Wednesday 29 June, 2016 13.00 EDT
19 March 2015
“On-demand” PrEP strategy highly effective for gay men who have frequent sex
Preliminary results from two exciting PrEP studies – known as PROUD and IPERGAY – were recently presented at the Conference on Retroviruses and Opportunistic Infections (CROI) held in Seattle in February 2015.
In a previous CATIE News, the results of the PROUD study were reviewed. The PROUD study was a real-world study investigating the daily use of Truvada (a fixed-dose formulation of two anti-HIV drugs, tenofovir + FTC) as PrEP. In PROUD, no placebo was used and the study participants knew the pill they were taking was Truvada.
This CATIE News story discusses the IPERGAY results. IPERGAY was different from PROUD as it investigated an “on-demand,” event-driven PrEP strategy and a placebo was used. In the IPERGAY study, participants did not know whether they were taking Truvada or a placebo.
Exploring other types of PrEP
While the daily use of Truvada is currently the only type of PrEP recommended by health authorities and approved by the U.S. Food and Drug Administration, other types of PrEP may be available in the future. Ongoing clinical trials are investigating the intermittent (that is, non-daily) use of Truvada pills, intermittent or daily use of vaginal and rectal gels, and monthly use of long-lasting injectable drugs and intravaginal rings. Some of these strategies have the potential to improve adherence – which was challenging for many participants in PrEP studies evaluating daily Truvada – and reduce cost and side-effects.
Preliminary results from the IPERGAY study were recently released at CROI. These results were the first to show that an “on-demand,” event-driven PrEP strategy is highly effective for gay men who have frequent sex.
The IPERGAY study
The IPERGAY study was a randomized, placebo-controlled trial that enrolled gay men and other men who have sex with men (MSM) from Montreal (Canada) and several locations in France. The study started in France in January 2012, and Montreal joined the study in July 2013.
Enrollment was restricted to HIV-negative MSM reporting condomless anal sex with at least two different partners in the past six months. Once enrolled, study participants were randomly assigned to one of two groups. Men in one group received Truvada pills (PrEP group) while those in the other group received placebo pills (placebo group). Participants were not informed which group they were in and were asked to take the pills according to the strategy described below.
An “on-demand” PrEP strategy
The study evaluated an “on demand,” event-driven PrEP strategy. This intermittent strategy involved three different doses:
- First dose: two pills (taken at the same time) between two and 24 hours before sex
- Second dose: one pill taken 24 hours after the first dose
- Third dose: a final pill taken 24 hours after the second dose
According to this regimen, each sexual event was associated with four pills, two before sex and two after. However, if a person had sex again before completing all three doses, they were asked to take a pill every 24 hours while sexually active and then finish with the second and third doses after their last sexual event. This meant that participants could end up taking pills on an ongoing, daily basis (as many as eight pills per week) if they were having frequent sex.
Participants were also asked to visit with the study staff every two months. At each visit, men were asked to fill out behavioural questionnaires and were tested for HIV and other sexually transmitted infections (STIs), monitored for side-effects and toxicity, and provided with adherence and risk-reduction services. These risk-reduction services included counselling, condom provision, and post-exposure prophylaxis (PEP).
Overall, 400 men participated in the study: half were randomized to receive Truvada pills while the other half received placebo pills. The average age of participants was 35 and most men were white (94%), employed (84%), had completed secondary education (90%) and described themselves as single (79%).
Many clinical trials have an independent oversight committee called a Data and Safety Monitoring Board (DSMB). The role of a DSMB is to periodically review the data collected from a study and to stop or modify the study if there are concerns about the safety of participants.
In October 2014, the IPERGAY DSMB recommended that men in the placebo group should be offered PrEP. This recommendation was made because it was clear that participants in the PrEP group were at much lower risk of HIV infection. Therefore, it was considered unethical to continue providing placebo. Following this recommendation, the study was changed and placebo pills were no longer provided and Truvada was offered to all participants.
