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.

Male Humans HIV Infections / prevention & control Anti-HIV Agents / therapeutic use Pre-Exposure Prophylaxis Leukocytes, Mononuclear Emtricitabine Africa South of the Sahara
Adolescents Foreskin HIV-1 Oral PrEP PK/PD Tissue explants

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Jul 2023
Historique:
received: 08 02 2023
revised: 26 05 2023
accepted: 27 05 2023
medline: 17 7 2023
pubmed: 17 6 2023
entrez: 16 6 2023
Statut: ppublish

Résumé

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. 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-1 144 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 (p24 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. EDCTP2, Gilead Sciences, Vetenskapsrådet.

Sections du résumé

BACKGROUND 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 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-1
FINDINGS RESULTS
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 (p24
INTERPRETATION CONCLUSIONS
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 BACKGROUND
EDCTP2, Gilead Sciences, Vetenskapsrådet.

Identifiants

DOI: 10.1016/j.ebiom.2023.104648 PMID: 37327677 PMC: PMC10275696
pubmed: 37327677
pii: S2352-3964(23)00213-X
doi: 10.1016/j.ebiom.2023.104648
pmc: PMC10275696
pii:
doi:

Substances chimiques

Anti-HIV Agents 0
3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate QBP25342AG
Emtricitabine G70B4ETF4S

Types de publication

Randomized Controlled Trial Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104648

Subventions

Organisme : Medical Research Council
ID : MC_UU_00027/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00033/1
Pays : United Kingdom

Investigateurs

Nadia Ahmed (N)
Berenice Alinde (B)
Amara Alieu (A)
Millicent Atujuna (M)
Esther Awino (E)
Linda-Gail Bekker (LG)
Christian Callebaut (C)
Francesca Chiodi (F)
Mike Chirenje (M)
Janan Dietrich (J)
Jeffrey Dorfman (J)
Laura Else (L)
Julie Fox (J)
Clive Gray (C)
Christian Holm Hansen (CH)
Carolina Herrera (C)
Stefanie Hornschuh (S)
Ayoub Kakande (A)
Pontiano Kaleebu (P)
Charles Kelly (C)
Saye Khoo (S)
Mamkiri Khunwane (M)
Limaktso Lebina (L)
Joseph Makhura (J)
Nomvuyo Mangxilana (N)
Neil Martinson (N)
Susan Mugaba (S)
Richard Muhumuza (R)
Freddie Mukasa Kibengo (FM)
Gertrude Mutonyi (G)
Lucia Mungate (L)
Winnie Nabukeera (W)
Rehema Nagawa (R)
Phiona Nalubega (P)
Patricia Namubiru (P)
Stephen Nash (S)
Denis Ndekezi (D)
Teacler Nematadzira (T)
Lumka Nobula (L)
Kyle O'Hagan (K)
Geoffrey Odoch (G)
Daniel Opoka (D)
Sujan Dilly Penchala (SD)
Stefan Petkov (S)
Azure-Dee Pillay (AD)
Jim Rooney (J)
Elzette Rousseau (E)
Eugene Ruzagira (E)
Alison Sango (A)
Ntombexolo Seatlholo (N)
Janet Seeley (J)
Thabiso Seiphetlo (T)
Jennifer Serwanga (J)
Robin Shattock (R)
Andrew S Ssemata (AS)
Lynda Stranix-Chibanda (L)
Gugulethu Tshabalala (G)
Emily Webb (E)
Helen Weiss (H)

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests CH has received research grants from EDCTP, Vetenskapsrådet and Gilead Sciences. LE has received research grants from EDCTP, and Gilead Sciences. LL has received research grants from EDCTP, Gilead Sciences, Roche Diagnostic, DO has received research grants from EDCTP, AS has received research grants from EDCTP, AP has received research grants from EDCTP, PN has received research grants from EDCTP, PS has received research grants from EDCTP, DS has received research grants from EDCTP, RM has received research grants from EDCTP, BA has received research grants from EDCTP, SP has received research grants from EDCTP, CC is an employee of Gilead Sciences, JS has received research grants from EDCTP, HW has received research grants from EDCTP, SK has received research funding, speaker honoraria and consulting fees from EDCTP, Gilead Sciences, ViiV, Merck, GSK, and Ridgeback. FC has received research grants from EDCTP and Vetenskapsrådet. ELW has received grants from EDCTP, MRC, and NIH. CG has received research grants from EDCTP. PK has received research grants from EDCTP. EW has received research grants from EDCTP, NIH and MRC. NM has received research grants from EDCTP, and Gilead Sciences and provided unpaid advice and leadership in the DSMB and Setshaba boards. CC is a full-time employee of Gilead Sciences. All other authors declare no competing interests aside from the research grant received for this study by EDCTP.

