Human Papillomavirus and Anorectal Immunology in HIV-positive Men who have Sex with Men

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.

Department dc:contributor.department

Immunology

Year dc:date.issued

2021

Author dc:creator

• Choi, Yoojin

Advisor dc:contributor.advisor

• Kaul, Rupert

Statement dc:rights

• Attribution-NonCommercial-NoDerivatives 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/108943

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/108943