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Unlocking the Potential of Post-Exposure Prophylaxis (PEP) for HIV Prevention: A Comprehensive Review of New Drugs, Approaches, and Ongoing Challenges

Shot of a young woman doing inventory in a pharmacy on a digital tablet with her colleague in the background

PEP, or post-exposure prophylaxis, is a course of medication taken after a potential HIV exposure to prevent infection. It has been a critical tool in preventing HIV acquisition for over three decades since the discovery of the efficacy of zidovudine. A new review published in The Lancet HIV journal addresses the reason PEP remains underutilized globally despite its proven effectiveness. Recent clinical trials have introduced better-tolerated PEP regimens, particularly those featuring integrase strand transfer inhibitors (INSTIs), but these advancements have not been widely adopted. 

The historical journey of PEP began with the use of zidovudine in preventing HIV among healthcare workers. Subsequent studies in non-occupational settings, particularly among men who have sex with men (MSM), further supported PEP’s use. Despite its success, challenges such as side effects and premature discontinuation hindered its broader adoption. 

The evolution of PEP guidelines reflects advancements in HIV care. While the initial focus was on zidovudine and lamivudine, contemporary guidelines favor tenofovir-based regimens and INSTIs. Earlier studies explored PEP regimens containing protease inhibitors, while generally effective, had tolerability and completion rate challenges.  The recommended 28-day duration of treatment has remained unchanged, based on early animal studies. 

Challenges persist in PEP research, with the need for placebo-controlled studies to establish efficacy complicated by ethical considerations. There is variability in completion rates and side-effect profiles across different PEP regimens. The article emphasizes the importance of safety monitoring during PEP, potential drug interactions, and the role of observational studies in understanding PEP adherence and risk profiles. PEP research continues to evolve, considering newer, better-tolerated medications, new insights from animal models, and the potential role of PEP as a gateway to pre-exposure prophylaxis (PrEP), the use of antiretroviral medication taken regularly to prevent HIV. 

The article discusses new data and questions surrounding the duration of PEP regimens, highlighting recent animal studies suggesting regimens lasting less than 28 days might offer high levels of protection. Given that more than 1.5 million new HIV infections occurred since 2022, PEP continues to be underused globally, in large part because of insufficient access, knowledge, and awareness. The focus in the short term should be on educating healthcare providers and communities and optimizing the benefits of the initial PEP encounter. Healthcare providers need to understand how to use the PEP encounter to educate those seeking PEP about their risks, and to assess whether the transition to PrEP (pre-exposure prophylaxis) is appropriate. The article concludes by emphasizing the need for collective efforts to unlock the full potential of PEP in the global fight against HIV/AIDS. 


You can read the review “Post-exposure prophylaxis to prevent HIV: new drugs, new approaches, and more questions” online (Note: the full case study is behind a paywall). 

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