HIV preexposure prophylaxis: walking ahead on tightropes.

The National HIV Surveillance Report estimated that by the end of 2008, there were approximately 1.2 million people living with human immunodeficiency virus (HIV) in the United States. Despite the decline in mortality from HIV, the incidence rate has remained steady, at approximately 50,000 cases per year. These startling incidence numbers speak of our helplessness in containing HIV transmission, fostering efforts toward developing robust prevention strategies. Earlier approaches focused on the consistent use of barrier methods, mandatory HIV blood bank screening, behavior modification, and postexposure prophylaxis. Of late, adult male circumcision, HIV vaccination, and vaginal microbicide have been assessed in various trials with varying outcomes. There is no doubt that antiretroviral therapy (ART) has proven effective and remains promising in curbing the spread of HIV infection. The Preexposure Prophylaxis Initiative study showed significant protection in a population at high risk, specifically men who have sex with men. Preliminary results of ongoing oral preexposure prophylaxis (PrEP) studies TDF2 and Partners PrEP confirmed protection against HIV transmission in women. In the Partners PrEP study, tenofovir (TDF) was effective in 68% of women and 58% of men versus placebo, and TDF/emtricitabine (TDF/FTC) was effective in 62% of women and 83% of men. None of the differences between men and women or between TDF and TDF/FTC was statistically significant. In the TDF2 trial, TDF/FTC was effective in 80% of men, compared with an efficacy of 49% in women; however, the study was underpowered to assess the difference between the two groups. These studies have incited international attention toward oral PrEP as a plausible answer to curb the HIV incidence rate. Many PrEP trials to assess this novel tool are under way (Table). Furthermore, the Joint United Nations Programme on HIV/AIDS has dedicated US$ 1.19 billion funding for HIV prevention research, focused mainly on ART PrEP, HIV vaccine development, vaginal microbicide, and male circumcision intervention. In this issue of the Southern Medical Journal, Tripathi et al present a questionnaire survey to assess health care providers’ knowledge, attitudes, and perceptions regarding PrEP in two southern US states. The results are remarkable for the high degree of acceptability and support for the future implementation of PrEP. A high percentage of respondents agreed with empowering women for the prevention of HIV transmission. This is a pertinent and often overlooked determinant in HIV transmission. In Sub-Saharan Africa, where the majority of new HIV infections occur, women represent nearly 60% of adults and in most cases acquire HIV through sexual intercourse with an infected male partner. PrEP may help address the urgent need for a female-controlled prevention method worldwide for women who are unable to negotiate condom use with their partners. The study is timely because it can help identify unmet needs, gaps in knowledge, cultural beliefs, or behavioral patterns in the study area. In turn, this would facilitate optimal resource use, augment strategic decision-making capability by the authorities, and help customize implementation tools when PrEP is implemented at the grassroots level. Interestingly, Tripathi et al conducted this study before the availability of the results of major PrEP trials. Higher acceptance rates may be expected among the respondents if the study were to be conducted now, given the encouraging results of various PrEP studies. Implementation of PrEP is marred by various formidable challenges. Its use is likely to be limited to the population of individuals at high risk. The unknown safety profile of longterm ART, especially TDF/FTC in HIV-uninfected individuals, is concerning. Other deterrents include enforcing strict adherence among users, high-cost involvement that would limit its utility in resource-restricted settings, development of multidrug-resistant viral infection in case of PrEP failure, determination of the optimal frequency of testing and safety monitoring, and risk compensation. A holistic approach that integrates the available prevention strategiesVbehavioral changes, consistent condom use, timely diagnosis and treatment of sexually transmitted diseases, regular testing for HIV, monogamy, and PrEPVare plausible steps toward containing the incidence of HIV. Although PrEP certainly appears to be a step forward in the battle against HIV, it may inadvertently be a step backward if it results in overzealous risk compensation, drug resistance, and exorbitant costs of development and implementation. A highly cautious interpretation of results of PrEP trials, especially at the implementation level, is warranted. Editorial