Taking pre-exposure prophylaxis (PrEP) "on demand," meaning only around the time of sexual intercourse was effective in preventing HIV infection among men who have sex with men (MSM), Jean-Michel Molina, M.D., of the University of Paris Diderot reported at AIDS 2016. Molina presented the final results from an open-label extension of the IPERGAY trial, which had been stopped early because the study regimen overwhelmingly prevented the acquisition of HIV.
The original IPERGAY trial reduced the likelihood of becoming infected with HIV by 86%. Its placebo arm was discontinued early to allow those participants also to benefit from the study findings. However, the high efficacy shown may have been due to initially high adherence rates, Molina cautioned. The shorter duration of the original study also meant that no long-term safety data on the intermittent use of tenofovir disproxil fumarate/emtricitabine (Truvada, TDF/FTC) for PrEP could be gathered.
An open-label extension in which everyone would receive the study drug had been planned before the initial trial was discontinued. The study team was therefore able implement that extension within eight days of stopping the IPERGAY trial. Same as the PrEP arm of the initial study, extension participants took two tablets of TDF/FTC two to 24 hours before having sex and one tablet both 24 and 48 hours after the initial dose. During ongoing sexual activity, participants took one tablet per day and the two final tablets after their last sexual intercourse.
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Everyone enrolled in the original trial who had remained HIV uninfected was invited to join the open-label extension, as were an additional 29 people, resulting in 362 enrollees. Of these, 299 (83%) completed follow up by June 30, 2016. Participants were relatively young (median age 35), overwhelmingly white (93%) and more than one-third (43%) had used psychoactive drugs during the prior 12 months -- a practice Molina called "chemsex." On average, study participants had sex 9.5 times involving seven partners during the four weeks preceding the study survey.
Despite participants' relatively high likelihood of acquiring HIV, only one person seroconverted during the extension trial. This man thought his partner was not living with HIV and therefore did not take PrEP. Testing revealed that his virus had not mutated to become drug resistant. Overall HIV incidence in the open-label extension study dropped to 0.19 per 100 person-years from 6.60 in the placebo arm of the original study and 0.91 in the TDF/FTC arm of the original IPERGAY trial.
At the time of the study, TDF/FTC was not approved for PrEP in France, Molina explained. As a result, the average of 18 pills/month used may be too high because some volunteers probably kept the medication for future use rather than return all pills not taken in a given month.
Based on study surveys, more participants took TDF/FTC during the extension phase than during the original study. Even so, 26% reported not using PrEP before the last sexual act prior to completing the survey. When the levels of the study drug were measured in volunteers' blood, slightly more people had taken at least one pill during the week preceding the blood draw than had in the original study (71% in the extension versus 69% in the original study).
All study volunteers were counseled by peer educators about HIV prevention in general and condom use in particular. The number of sexual acts or partners did not significantly change between the two study periods; however, more participants in the open-label extension engaged in condomless sex during their last receptive anal intercourse than did in the original study. Low condom use was also evident from the higher rate of study participants who acquired a sexually transmitted infection (STI) during the study period. The STI incidence rate of 35.2 per 100 person-years in the original study rose to 40.6 per 100 person-years during the open-label extension phase.
The median follow-up time in the extension trial was about twice that of the original study, yielding safety and tolerability data on long-term intermittent use of oral PrEP. The regimen was generally well tolerated, with mostly mild side effects, mainly related to gastrointestinal problems. Three volunteers dropped out of the study due to low creatinine clearance levels; however, these levels resolved on their own. Seven people in the extension trial showed abnormal alanine transaminase levels, but most of them also suffered from acute hepatitis C infection.
Partly because of this trial, PrEP has since been approved in France and is fully reimbursed by the health care system there. It has also been recommended in the United Kingdom and the European Union and will be approved soon in Canada, according to Molina. While the study data are promising for HIV prevention, the high rates of STIs found in the trial need to be addressed, he concluded.
[CORRECTION 8/15: An earlier version of this article incorrectly stated that TDF/FTC was taken 24 and 48 hours after having sex. We have corrected the text to reflect that TDF/FTC was taken 24 and 48 hours after the initial dose taken prior to having sex.