Initiating Intramuscular Depot Medroxyprogesterone Acetate Increases Frequencies of Th17-like Human Immunodeficiency Virus Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial. (9th August 2022)

• Record Type: Journal Article
• Authors: Bunjun, Rubina; Ramla, Tanko F; Jaumdally, Shameem Z; Noël-Romas, Laura; Ayele, Hossaena; Brown, Bryan P; Gamieldien, Hoyam; Harryparsad, Rushil; Dabee, Smritee; Nair, Gonasagrie; Onono, Maricianah; Palanee-Phillips, Thesla; Scoville, Catilin W; Heller, Kate B; Baeten, Jared M; Bosinger, Steven E; Burgener, Adam; Passmore, Jo-Ann S; Jaspan, Heather; Heffron, Renee
• Is Part Of: Clinical infectious diseases. Volume 75:Number 11(2022)
• Page Start: 2000
• Page End: 2011
• Publication Date: 2022-08-09
• Subjects: hormonal contraception -- HIV risk -- Th17 cells -- mucosal barrier integrity; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciac284
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Cervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells. Methods: Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry. Results: Unlike the LNG implant or copper-IUD, DMPA-IM was associated with higher frequencies of cervical Th17-like cells within 1 month of initiation ( P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and α4β7 ( P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD ( P = .0002) or LNG implant ( P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non– Lactobacillus- dominant microbiome at baseline was associated with more Th17-like cells post–DMPA-IM ( P = .03), although this did not influence barrier function. Conclusions: Our data suggest that DMPA-IM–driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity. Clinical Trials Registration: NCT02550067. Abstract : Cervicovaginal Th17-like cells significantly increased in women after initiation of DMPA-IM but not the Cu-IUD or LNG-implant. Proteomic analyses suggest that this DMPA-driven accumulation of HIV susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity.