Sheena McCormack presenting the PROUD study results at CROI 2015. Photo by Liz Highleyman, hivandhepatitis.com.
The most exciting news from CROI concerns pre-exposure prophylaxis (PrEP), the use by HIV-negative people of antiretrovirals to prevent HIV infection.
Two studies of PrEP in gay men and trans women have demonstrated that the availability of PrEP reduced the rate of infection by 86%. This amounts to the highest effectiveness yet seen for PrEP and is superior to most other HIV prevention interventions. Extraordinarily, two separate studies which provided PrEP in very different ways found exactly the same level of effectiveness.
The PROUD study was conducted in England and the IPERGAY study in France and Canada. Both recruited men who have sex with men and trans women who were at elevated risk of acquiring HIV – they had multiple partners, condom use was inconsistent or irregular, rates of sexually transmitted infections (STIs) were high, many participants had needed post-exposure prophylaxis (PEP) before and recreational drug use was common. Participants were generally well-educated and in full-time employment.
Both studies were also designed to be pilot studies, in preparation for larger trials. The fact that each study has demonstrated such a high and statistically significant level of efficacy with a few hundred participants tells us both about how effective PrEP is and how high the rate of infection is in some groups of gay men in western countries.
But there were important differences between the studies.
The PROUD study in England asked participants to take a pill every day (containing tenofovir and emtricitabine, Truvada). Participants randomised to the control group did not receive a placebo, but knew that they would receive the pills after a one-year delay.
Jean-Michel Molina presenting the IPERGAY study results at CROI 2015. Photo by Liz Highleyman, hivandhepatitis.com.
The IPERGAY study tested – for the first time – the idea of ‘intermittent’ PrEP. Participants were told that they only needed to take the pill before and after sex – a dose in the 24 hours before anticipated sex, and then, if sex happened, two separate doses in each of the two days that followed. This approach may make adherence easier, reduce the cost of the intervention and limit side-effects. The pill used was also Truvada and those randomised to the control group received a placebo.
In the PROUD study, the rate of new HIV infections was 1.3% per year in the PrEP group and 8.9% in the control group. The difference between the two figures translates to an effectiveness of 86%.
In IPERGAY, the rate was 0.9% in the PrEP group and 6.8% in the control group, with the difference again translating to an effectiveness of 86%.
Between the two studies, five individuals randomised to receive PrEP acquired HIV. However, none were thought to be taking the tablets at the time – four had stopped attending appointments or were returning unused pill bottles to the clinic. The fifth person is thought to have acquired HIV just before beginning PrEP.
Results are generally reassuring in terms of side-effects, drug resistance and sexual behaviour change.
Adherence proved to be very good in both studies, despite their very different dosing schedules. The PROUD study aimed to replicate ‘real-life’ clinic conditions in England and showed that fears of poor adherence in this setting were unfounded. The IPERGAY results show that gay men are capable of taking PrEP in a way that suits their lifestyle and maximises their safety.