and whether disassociation is a real world problem.

 

Tags: Prevention, PrEP

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