Herrera, Carolina; Serwanga, Jennifer; Else, Laura; Limakatso, Lebina; Opoka, Daniel; Ssemata, Andrew S; Pillay, Azure-Dee; Namubiru, Patricia; Seiphetlo, Thabiso B; Odoch, Geoffrey; +19 more... Mugaba, Susan; Seatlholo, Portia; Alieu, Amara; Penchala, Sujan Dilly; Muhumuza, Richard; Alinde, Berenice; Petkov, Stefan; O'Hagan, Kyle; Callebaut, Christian; Seeley, Janet; Weiss, Helen; Khoo, Saye; Chiodi, Francesca; Gray, Clive M; Kaleebu, Pontiano; Webb, Emily L; Martinson, Neil; Fox, Julie; CHAPS; (2023) 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. eBioMedicine, 93. 104648-. ISSN 2352-3964 DOI: https://doi.org/10.1016/j.ebiom.2023.104648
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Abstract
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: EDCTP2, Gilead Sciences, Vetenskapsrådet.
Item Type | Article |
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Faculty and Department |
Faculty of Public Health and Policy > Dept of Global Health and Development Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology & International Health (2023-) MRC Uganda > UG-HIV Care |
PubMed ID | 37327677 |
Elements ID | 205124 |
Official URL | http://dx.doi.org/10.1016/j.ebiom.2023.104648 |
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