Pre-Exposure Prophylaxis in HIV Prevention

Pre-exposure prophylaxis (PrEP) employs antiretroviral agents in HIV-negative individuals to avert viral acquisition. Initial efficacy trials of daily oral regimens combining emtricitabine and tenofovir disoproxil fumarate demonstrated substantial risk reductions when adherence was high. Over the past decade, adaptations such as event-driven or on-demand dosing schedules have been validated to align prophylactic coverage with sporadic exposure in key populations. Pharmacokinetic and pharmacodynamic studies have defined the drug concentration thresholds in blood and mucosal tissues necessary for protection, informing dose timing and formulation development. Concurrent implementation research has identified barriers to uptake and adherence, including access constraints and regimen fatigue, driving the pursuit of long-acting injectables, vaginal rings and on-demand inserts that combine contraceptive and antiviral functions. These innovations address global disparities in sexual health services by offering discrete, user-controlled options. A comprehensive, evidence-based strategy that integrates behavioural support, community engagement and novel delivery platforms is essential for maximising PrEP’s public health impact and moving towards HIV epidemic control.

Research from Nature Portfolio

Recent model-based analyses have integrated data across clinical trials to elucidate adherence–efficacy relationships for oral PrEP in cisgender women. These studies show that protection against HIV can exceed 90% when a sufficient proportion of doses are taken, even if perfect daily adherence is not achieved. By simulating diverse patterns of pill-taking behaviour, the models reconcile previously inconsistent trial outcomes and highlight that behavioural factors rather than biological sex-specific pharmacology primarily drive differences in efficacy. This framework offers an evidence-based approach to tailor adherence interventions, interpret trial heterogeneity and inform public health guidelines for optimal PrEP implementation in resource-limited settings.

Pre-Exposure Prophylaxis in HIV Prevention publication trend

The graph below shows the total number of articles in pre-exposure prophylaxis in hiv prevention across all publications each year (not limited to Nature Index journals).

Technical terms

Pre-exposure prophylaxis (PrEP): Prevention strategy involving antiretroviral drug use by HIV-negative individuals before potential exposure.

On-demand PrEP: Prophylactic regimen timed around periods of anticipated risk rather than daily administration.

Adherence: Extent to which a user follows the prescribed dosing schedule.

Pharmacokinetics (PK): Study of drug absorption, distribution, metabolism and elimination in the body.

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF): Fixed-dose combination of antiretrovirals used in oral PrEP formulations.

Tenofovir alafenamide (TAF): Prodrug of tenofovir engineered for enhanced intracellular delivery and reduced systemic exposure.

References

1. Model-based predictions of protective HIV pre-exposure prophylaxis adherence levels in cisgender women. Nature Medicine (2023).
2. Dose finding study for on-demand HIV pre-exposure prophylaxis for insertive sex in sub-Saharan Africa: results from the CHAPS open label randomised controlled trial. EBioMedicine (2023).
3. Preclinical and Early Clinical Development of Tenofovir Alafenamide/Elvitegravir Topical Inserts for Effective On-Demand Vaginal and Rectal HIV Prevention. Pharmaceutics (2024).