Human Papillomavirus and Anorectal Immunology in HIV-positive Men who have Sex with Men
Bibliographic record
Abstract
Anal human papillomavirus (HPV) infection is prevalent among HIV-positive men who have sex with men (MSM) and can lead to the development of anal intraepithelial neoplasia (AIN) before possibly progressing to anal cancer. However, very little is known about mucosal immune changes that occur as a consequence of AIN development. As such, the overarching goal of this thesis was to explore the impact of AIN on anorectal immunology in HIV-positive MSM. Because my studies took place in Toronto, Canada, I first aimed to understand anal HPV prevalence among MSM living in Toronto. To this end, I analyzed data collected from a previous study and confirmed a high anal HPV prevalence of 82% in 294 HIV-positive and 148 HIV-negative MSM. I began my thesis work by testing whether AIN is associated with increased anorectal HIV shedding in men with suppressed HIV viremia. Although I did not find an association between AIN and anorectal HIV shedding, a subset of the cohort did have low-level anorectal HIV shedding despite effective ART. Therefore, I next assessed mucosal immune correlates of HIV shedding. Contrary to my hypothesis, mucosal inflammation was not associated with HIV shedding in ART-treated MSM. Finally, I aimed to identify immune predictors of AIN regression. I found compelling evidence to support that T cell activation within AIN lesions is associated with natural regression. Moreover, AIN regressors had significantly higher systemic responses to HPV peptides than non-regressors, and these responses in the blood strongly correlated with T cell activation in AIN lesions. Taken together, the findings presented in this thesis demonstrate that while AIN is unlikely to enhance HIV transmission in ART-treated men, differential immune responses within AIN lesions can help predict clinical outcomes. Further studies are warranted to 1) understand the relationship between HIV shedding and the HIV reservoir; and 2) inform clinical management of AIN. Importantly, if similar mucosal immune responses mediate AIN regression in HIV-negative MSM, this may be a mechanism by which anal HPV/AIN increases HIV susceptibility; thus, the association between AIN and HIV susceptibility in HIV-negative MSM should be investigated in the future.
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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 | 0.000 | 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".