Maraviroc Looks to be Safe For Use as PrEP, But is it Effective?


Maraviroc’s safety profile makes it a potential drug of choice for those at risk of contracting HIV, but a recent study raises questions about how well it works.

Ian McGowan, MD, PhD, FRCP, a professor of medicine in the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh School of Medicine

Drugs used to treat or prevent HIV, while effective, often result in substantial side effects. An example is the tenofovir disoproxil fumarate/emtricitabine combination, sold as the pre-exposure prophylaxis (PrEP) product Truvada. Although Truvada prevents the transmission of HIV through sexual contact by a rate of more than 90%, studies have found that it can affect kidney function and reduce bone density, making it a poor choice for some individuals. Another antiviral drug, maraviroc, has a superior safety profile but has not been shown to be effective against a wide variety of HIV infections. For this reason, investigators are interested in whether maraviroc might be put to better use for the prevention rather than treatment of HIV.

A study sponsored by the US National Institutes of Health’s Division of AIDS and conducted by investigators at the University of Pittsburgh Medical School, Weill Cornell Medicine in New York, and other locations aimed to learn whether maraviroc is an effective choice for use as a PrEP medication.

The team enrolled 406 at-risk men and transgender women, none of whom had HIV. The participants were randomized to receive 1 of 4 different drug regimens used in PrEP, including maraviroc by itself, maraviroc plus emtricitabine, maraviroc plus tenofovir disoproxil fumarate, and tenofovir disoproxil fumarate plus emtricitabine. The subjects were then followed for 48 weeks, with blood and rectal fluid samples drawn at intervals.

Out of this study, 59 participants—all men who have sex with men—were enrolled in a smaller study that involved providing rectal tissue biopsy samples. These tissue explants were exposed to HIV and then challenged with 1 of the 4 PrEP drug regimens used in the larger study to determine whether there was measurable viral suppression in an in vitro setting.

One question the investigators had was whether maraviroc is associated with increased T-cell activity in HIV-negative people, which could disqualify it for use in PrEP. The answer turned out to be no.

“We know that activated T-cells are more vulnerable to HIV infection than nonactivated cells,” Ian McGowan, MD, PhD, FRCP, a professor of medicine in the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh School of Medicine and an author of the study, told Contagion®. “Any product that might increase activation might increase the in vivo risk of HIV infection. A key finding from our study was that maraviroc did not seem to increase T-cell activation.”

Although this lack of T-cell activity means that maraviroc might be safe for use as a PrEP agent, the investigators are not yet sure it would be effective. This is because the maraviroc-alone arm of the tissue substudy led to little or no viral suppression from the baseline measurement at the beginning of the study to week 48, while the other 3 combination arms did display viral suppression.

“The tissue explant data could suggest that maraviroc is not a good choice for a PrEP agent or that the explant model is not a good model to evaluate maraviroc as a PrEP agent,” Dr. McGowan said. Citing another study that showed maraviroc rapidly dissipating from explant tissue as well as his team’s own unpublished data, he added, “I think that the second explanation may be more relevant to our study.”

Five participants contracted HIV during the course of the study, 4 of whom were randomized to the maraviroc-only arm; however, Dr. McGowan claimed that based on the study design, this finding was not statistically significant. “We have … shown that maraviroc does not seem to be active in reducing HIV infection in this explant system, and it remains to be seen whether this translates to poorer efficacy in clinical efficacy trials,” he said. “The only way to determine whether maraviroc alone or in combination with other PrEP agents is better than Truvada would be a fully powered head-to-head comparison.”

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