Characterizing the Impact of Penile-vaginal Sex on the Immune Correlates of HIV Susceptibility in the Female and Male Genital Tracts
Bibliographic record
Abstract
Globally most HIV transmission occurs through penile-vaginal sex. Various factors in the genital tract of the uninfected partner increase the risk of HIV acquisition, including sexually transmitted infections (STIs) and the genital microbiome, with mucosal inflammation serving as the central pathway for enhanced risk. However, the clinical studies defining the mucosal immune correlates of HIV susceptibility collected genital samples remote from sexual activity, while HIV penetrates mucosal tissues within hours of sex. Therefore, it is critical to understand the impact of penile-vaginal sex itself on genital immunology. This was the primary objective of the Sex, Couples and Science study (SECS) project. Cervical cytobrush sampling is commonly used to study immune cell populations in the FGT, but the impact of sample collection itself on mucosal immunology has not been defined. Therefore, I first investigated the impact of cytobrush sampling on mucosal correlates of HIV susceptibility after 6 and 48 hours. Cytobrush sampling increased cervical HIV target cell numbers and pro-inflammatory cytokine levels at 6 hours, with most immune changes resolving by 48 hours. Cytobrush sampling did not alter the absolute abundance of key vaginal bacteria. Therefore, in designing the SECS protocol I ensured that there was a gap of at least 48 hours between consecutive cytobrush samples. I then recruited 40 established heterosexual couples to assess the impact of penile-vaginal sex, either condomless or condom-protected, on FGT and penile immunology. The level of penile and cervico-vaginal cytokines previously associated with HIV acquisition increased 1 hour after sex, regardless of condom use, and returned to baseline levels by 72 hours. Penile cytokine changes largely reflected exposure to cytokine-rich FGT secretions. The proportion of endocervical HIV target cells, specifically Th17 cells and activated/mature dendritic cells (DCs), increased transiently 1 hour after condomless sex, although this increase was only seen in the context of an uncircumcised male partner. In summary, penile-vaginal sex induced profound short-term immune changes that may enhance HIV susceptibility in women and men. This furthers our understanding of the biology of mucosal HIV acquisition and has implications for the design of clinical studies assessing mucosal immunology and HIV acquisition.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".