Abstract
Number studies have shown that the prophylactic use of tenofovir disoproxil (TDF) can significantly reduce the number of new HIV and hepatitis B infections. However, the risk of TDF-associated severe renal adverse events may hamper the implementation of these new prevention strategies. This thesis aims to evaluate the impact on renal function of TDF in the setting of HIV pre-exposure prophylaxis (PrEP) and prevention of mother-to-child transmission (PMTCT) of HBV.The cohort study conducted among 3000 PrEP users followed at the Saint Louis Hospital in Paris demonstrate that the risk of acute renal failure was low and mainly concerned users with an age > 50 years and/or with an estimated glomerular filtration rate < 90mL/min at the time of prophylaxis initiation. All these users were able to continue using PrEP with a low risk of relapse. The analysis conducted in the randomized placebo-controlled Ipergay clinical trial, as well as in the ANRS-Prévenir cohort study in the Ile de France area, highlights that the use of "on-demand" HIV PrEP in men who have sex with men improved the renal safety of the prophylaxis by reducing individuals' exposure to TDF. This dosing regimen can reduce the risk of renal toxicity among individuals with risk factors of kidney injury. Data from these studies allowed the development of recommendations for renal function monitoring among PrEP users. These recommendations emphasize the need to individualize renal function monitoring and support the shift towards differentiated PrEP service delivery and models involving non-medical healthcare providers. This approach will be crucial to significantly increasing the number of PrEP users and should facilitate adherence and persistence in treatment.Concerning the PMTCT of HBV, we specifically assessed the risk of TDF-associated tubulopathy, given the harmful effect of tubular dysfunction on maternal and infant health. Using early kidney injury markers on urine samples collected in a randomized, double-blind, placebo-controlled clinical trial conducted in Thailand (iTAP), we show that TDF is not associated with a significant increase of tubulopathy and that TD can be used safely during the third trimester of pregnancy and breastfeeding. This confirms that the PMTCT of hepatitis B among women at high risk of transmission can be implemented by non-specialists in many settings.Overall, this thesis highlights that the risk of TDF-associated renal toxicity in the setting of HIV and hepatitis B prevention does not stand as a barrier to the implementation of these new preventive strategies in low-income countries that cannot perform regular monitoring of renal function.