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
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".