Pre-Exposure Prophylaxis to Prevent HIV Infection: Current Status, Future Opportunities and Challenges
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As the global incidence of HIV exceeds 2 million new infections annually, effective interventions to decrease HIV transmission are needed. Randomized, placebo-controlled studies have demonstrated that daily oral antiretroviral pre-exposure prophylaxis (PrEP) with a fixed-dose combination tablet containing tenofovir disoproxil fumarate and emtricitabine can significantly reduce HIV incidence among diverse at-risk populations. In these studies, the efficacy of PrEP was correlated with levels of adherence. Official guidelines recommend provision of PrEP to people at greatest risk of HIV acquisition, and demonstration projects suggest that high levels of uptake and adherence are possible outside of controlled studies. However, several potential barriers to implementing PrEP remain. These challenges include low awareness and utilization of PrEP by at-risk individuals, uncertainty about adherence in ‘real-world’ settings, the majority of healthcare providers being untrained in PrEP provision, limited data about potential adverse effects from long-term use of tenofovir–emtricitabine, high costs of PrEP medications, and stigma associated with PrEP use and the behaviors that would warrant PrEP. Innovative pharmacologic chemoprophylactic approaches could provide solutions to some of these challenges. Less-than-daily oral dosing regimens and long-acting injectable medications could reduce pill burdens and facilitate adherence, and local delivery of PrEP medications to genital compartments via gels, rings and films may limit systemic drug exposure and potential toxicities. As the portfolio of chemoprophylactic agents and delivery systems expands to meet the diverse sexual health needs and product preferences of individuals who may benefit from PrEP, it is hoped that antiretroviral chemoprophylaxis could become an acceptable, feasible, and highly effective addition to existing HIV prevention strategies.
KeywordsTenofovir Tenofovir Disoproxil Fumarate Maraviroc Rilpivirine PrEP Medication
Funding: Douglas S. Krakower receives funding from the National Institutes of Health (K23 MH098795), and Kenneth H. Mayer receives funding from the Harvard University Center for AIDS Research (CFAR), a National Institutes of Health-funded program (P30 AI060354; PI: Walker).
Potential competing interests
Drs. Krakower and Mayer have conducted research with unrestricted Grants from Gilead Sciences (DSK and KHM), Bristol Myers Squibb (DSK and KHM), ViiV (KHM) and Merck (KHM). Drs. Krakower and Mayer have co-authored a continuing medical education (CME) activity for Medscape.
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