02 Dec Sexual Activity Based Antiretrovirals Reduce HIV in MSM
MedicalResearch.com Interview with:
Dr Jean-Michel Molina
Department of Infectious Diseases
Saint-Louis Hospital and University of Paris Diderot
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Molina: Men who have sex with men (MSM) are disproportionately affected by HIV worldwide and represent the today in Europe the largest group in which new HIV infections are diagnosed with no decrease over the last 8 years.
The first study assessing preexposure prophylaxis (PrEP) efficacy among MSM was published in 2010 (the Iprex study) which reported for the first time a 44% reduced incidence of HIV in those randomized to receive daily tenofovir/emtricitabine TDF/FTC (one pill per day) as compared to placebo. Adherence to a daily pill regimen was found to be challenging however since only half of the participants (according to drug detection in blood) were taking their daily regimen. Post-hoc analyses suggested that among those with drugs detectable in plasma, PrEP efficacy could be as high as 92%. However, long term adherence to a daily regimen represents the Achille’s heel of daily PrEP, as shown later in other large PrEP trials among women in Africa (VOICE and Fem-PrEP).
Based on data from animal models we wished to assess whether PrEP with TDF/FTC taken on demand, at the time of sexual activity, could improve adherence, thereby efficacy and also improve safety and cost.
In this randomized double blind placebo controlled trial, on demand PrEP with TDF/FTC reduced the incidence of HIV by 86% in the intent to treat analysis as compared to placebo, and the only 2 participants who became infected in the TDF/FTC arm after more than a year of follow-up, had discontinued the use of PrEP months before infection.
The ANRS Ipergay study reports therefore a very high efficacy of PrEP, similar to that also reported in another PrEP study carried out in the UK among MSM with daily TDF/FTC (PROUD), which results were disclosed at the same time. Both studies have increased awareness about the real potential of PrEP and have had a strong impact on WHO and European guidelines.
Medical Research: What should clinicians and patients take away from your report?
Dr. Molina: First, the incidence of HIV-infection in the placebo arm was much higher than expected, underscoring the need to improve HIV prevention in this population of high risk MSM.
Second, on demand PrEP with TDF/FTC can drastically reduce the risk of HIV acquisition in this population and represent therefore an alternative to daily PrEP. So Gay men have now more choices to prevent HIV infection, use of condoms, daily or on demand PrEP.
Third, although the safety of this regimen was good, clinical and lab monitoring (creatinine clearance) is required on a 2 to 3 months basis, also to detect and treat other sexually transmitted infections and deal with drug addictions and psychiatric diseases which are frequent in this population.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Molina: We first need to develop new delivery modalities for PrEP so that people at risk could choose the PrEP regimens that would be more suitable for them. Studies assessing gels (rectal or vaginal), films, vaginal rings (where antiretroviral can be combined with contraceptives), injectable agents and also implants are in process. Also, new oral drugs for PrEP should be developed with an improved safety profile and long half-life allowing for a reduced pill burden.
At the same time we need to implement operational research to deliver PrEP to all in need, increase awareness for PrEP and combine PrEP with other preventive tools. PrEP is indeed an opportunity to improve prevention against HIV.
Finally, PrEP combined with upscaled testing for HIV, and early treatment of those already infected, should help us to reach the UNAIDS’ goal of no new infection by 2030.
On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection
December 1, 2015
Dr Jean-Michel Molina (2015). Sexual Activity Based Antiretrovirals Reduce HIV in MSM