Ex vivo rectal tissue infection with HIV-1 to assess time to protection following oral PrEP with TDF/FTC (a sub-study of the ANRS PREVENIR study)

Abstract

Objectives: We wished to assess time to protection from HIV-1 infection following oral tenofovir disoproxil and emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP), using ex vivo rectal tissue infections and drug concentration measures in blood and rectal tissue. Design/Methods: Participants from the ANRS PREVENIR study (NCT03113123) were offered this sub-study after a 14-day wash-out. We used an ex vivo model to evaluate rectal tissue HIV-1 susceptibility before and after PrEP, two hours after 2 pills or seven days of a daily pill of TDF/FTC. PrEP efficacy was expressed by the difference (after-before) of 14-day cumulative p24 antigen levels. TFV-DP and FTC-TP levels were measured in rectal tissue and PBMCs and correlated with HIV-1 infection. Results: Twelve and eleven males were analysed in the 2 hours–double dose and 7 days–single dose groups, respectively. Cumulative p24 differences after-before PrEP were -144pg/ml/mg (IQR[-259;-108]) for the 2 hours–double dose group (p = 0.0005) and -179pg/ml/mg (IQR[-253;-86]) for the 7 days–single dose group (p = 0.001), with no differences between groups (p = 0.93). Rectal TFV-DP was below quantification after a double dose, but FTC-TP levels were similar to levels at seven days. There was a significant correlation between rectal FTC-TP levels and p24 changes after a double dose (R = -0.84; p = 0.0001). Conclusions: Oral TDF/FTC provided similar protection against HIV-1 infection of rectal tissue 2 hours after a double dose or 7 days of a daily dose. At 2 hours, this protection seems driven by high FTC-TP concentrations in rectal tissue. This confirms the importance of combining TDF and FTC to achieve early protection.