Auteurs

Carolina Herrera (C)

Department of Infectious Disease, Faculty of Medicine, Imperial College London, Norfolk Place, W2 1PG, London, UK.

Jennifer Serwanga (J)

Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda.

Laura Else (L)

Department of Molecular and Clinical Pharmacology, William Henry Duncan Building, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.

Lebina Limakatso (L)

Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Africa Health Research Unit, Durban, South Africa.

Daniel Opoka (D)

Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda.

Andrew S Ssemata (AS)

Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda; Department of Global Health and Development, London School of Hygiene & Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, UK.

Azure-Dee Pillay (AD)

Division of Immunology, University of Cape Town, South Africa based at Respiratory and Meningeal Pathogens Research Unit (RMPRU). Chris Hani Baragwanath Hospital, 30 Chris Hani Road, Diepkloof, Soweto, 1862, South Africa.

Patricia Namubiru (P)

Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda.

Thabiso B Seiphetlo (TB)

Division of Immunology, University of Cape Town, South Africa based at Respiratory and Meningeal Pathogens Research Unit (RMPRU). Chris Hani Baragwanath Hospital, 30 Chris Hani Road, Diepkloof, Soweto, 1862, South Africa.

Geoffrey Odoch (G)

Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda.

Susan Mugaba (S)

Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda.

Portia Seatlholo (P)

Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Africa Health Research Unit, Durban, South Africa.

Amara Alieu (A)

Department of Molecular and Clinical Pharmacology, William Henry Duncan Building, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.

Sujan Dilly Penchala (SD)

Department of Molecular and Clinical Pharmacology, William Henry Duncan Building, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.

Richard Muhumuza (R)

Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda.

Berenice Alinde (B)

Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, Cape Town, South Africa.

Stefan Petkov (S)

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.

Kyle O'Hagan (K)

Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, Cape Town, South Africa.

Christian Callebaut (C)

Gilead Sciences, Foster City, CA 94404, USA.

Janet Seeley (J)

Department of Global Health and Development, London School of Hygiene & Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, UK; Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda.

Helen Weiss (H)

MRC International Statistics and Epidemiology Group, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Saye Khoo (S)

Department of Molecular and Clinical Pharmacology, William Henry Duncan Building, University of Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK.

Francesca Chiodi (F)

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden.

Clive M Gray (CM)

Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Biomedical Research Institute, Stellenbosch University (Tygerberg Campus), Francie van Zijl Drive, Tygerberg, Cape Town, South Africa.

Pontiano Kaleebu (P)

Medical Research Council/Uganda Virus Research Institute, and London School of Hygiene and Tropical Medicine, Uganda Research Unit, 51-59 Nakiwogo Road, Entebbe, Uganda.

Emily L Webb (EL)

MRC International Statistics and Epidemiology Group, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Neil Martinson (N)

Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Africa Health Research Unit, Durban, South Africa; Johns Hopkins University Center for TB Research, Baltimore, MD, USA.

Julie Fox (J)

Infection and Immunity, Borough Wing, Guys and St Thomas' NHS Foundation Trust and King's College London, St. Thomas Street, SE1 9RS, London, UK. Electronic address: Julie.fox@kcl.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Dose finding study for on-demand HIV...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › Dose finding study for on-demand HIV...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antirétroviraux › Agents antiVIH › Dose finding study for on-demand HIV...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Prophylaxie pré-exposition › Dose finding study for on-demand HIV...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Dose finding study for on-demand HIV...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Nucléosides pyrimidiques › Désoxycytidine › Emtricitabine › Dose finding study for on-demand HIV...
questionsmedicales.fr › Régions géographiques › Afrique › Afrique subsaharienne › Dose finding study for on-demand HIV...