Thesis title: Incidence of HIV drug resistance in the context of PrEP use
In June 2016 in Europe, emtricitabine and tenofovir disoproxil (FTC/TDF) was first approved for Pre-exposure prophylaxis (PrEP), in combination with safer sex practices, to reduce the risk of sexually acquired HIV-1 in adults at high risk for FTC/TDF. The two main studies supporting the efficacy of FTC/TDF for HIV-1 PrEP usage were the randomised, double-blind and placebo controlled: iPrEx Study and Partners PrEP Study (Baetan et al 2012;Grant et al 2012). The available data from both the two main studies show the efficacy of FTC/TDF for HIV-1 PrEP usage, when acute HIV-infection is ruled out before starting PrEP.
According to WHO recommendations, PrEP containing the antiretroviral drug, TDF, could be offered as an additional prevention choice for people at substantial risk of HIV infection as part of combination HIV prevention approaches (strong recommendation, high-quality evidence). The treatment includes the daily use of specific oral antiretrovirals to prevent the virus from establishing a permanent infection (ECDC guideline).
Antiretroviral resistance is a potential public health issue with FTC/TDF PrEP, as a single mutation in the HIV genoma confers high-level resistance to treatment. Resistance has been observed in vitro, and in some HIV-1 infected patients, due to the development of the M184V/I mutation with FTC or the K65R mutation with TDF. Resistance to FTC or TDF has also been rarely detected in sero-converters from FTC/TDF PrEP registration trials.
During PhD attendance period, my research was focused on obtaining information on the association between adherence to FTC/TDF PrEP and new HIV-1 infection and describe resistance in individuals who developed new HIV-1 infections while on PrEP. Up to 31 December 2021, post-marketing cases of suspected adverse drug reactions associated to the PTs ”drug ineffective” or “drug resistance” were retrieved for FTC/TDF containing products from the Eudravigilance database and the safety finding from 4 observational studies requested as category 3 in the Risk management plan for FTC/TDF submitted as part of a marketing application to obtain more information on the efficacy of FTC/TDF for HIV-1 PrEP
Antiretroviral resistance is thus a safety concern of the TDF/FTC PrEP that needs continuous monitoring. Of particular concern is the fact that PrEP uses the same antiretroviral drugs that are currently included in ART for patients with HIV.
Selection of drug resistance after PrEP failure could compromise ART efficacy