Adherence challenges with drugs for pre-exposure prophylaxis to prevent HIV infection
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Background There are 34 million people living with human immunodeficiency virus (HIV) worldwide and each year this number increases. Until a vaccine is discovered, the prevention of new HIV infections remains an urgent priority. Several trials studying the use of oral and topical agents for the prevention of HIV infection have already been completed. Adherence has proved to be a major challenge in achieving product efficacy. Aim of the review To provide the clinical pharmacist with an understanding of the oral pre-exposure prophylaxis (PrEP) and topical microbicide product pipeline whilst emphasizing the critical importance of adherence to these drugs to avert HIV infection. Methods PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were searched using appropriate key words. For the time period 1992–2013—all phase II and phase III safety and effectiveness studies—testing agents for prevention of HIV infection were included in the review. Efficacy estimates, adherence estimates and reported challenges with adherence were extracted. Results Twenty-four phase II and III clinical trials were found during review. Of these, 20 trials have been completed, and six trials show effectiveness in preventing HIV infection. The majority of the successful trials were to oral PrEP and to date only one microbicide trial of a vaginal antiretroviral microbicide gel has showed effectiveness. Adherence to study product played a major role in trial outcomes and there are several reasons for non-adherence. These include high on-trial pregnancy rates, low trial retention rates, low participant perception of risk, participant characteristics such as age <25 years, single status, migratory partners and trial fatigue. Study product characteristics such as dosage form, dosing interval, as well as associated adverse events may also influence adherence. Conclusion Moderate to high adherence is critical to demonstrate efficacy of drugs for HIV prevention. For topical agents, intermittent use associated with coitus is more effective than daily use, particularly if sex is infrequent or partners migrant. For oral agents, daily use is effective but the motivation to use the drug and high risk perception is important. In serodiscordant couples, early initiation of highly active antiretroviral therapy in the infected partner affords almost complete protection to the negative partner. Drugs need to be tailored to the population at risk and availability of multiple drug options are important.
KeywordsAdherence Clinical trial HIV prevention Microbicides PrEP
CAPRISA is supported by the National Institute of Allergy and infectious Disease (NIAID), National Institutes of Health (NIH) (Grant No. AI51794). The authors were study personnel in the CAPRISA 004 and CAPRISA 008 Tenofovir gel trials, which was supported by the United States Agency for International Development (USAID), Family Health International (FHI), CONRAD and LIFElab, a biotechnology centre of the South African Department of Science & Technology. The Columbia University-Southern African Fogarty AIDS International Training and Research Programme (AITRP Grant # D43TW00231) has supported Tanuja N Gengiah’s professional development. The views expressed by the authors do not necessarily reflect the views of NIH, USAID, CONRAD, FHI360 or Gilead Sciences.
Conflicts of interest
The authors have no conflicts of interest to declare.
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