At the time the study was changed, participants had been followed for an average of 13 months. Overall, 16 HIV infections occurred (14 in the placebo group and two in the PrEP group).
The rate of HIV infection in the placebo group was very high (for every 100 men followed for a year, seven HIV infections occurred). This rate was much higher than the study investigators expected. The rate of HIV infection in the PrEP group was 86% lower than the rate in the placebo group, demonstrating that the PrEP strategy was highly effective in preventing HIV transmission.
Rate of pill-taking was measured by counting the number of pills that the participants had not used (men were asked to bring their pill bottles to each study visit). According to these counts, the average (median) number of pills used by participants each month was 16 (equivalent to taking four pills per week). Some participants took as many as 24 pills per month. When asked about pill use during their last sexual event, 28% said they did not take any pills, while the remainder took their pills correctly (43%) or incorrectly (29%). Of note, the two HIV infections in the PrEP group occurred in participants who had not taken any Truvada pills for two months.
Men were also asked about their sexual behaviour during the study. Participants reported having an average of 10 sex acts every month, and about 70% of participants said they did not use condoms the last time they had anal sex. STI rates were high, with over 30% of participants diagnosed with an STI at some point during the study. There were no changes in the number of sex acts or condom use during the study, suggesting PrEP did not lead to increases in HIV risk behaviours.
PrEP was generally safe and well tolerated. Participants in the PrEP group had a slightly higher risk of experiencing gastrointestinal side-effects (such as diarrhea and nausea) compared to those in the placebo group (13% vs. 6%). Two participants taking PrEP had minor degradation of their kidney health.
The “on-demand,” Truvada-based PrEP strategy evaluated in the IPERGAY study was found to be safe, acceptable and highly effective against HIV infection for men in the study.
It is important to note that men in the IPERGAY study had sex frequently and – as a result – took Truvada pills on a regular basis (four pills a week on average). IPERGAY’s “on-demand” PrEP strategy may be less effective for men who have sex less frequently. This is because consistent use of Truvada pills is important to achieve high levels of drugs in the body, which is needed to protect against HIV infection. Indeed, studies show that Truvada needs to be taken every day for seven days in order for drugs to reach maximum levels in the rectum.
Results from the IPERGAY study support other research findings which suggest near daily use of Truvada can provide high levels of protection against HIV. For example, two studies evaluating the daily use of Truvada as PrEP suggested that participants who missed two or three pills a week still maintained a high level of protection against HIV infection. Taken together with IPERGAY, the results from these studies are reassuring for people who are taking daily Truvada as PrEP and occasionally miss a pill or two.
Despite the exciting results from the IPERGAY study, health authorities will likely continue to recommend the daily use of Truvada as PrEP. For example, a statement released by the U.S. Centers for Disease Control and Prevention (CDC) indicated that their organization “continues to recommend daily dosing of PrEP and urges people at substantial risk for HIV infection and their health care providers to continue to follow current CDC guidelines.”
Pre-exposure prophylaxis – CATIE fact sheet
Moving PrEP into practice: an update on research and implementation – Prevention in Focus
Uptake of PrEP in the United States – CATIE News
Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations – World Health Organization
Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline – Centers for Disease Control and Prevention
- Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. New England Journal of Medicine. 2010 Dec 30;363(27):2587–99.
- Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. New England Journal of Medicine. 2012;367(5):399–410.
- Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Science Translational Medicine. 2012;4(151):151ra125.
- Molina J-M, Capitant C, Charreau I, et al. On Demand PrEP With Oral TDF-FTC in MSM: Results of the ANRS Ipergay Trial. In: Program and abstracts of the 22nd Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, USA, Feb 23-26, 2015. Abstract 23LB.
- Grant RM, Anderson PL, McMahan V, et al. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infect Diseases. 2014;14(9):820–29.
- Seifert SM, Glidden DV, Meditz AL, et al. Dose Response for Starting and Stopping HIV Preexposure Prophylaxis for Men Who Have Sex With Men. Clinical Infectious Diseases. 2015;60(5):804–10.