A Phase I clinical trial comparing a daily regimen of antiretroviral pre-exposure prophylaxis (PrEP) with an intermittent regimen found that rates of adherence to intermittent dosing regimens were lower than adherence to daily dosing. The study is the first ever to report data on intermittent antiretroviral PrEP use in humans. The results from this trial were published on April 12 in PLOS One*, and preliminary findings were presented at the 2010 International AIDS Society Conference in Vienna.
The trial involved 67 African men who have sex with men (MSM) and 5 female sex workers, and compared the safety, acceptability and adherence profiles of the antiretroviral drug Truvada administered in daily or intermittent regimens. The intermittent regimen was taken on Monday, Friday and within two hours following sex (post-coital) not to exceed one dose per day. The study was conducted by researchers at the Kenya AIDS Vaccine Initiative in Kangemi and the Kenya Medical Research Institute-Centre for Geographic Medicine Research-Coast in Kilifi, and was sponsored by the International AIDS Vaccine Initiative (IAVI). The antiretroviral drug used in the study, Truvada—a combination of tenofovir and emtricitibine—was provided by its manufacturer, Gilead Sciences.
The study found that adherence rates to the daily regimen were 83%, while fixed intermittent dosing had an adherence rate of 55%, and adherence to post-coital dosing was 26%. Adherence to the study drug regimens in this trial was measured using the medication event monitoring system (MEMS)—an electronic pill cap that records each instance in which the pill container is opened—as well as monthly follow-up interviews. Daily text messages (SMS) were used to collect data on sexual behavior in order to estimate post-coital adherence. The lower adherence rate to the post-coital doses in the intermittent regimen suggests that post-coital dosing may be challenging in the populations included in this trial. However it may also reflect difficulties in accurately measuring post-coital dosing using MEMS or self-report data. Further study will be needed to determine whether the intermittent use of Truvada as pre-exposure prophylaxis will be a viable HIV-prevention strategy for MSM and female sex workers in Africa. Currently, few studies address adherence to non-daily medication regimens, and these findings will be useful to future studies examining the intermittent use of PrEP for HIV prevention.
This was the first study to examine the use of SMS reporting of sexual behavior in a clinical trial, and it found relatively low response rates. SMS could potentially be an effective strategy for collecting sexual behavior data, however challenges will need to be addressed to improve the feasibility of using this technology for data collection, including technical issues such as server outages and network problems, as well as volunteer technical or acceptability factors.
IAVI and its partners initiated this trial to explore adherence to PrEP in the high-risk populations that are expected to participate in HIV vaccine efficacy trials. “This study contributes to the growing body of research on the use of PrEP as an HIV-prevention strategy, particularly among at-risk groups in Africa,” said Eduard Sanders, study co-author and clinical researcher at Center for Geographical Medicine Research, Coast in Kilifi, Kenya. “Given the cost, adherence and potential toxicity concerns associated with PrEP administered on a daily basis, intermittent PrEP regimens could be a desirable alternative. However, depending on the population, intermittent regimens may have suboptimal adherence, and further research is required to determine whether this strategy will be feasible in vulnerable populations at risk of HIV infection.”
The AIDS pandemic ranks among the most devastating ever recorded in history. Since its start, more than 60 million people have been infected with HIV and some 30 million have died from HIV-related causes. A comprehensive response that combines proven, existing HIV-prevention methods, ARV treatment for people currently living with HIV, and the development and widespread use of new HIV-prevention technologies will be essential to ending the devastation wrought by HIV and AIDS. Ending the AIDS pandemic remains one of the biggest challenges of our time, and developing effective tools for the prevention of HIV will require sustained political, social and financial commitment and support.
* PLoS One. 2012;7(4):e33103. Epub 2012 Apr 12v