Nondaily preexposure prophylaxis for HIV prevention

Abstract

Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence.

Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model

“…The back-up systemic drug and biodistribution of drug to sanctuary sites (lymph node, spleen and brain etc.) is an effective strategy to prevent and eradicate virus within the biological system (23, 24), which was accomplished in this study. Sanctuary sites include areas within the body with reduced ARV penetration compared to plasma (23).…”

Pre-exposure prophylaxis (PrEP) for men who have sex with men in Europe: review of evidence for a much needed prevention tool

“…In the IPERGAY trial, monthly pill use varied in most participants, possibly reflecting such changes in perceived risk 6 33. Periods associated with increased sexual risk include travelling,34 leaving home or moving to another city, coming out as an MSM and ending a relationship 35.…”

“…Periods associated with increased sexual risk include travelling,34 leaving home or moving to another city, coming out as an MSM and ending a relationship 35. Such non-daily regimens could eventually lead to a decrease in the overall number of pills used, and as a result reduce cost, possibly leading to less side effects and would be more suitable for persons with infrequent risky sex 31 33. Disadvantages may be that it is more complicated, requires advanced sex planning and that it is less forgiving for missed doses 33 36.…”

“…Such non-daily regimens could eventually lead to a decrease in the overall number of pills used, and as a result reduce cost, possibly leading to less side effects and would be more suitable for persons with infrequent risky sex 31 33. Disadvantages may be that it is more complicated, requires advanced sex planning and that it is less forgiving for missed doses 33 36. Enabling users to cover periods and situations of high risk for HIV, regardless of which PrEP dosing regimen is a challenge that needs to be addressed by future implementation programmes.…”

Profilaxia Pré-Exposição ao VIH

“…18 Esta estratégica posológica pretendia aumentar a adesão terapêutica, reduzir potenciais efeitos adversos e reduzir custos. 22 No estudo Inglês PROUD conclui-se que seria necessário tratar 13 indivíduos HSH com história de sexo anal sem preservativo nos 90 dias anteriores, durante um ano, para evitar uma nova infeção por VIH. 17 No estudo IPERGAY esse número seria de 18.…”