[HIV preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine: What about safety?]

Abstract

Introduction: Pre-exposure prophylaxis (PrEP) is a combination of antiretroviral regimen, tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) that has been shown to prevent HIV transmission. It had been regulated through a temporary recommendation use since December 2015 and had marketing authorization in France since March 2017. As, this product is proposed for adults and adolescents safe from HIV but at high risk of infection, the question is to know if there is a safety concern about this use.

Methods: A request has been made in the French national pharmacovigilance database (ANPV) and VIGILYZE for an extraction of all cases containing TDF/FTC as suspect drugs in PrEP use. In the second part, we did a literature review in PubMED with MeSH terms and an analysis of the results of the American, English and French initial clinical trials was performed.

Results: In both database, 808 cases correspond to an indication of HIV prexposure prophylaxis who represent 2058 adverse effects (AEs) mainly distributed in gastro-intestinal disorders (38.5%), general disorders (16.8%) and 62 cases of seroconversion. We identify 24% of unexpected AEs including 12% of serious AEs in the French database. In literature review, there are no unexpected AEs published, the AEs are mainly gastro-intestinal disorders. There was no significant difference in the AE profile compared to the HIV-infected population treated with TDF/FTC.

Conclusion: Data from the ANPV, combined with data from the worldwide pharmacovigilance database, show that the most commonly observed AEs are gastrointestinal, mainly nausea, vomiting and diarrhea. A significant number of asthenia and fatigue are also observed. These AEs are well described in the SMPc. However, we have little data, which can be explained by a probable under-reporting of AEs. We identify 24% of unexpected and potentially serious adverse effects in France mainly among chemsex users. Based on these results, our study confirms the safety of PrEP.

Keywords: HIV; Pharmacovigilance; PrEP; Safety; TDF/emtricitabine.