A randomized clinical trial of on-demand oral pre-exposure prophylaxis does not modulate lymphoid/myeloid HIV target cell density in the foreskin

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Rametse, Cosnet L, Webb, Emily, Herrera, Carolina, Alinde, Berenice, Besethi, Asiphe, Motaung, Bongani, Mbangiwa, Tshepiso, Leach, Lloyd, Sebaa, Shorok, Pillay, Azure-Dee APB et al (show 17 more authors) , Seiphetlo, Thabiso, Malhangu, Boitshoko, Petkov, Stefan, Else, Laura, Mugaba, Susan, Namubiru, Patricia, Odoch, Geoffrey, Opoka, Daniel, Serwanga, Jennifer S, Ssemata, Andrew, Kaleebu, Pontiano, Khoo, Saye ORCID: 0000-0002-2769-0967, Lebina, Limakatso, Martinson, Neil, Chiodi, Francesca, Fox, Julie M and Gray, Clive (2023) A randomized clinical trial of on-demand oral pre-exposure prophylaxis does not modulate lymphoid/myeloid HIV target cell density in the foreskin AIDS, 37 (11). pp. 1651-1659. ISSN 0269-9370, 1473-5571

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Abstract

Objectives:As topical pre-exposure prophylaxis (PrEP) has been shown to cause immune modulation in rectal or cervical tissue, our aim was to examine the impact of oral PrEP on lymphoid and myeloid changes in the foreskin in response to dosing and timing of drug administration.Design:HIV-negative male individuals (n = 144) were recruited in South Africa and Uganda into an open-label randomized controlled trial in a 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 ratio to control arm (with no PrEP) or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) at one of two different doses, 5 or 21 h before undergoing voluntary medical male circumcision (VMMC).Methods:After dorsal-slit circumcision, foreskin tissue sections were embedded into Optimal Cutting Temperature media and analysed, blinded to trial allocation, to determine numbers of CD4⁺CCR5⁺, CD1a⁺cells and claudin-1 expression. Cell densities were correlated with tissue-bound drug metabolites and p24 production after ex-vivo foreskin challenge with HIV-1^bal.Results:There was no significant difference in CD4⁺CCR5⁺or CD1a⁺cell numbers in foreskins between treatment arms compared with the control arm. Claudin-1 expression was 34% higher (P = 0.003) in foreskin tissue from participants receiving PrEP relative to controls, but was no longer statistically significant after controlling for multiple comparisons. There was neither correlation of CD4⁺CCR5⁺, CD1a⁺cell numbers, or claudin-1 expression with tissue-bound drug metabolites, nor with p24 production after ex-vivo viral challenge.Conclusion:Oral doses and timing of on-demand PrEP and in-situ drug metabolite levels in tissue have no effect on numbers or anatomical location of lymphoid or myeloid HIV target cells in foreskin tissue.

Item Type:	Article
Uncontrolled Keywords:	claudin-1, emtricitabine-tenofovir alafenamide, emtricitabine-tenofovir disoproxil fumarate, foreskin, HIV target cells, pre-exposure prophylaxis, voluntary medical male circumcision
Depositing User:	Symplectic Admin
Date Deposited:	19 Aug 2024 14:51
Last Modified:	16 Jun 2026 05:01
DOI:	10.1097/QAD.0000000000003619
Open Access URL:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11175...
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3183890
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