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

• Published in: Clinical infectious diseases Vol. 75; no. 11; pp. 2000 - 2011
• Main 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
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 30.11.2022
• Subjects: Contraceptive Agents, Female - pharmacology; Copper; Disease Susceptibility; Female; HIV; HIV Infections - epidemiology; Humans; Levonorgestrel; Major; Medicin och hälsovetenskap; Medroxyprogesterone Acetate - pharmacology; Proteomics; South Africa; Vagina; South Africa; hormonal contraception; mucosal barrier integrity; HIV risk; Th17 cells
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciac284

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. 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. 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. 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. NCT02550067.