CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

bacterial abundance (median 27,100 vs. 1,200, gene copies/swab, p=0.001). Anaerobes made up 49% of inner foreskin bacteria, but only 26% of urethral bacteria. PC did not alter urethral IL-8 (median 1058 vs. 818 pg/ml at 12 months and baseline, respectively; p=0.057) or other chemokines/ cytokines, and urethral E-cadherin increased (155,750 vs. 111,928 pg/ml, p=0.012) suggesting reduced epithelial integrity; urethral total bacterial abundance and anaerobe abundance dropped by 5-fold and 7-fold, respectively. In contrast at the CS, where there were dramatic reductions in E-cadherin (900 vs. 15,843 pg/ml, p<0.001) and most proinflammatory chemokines/cytokines (eg: IL-8, 3 vs. 34 pg/ml; p<0.001). IL-1a was increased post-PC at the CS coupled with a 14-fold reduction in total bacterial abundance (p=0.004) and 200-fold reduction in anaerobes (p<0.001). Conclusion: PC had no impact on urethral immunology and may have reduced epithelial integrity despite some reductions in total bacterial load and anaerobes; in the CS there was enhanced epithelial integrity, near total loss of anaerobes and dramatic immune alterations. This suggests that HIV protection post-PC is mediated through removal of inflamed, HIV-susceptible inner foreskin tissues rather than via the urethra. Cosnet L. Rametse 1 , Micheal Mndini 1 , Sibulelo Mollie 1 , Kyle O'hagan 1 , Nyaradzo T. Chigorimbo-Tsikiwa 1 , Gianguido C. Cianci 2 , Thomas Hope 2 , Clive M. Gray 1 1 University of Cape Town, Cape Town, South Africa, 2 Northwestern University, Chicago, IL, USA Background: The male foreskin is the main site of HIV entry in heterosexual men as evidenced by the effective protection incurred upon its removal following voluntary medical male circumcision (VMMC). However, the biological mechanism by which circumcision confers this protection remains poorly understood. To understand changes to skin barrier function after VMMC, we measured transepithelial water loss (TEWL) and hydration status in the glans, foreskin and shaft before and after (glans & shaft only) VMMC as in vivo measures for skin barrier integrity. The lower TEWL and higher hydration status equates with more intact skin barrier integrity. Methods: Hand-held vapometers and moisture meters SC & D, designed to measure water loss and content in the skin (and used extensively in dermatology and the cosmetic industry), were used to quantify TEWL (n=45 adult males), surface hydration in the stratum corneum and water content in the skin (n=31 adults) of the glans, inner foreskin and penile shaft before VMMC. These in vivo proxy measurements for skin integrity were then made two weeks after circumcision. First-pass urine samples were tested for common curable sexually transmitted infections (STIs): Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis & Mycoplasma genitalium. Results: To date, we show that 20-25%men have an asymptomatic STI. In males who were STI negative prior to circumcision, the inner foreskin and glans had higher TEWL readings compared to the shaft, whereas the surface hydration and water content were the same across all anatomical sites. Two weeks after circumcision, the TEWL readings in the glans significantly decreased (from a median of 27.6 to 17 g/hr/m 2 ) to match the shaft readings and the hydration content also decreased in all three sites but especially surface hydration in the shaft (from a median of 48 to 28 au, p=0,0061). Comparing men who were STI positive (n=9) versus STI negative at the time of VMMC, there was lower TEWL in the glans in the presence of an STI (median of 26 vs 9 g/hr/m 2 , p=0,033), but no differences in the hydration status. Conclusion: Our data show that prior to VMMC, the inner foreskin and glans had lower skin barrier integrity which increased soon after circumcision in STI negative males, but not in those with an asymptomatic STI. This finding has implications for understanding how MMC disciplines penile tissue and gives insight into how HIV acquisition may be prevented after circumcision. 213 CONDOMLESS RECEPTIVE ANAL INTERCOURSE IS ASSOCIATED WITH MARKERS OF MUCOSAL INJURY Colleen F. Kelley 1 , Rama R. Amara 2 , Veronika Fedirko 2 , Yijuan Hu 2 , Ilana Pollack 2 , Rami Yacoub 2 , Zhengyi Zhu 2 , Roberd Bostick 2 1 Emory Center for AIDS Research, Atlanta, GA, USA, 2 Emory University, Atlanta, : GA, USA Background: We previously found a unique rectal mucosal (RM) immune environment among men who have sex with men (MSM) engaging in condomless receptive anal intercourse (CRAI) typified by a pro-inflammatory 212 MEDICAL MALE CIRCUMCISION DISCIPLINES THE PENIS: UNDERSTANDING HIV SUSCEPTIBILITY

