CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

239 PENILE BACTERIAL SPECIES ASSOCIATED WITH INCREASED HIV RISK IN HETEROSEXUAL MEN Maliha Aziz 1 , Zoe Packman 2 , Jessica Prodger 3 , Ronald M. Galiwango 4 , Alison Abraham 2 , Fred Nalugoda 5 , Sanjeev Sariya 1 , Lance Price 1 , Godfrey Kigozi 5 , Aaron Tobian 2 , Rupert Kaul 4 , Ronald H. Gray 6 , Cindy M. Liu 1 1 George Washington University, Washington, DC, USA, 2 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 3 Western University, London, ON, Canada, 4 University of Toronto, Toronto, ON, Canada, 5 Rakai Health Sciences Program, Kalisizo, Uganda, 6 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: Anaerobic genera that are decreased in abundance after male circumcision have been associated with increased risk for HIV seroconversion. It is hypothesized that only a subset of species within these genera are specifically associated with HIV risk, but they have yet to be identified. Additional penile bacteria that remain abundant after male circumcision could also play a role, which may explain the residual HIV risk after male circumcision. Identifying such novel bacteria requires a broad, discovery-based study of penile bacterial species and associations with HIV acquisition risk. Methods: We conducted a case-control study of uncircumcised men enrolled in a randomized trial of male circumcision in Rakai, Uganda. Cases (n=68) were men who acquired HIV during the 24-month follow-up and controls (n=199) were persistently HIV-uninfected men. Cases and controls were matched by randomization arm. Using DNA extracted from eluent of sub-preputial swabs, bacterial absolute abundance was estimated by pan-bacterial real-time PCR and sequencing of the 16S rRNA V3V6 region. Species-level classification was performed using a custom in-house Bayesian Classifier. Logistic regression was used to assess the adjusted odds ratio (adjOR) of HIV seroconversion associated with anaerobe abundance. Using a step-wise approach, genera, and subsequently species associated with HIV seroconversion were identified if they met three of four following criteria: a) above 1st quantile in absolute abundance, b) indicator value > 0.7 from indicator analysis, c) significant univariate association with seroconversion, and d) a priori evidence of association with seroconversion (genera only). Results: We identified 14 penile genera associated with increased seroconversion risk, which included nine of the 10 anaerobic genera reduced by male circumcision, plus Atopobium, Gardnerella, Lactobacillus, Parvimonas, and Sneathia. Analyses using species-level data from the 14 genera identified 21 penile bacterial species associated with increased HIV risk (Table 1). Each 10-fold increase of penile bacterial species was associated with 22-57% increase in the odds of seroconversion after adjusting for known HIV risk factors. Conclusion: This open-ended analysis demonstrated that men acquiring HIV had a higher density of anaerobic penile bacteria and a higher density of bacteria associated with vaginal inflammation (G. vaginalis) and health (L. crispatus).

Poster Abstracts

240 FORESKIN HIV TARGET CELLS AND PENILE ANAEROBES ASSOCIATED WITH HIV SEROCONVERSION Jessica Prodger 1 , Zoe Packman 2 , Ronald M. Galiwango 3 , Alison Abraham 2 , Fred Nalugoda 4 , Maliha Aziz 5 , Sanjeev Sariya 5 , Kelsey Roach 5 , Lance Price 5 , Godfrey Kigozi 4 , Ronald H. Gray 6 , Aaron Tobian 2 , Rupert Kaul 3 , Cindy M. Liu 5 1 Western University, London, ON, Canada, 2 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 3 University of Toronto, Toronto, ON, Canada, 4 Rakai Health Sciences Program, Kalisizo, Uganda, 5 George Washington University, Washington, DC, USA, 6 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: Inflammation has been associated with risk for HIV seroconversion. Specific penile anaerobes may increase HIV risk in men by triggering a cascade of soluble pro-inflammatory factors, such as IL-8, resulting in the recruitment of CD4+ cells to the foreskin. To test this hypothesis, we evaluated the association between abundance of penile anaerobes with sub- preputial soluble immune factors and target cells. Methods: We conducted a cross-sectional study of 88 HIV-negative heterosexual uncircumcised men from the Rakai Community Cohort Study in Uganda. Sub-preputial swabs and foreskin tissues were collected. Using DNA extracted from sub-preputial swab eluent, we estimated absolute abundance of 21 penile bacterial species associated with seroconversion as the log10 16S rRNA gene copies/swab by pan-bacterial real-time PCR and sequencing of the 16S rRNA V3V6 region. Four negative control genera-Corynebacterium, Staphylococcus, Helcococcus, and Negativiococcus were also included in the analysis. We measured IL-8 concentration using multiplex mesoscale discovery platform analyzed foreskin tissue for immune cell density by immunohistochemistry and flow cytometry. We assessed association between abundance of penile anaerobes with sub-preputial IL-8 and foreskin total CD4+ (log10) T-cell densities by rank-based metrics: Spearman’s correlation and quantile regression. Results: Abundance of all 21 seroconversion-associated penile bacterial species correlated significantly with sub-preputial IL-8 (Spearman Rho range: 0.25- 0.60; p < 0.05) while none of the negative control bacteria were significantly associated with IL-8. However, only seven species from three genera (Peptostreptococcus, Dialister, Prevotella) were correlated and associated significantly with increased CD4+ T-cell density (Table 1). The four negative control bacteria were not associated with sub-preputial IL-8 or foreskin immune cell density (Table 1).

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CROI 2019