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Five lessons from CROI 2015
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The value of pre-exposure prophylaxis, or PrEP, in HIV-negative individuals at risk for infection was one of the hottest topics at CROI 2015, according to Joel Gallant, MD, MPH, immediate past chair of the HIV Medicine Association, medical director of specialty services at Southwest CARE Center in Santa Fe, New Mexico, and board member of the International Antiviral Society-USA.
Infectious Disease News spoke with Gallant about five important lessons learned at this year’s conference on the prevention of HIV and the future clinical implications of some of the major studies that were presented.
PrEP is effective, with minimal drug resistance
The Pragmatic Open-Label Randomized Trial of Pre-Exposure Prophylaxis (PROUD) study found that a PrEP regimen consisting of Truvada (tenofovir/emtricitabine [TDF/FTC]; Gilead Sciences) provides significant protection against HIV, surpassing the levels of protection previously noted in placebo-controlled trials. In the study, 545 high-risk men who have sex with men (MSM) were randomly assigned to receive open-label daily TDF/FTC either immediately or after a 12-month deferral. Three HIV infections occurred in the group receiving immediate PrEP vs. 19 in the deferred group, an 86% reduction.
Joel Gallant
Additionally, the PROUD study found that while three patients developed resistance to the drug FTC, none became resistant to TDF.
“They found little drug resistance and no evidence of higher risk behavior among PrEP takers, undermining two of the commonly voiced arguments against PrEP,” Gallant said.
‘On-demand’ PrEP may be successful approach to prevention
The ANRS Ipergay trial found that among MSM, an “on-demand” PrEP regimen of TDF/FTC — in which two pills were taken prior to each sexual encounter and one pill taken 24 and 48 hours after the first dose — was highly effective in preventing HIV infection.
“One remaining question is whether we can now recommend on-demand as opposed to continuous PrEP based on Ipergay,” Gallant said. “We know from the iPrEX OLE study that taking as few as four tablets of Truvada per week may be enough to prevent infection. The median number of pills being taken by Ipergay participants (16 per month) was close to that, which raises the question of whether this was really just near-continuous PrEP. On the other hand, half the patients were taking less than 16 pills per month, and the efficacy was still very high. It will be interesting to see whether this unapproved way to use PrEP will be embraced by the community.”
PrEP can serve as a ‘bridge’ to ART in serodiscordant couples
The Partners Demonstration Project found that among serodiscordant couples to whom PrEP was offered as a “bridge” until the infected partner had been on ART for at least 6 months, 95% of couples started PrEP at enrollment and 97% were still using PrEP at their 1-month follow-up. This was an uncontrolled trial, and the researchers compared observed transmission rates with what would have been expected based on historical data. Only two transmissions occurred, compared with the 40 that were expected, for a 96% reduction in transmission. Neither of the participants who seroconverted had detectable tenofovir levels in plasma.
“I’m often asked whether HIV-negative partners in serodiscordant couples should use PrEP,” Gallant said. “If the couple is monogamous and the positive partner has a consistently undetectable viral load, I generally advise against it. But using ‘PrEP as a bridge to ART’ is a strategy that has always made a lot of sense. Now we have a study to support this approach.”
The link between abacavir and MI is still not fully understood
Another important study presented at CROI 2015, according to Gallant, was an analysis of the association between abacavir and myocardial infarction (MI) in the large North American HIV cohort study, NA-ACCORD. The analysis of 16,733 adult HIV patients found that recent abacavir use was associated with an increased risk for MI. However, the risk was attenuated after adjusting for traditional and HIV-associated risk factors, and in one of the three models presented, the association failed to achieve statistical significance. Additional analyses from this cohort are now are under way to adjust for potential time-dependent confounders of MI risk.
While some previous observational studies have shown an increased risk for MI among abacavir patients, others have shown no increased risk, and the association remains controversial.
“The long-awaited NA-ACCORD analysis was important, not because it answered the question and resolved the controversy, as we had hoped it would, but because its somewhat confusing and non-definitive results have kept the controversy alive,” Gallant said.
Tenofovir alafenamide appears to be a safer formulation of tenofovir.
Gallant noted several presentations at CROI 2015 that focused on the efficacy and safety of tenofovir alafenamide (TAF) compared with tenofovir DF (TDF), the version in use today.
“The various presentations on TAF show it is as effective as TDF and appears to be living up to its promise as a safer form of tenofovir, with minimal kidney and bone toxicity,” Gallant said. “We expect to see a number of TAF-containing coformulations approved later this year and early next year, and if pricing is favorable, it’s conceivable that it could quickly become the preferred form of tenofovir.” – by Jen Byrne
Disclosure: Gallant reports that his institution receives grant support from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck, Sangamo BioSciences and ViiV Healthcare. He is an advisor or consultant to Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck and ViiV Healthcare.