State of the Science – HIV Pre-Exposure Prophylaxis (PrEP)

Abstract

HIV remains a significant global health challenge with an estimated 2.6 million people newly infected in 2009. The need of effective HIV prevention interventions are very crucial for controlling the epidemic especially among high-risk populations. Pre-exposure prophylaxis (PrEP) refers to the use of antiretroviral (ARV) medication either oral or topical by HIV-uninfected persons prior to HIV exposure and continue during period of risk to prevent HIV acquisition. The success of ARV drugs in preventing HIV transmission from mothers to infants and in decreasing seroconversion when given to adults shortly after HIV exposure stimulated interest in the concept of PrEP. An effective PrEP could provide an additional safety net to sexually active persons at risk, when combined with other HIV effective prevention strategies. Many clinical researches are ongoing with ARV-based prevention or PrEP in different at risk population across the world including rectal microbicides and ARV-based vaginal ring. In the past few years, of seven PrEP trials with available HIV endpoints, three different products have been tested : tenofivir 1% vaginal gel, oral tenofovirdisoproxilfumarate (TDF) tablets, and TDF/emtricitabine (TDF/FTC or Truvada) tablets. All found the products to be safe, and four (CAPRISA004 as topical gel; and iPrEX, Partners PrEP, and TDF2 as oral PrEP) demonstrated moderate effectiveness for HIV prevention when combined with other HIV prevention strategies. On the other hand, the assessment of oral Truvada in the FEM-PrEP study and of oral and vaginal tenofovir in the VOICE study were stopped for futility by DSMB in 2011. These discrepant results of PrEP studies are perplexing and need further investigated to understand more about these conflict results. It might be possible that drug adherence or whether pharmacologic or local mucosal factors or others explained these variable efficacy estimates. More challenging issues to come even PrEP can demonstrate the effectiveness to minimize the risk of HIV infection, but numerous questions will remain about its implementation outside of the research context; such as intermittent use of the drugs, inducing drug resistance, drug safety for long-term use, costs of drug and appropriate monitoring program, risk compensation and combination with other effective HIV prevention methods.