EBioMedicine (Jul 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 trialResearch in context

  • Carolina Herrera,
  • Jennifer Serwanga,
  • Laura Else,
  • Lebina Limakatso,
  • Daniel Opoka,
  • Andrew S. Ssemata,
  • Azure-Dee Pillay,
  • Patricia Namubiru,
  • Thabiso B. Seiphetlo,
  • Geoffrey Odoch,
  • Susan Mugaba,
  • Portia Seatlholo,
  • Amara Alieu,
  • Sujan Dilly Penchala,
  • Richard Muhumuza,
  • Berenice Alinde,
  • Stefan Petkov,
  • Kyle O'Hagan,
  • Christian Callebaut,
  • Janet Seeley,
  • Helen Weiss,
  • Saye Khoo,
  • Francesca Chiodi,
  • Clive M. Gray,
  • Pontiano Kaleebu,
  • Emily L. Webb,
  • Neil Martinson,
  • Julie Fox,
  • Nadia Ahmed,
  • Berenice Alinde,
  • Amara Alieu,
  • Millicent Atujuna,
  • Esther Awino,
  • Linda-Gail Bekker,
  • Christian Callebaut,
  • Francesca Chiodi,
  • Mike Chirenje,
  • Janan Dietrich,
  • Jeffrey Dorfman,
  • Laura Else,
  • Julie Fox,
  • Clive Gray,
  • Christian Holm Hansen,
  • Carolina Herrera,
  • Stefanie Hornschuh,
  • Ayoub Kakande,
  • Pontiano Kaleebu,
  • Charles Kelly,
  • Saye Khoo,
  • Mamkiri Khunwane,
  • Limaktso Lebina,
  • Joseph Makhura,
  • Nomvuyo Mangxilana,
  • Neil Martinson,
  • Susan Mugaba,
  • Richard Muhumuza,
  • Freddie Mukasa Kibengo,
  • Gertrude Mutonyi,
  • Lucia Mungate,
  • Winnie Nabukeera,
  • Rehema Nagawa,
  • Phiona Nalubega,
  • Patricia Namubiru,
  • Stephen Nash,
  • Denis Ndekezi,
  • Teacler Nematadzira,
  • Lumka Nobula,
  • Kyle O'Hagan,
  • Geoffrey Odoch,
  • Daniel Opoka,
  • Sujan Dilly Penchala,
  • Stefan Petkov,
  • Azure-Dee Pillay,
  • Jim Rooney,
  • Elzette Rousseau,
  • Eugene Ruzagira,
  • Alison Sango,
  • Ntombexolo Seatlholo,
  • Janet Seeley,
  • Thabiso Seiphetlo,
  • Jennifer Serwanga,
  • Robin Shattock,
  • Andrew S. Ssemata,
  • Lynda Stranix-Chibanda,
  • Gugulethu Tshabalala,
  • Emily Webb,
  • Helen Weiss

Journal volume & issue
Vol. 93
p. 104648

Abstract

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Summary: 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.

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