{Reference Type}: Randomized Controlled Trial
{Title}: Dose finding study for on-demand HIV pre-exposure prophylaxis for insertive sex in sub-Saharan Africa: results from the CHAPS open label randomised controlled trial.
{Author}: Herrera C;Serwanga J;Else L;Limakatso L;Opoka D;Ssemata AS;Pillay AD;Namubiru P;Seiphetlo TB;Odoch G;Mugaba S;Seatlholo P;Alieu A;Penchala SD;Muhumuza R;Alinde B;Petkov S;O'Hagan K;Callebaut C;Seeley J;Weiss H;Khoo S;Chiodi F;Gray CM;Kaleebu P;Webb EL;Martinson N;Fox J; ;
{Journal}: EBioMedicine
{Volume}: 93
{Issue}: 0
{Year}: 2023 Jul 14
{Factor}: 11.205
{DOI}: 10.1016/j.ebiom.2023.104648
{Abstract}: <B>BACKGROUND: </B>The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown.<BR><B>METHODS: </B>HIV-negative males 13-24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge.<BR><B>RESULTS: </B>144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24day15 geometric mean ratio 1.06, 95% confidence interval: 0.65-1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin.<BR><B>CONCLUSIONS: </B>A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted.<BR><B>BACKGROUND: </B>EDCTP2, Gilead Sciences, Vetenskapsrådet.