Abstract
BackgroundCervicovaginal 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 as sociated 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 D MPA-IM–driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity.