response to CRAI and a microbiota enriched for Prevotellaceae over Bacteroidaceae. Further exploration of the RM immune environment among MSM engaging in CRAI will lead to a better understanding of HIV transmission. Methods: To investigate expression of MPO (neutrophils), IL-17 (inflammatory cells), and FOXP3 (immunosuppressive cells) in the lamina propria and Ki67 (proliferating cells) and e-cadherin (tight junctions) in the crypt epithelium of RM, we used standardized, automated immunohistochemistry and quantitative image analysis in a cohort of 41 MSM engaging in CRAI and 21 men who had never engaged in CRAI (controls) over 2 study visits. The RMmicrobiota was characterized with 16s rRNA sequencing. Linear mixed effects models were used to examine differences in biomarker expression between study groups over time. A linear decomposition model (LDM) was constructed to examine associations between the biomarkers and microbiota. Results: Expression of cellular markers MPO, IL-17, and FOXP3 increased from the base of the crypt towards the lumen of the RM; while Ki-67 and e-cadherin decreased (Figure). After adjustment for race and age in mixed effects models, among MSM engaging in CRAI relative to controls, the expression of MPO in the lamina propria and Ki67 in the epitheliumwere 41% (p<0.05) and 60% (p=0.03) higher, respectively. There were no significant differences in the other 3 biomarkers or in biomarker expression among MSM engaging in CRAI based on timing of sexual intercourse. No significant associations were detected between the 5 biomarkers and global composition of the RMmicrobiota or individual taxa examined, including Bacteroides and Prevotella genera. Conclusion: Increased infiltration of neutrophils and proliferation of crypt epithelial cells in the RM of MSM likely represent an injury response to frequent CRAI, which could facilitate HIV transmission through increased inflammation. However, the role of the microbiota in contributing to RM inflammation among MSM remains unclear. Prevention interventions that reduce RM inflammation or that capitalize on the presence of a specific inflammatory mechanism (e.g. neutrophil response) at the time of HIV exposure in the RM could enhance efficacy.

Poster Abstracts

214 IMMUNE CORRELATES OF ANORECTAL HIV SHEDDING IN MEN ON ANTIRETROVIRAL THERAPY Yoojin Choi 1 , Irving Salit 2 , Sarah Grech 1 , Marie Sano 2 , Edward Weiss 2 , Rupert Kaul 1 1 University of Toronto, Toronto, ON, Canada, 2 University Health Network, Toronto, ON, Canada Background: Antiretroviral therapy (ART) effectively suppresses HIV levels in plasma. While HIV levels at mucosal surfaces generally also fall to undetectable levels, several groups have described detectable HIV shedding in the anogenital tissues of ART-treated individuals, and the immune correlates of HIV shedding in the context of effective ART are not well understood. Because mucosal inflammation drives increased HIV shedding in ART-naïve individuals, we hypothesized that anorectal HIV shedding in ART-treated men would be associated with activated mucosal CD4+ T cells. Methods: Fifty-four HIV-infected, ART-treated men who have sex with men were recruited from Toronto, Canada. Anal swabs were used to test for HIV RNA levels by RT-PCR. High-resolution anoscopy was performed to collect anal biopsies, and lymphocytes isolated from collagenase-treated biopsies were stained for flow cytometric analysis. Markers included: CD38/HLA-DR (immune

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CROI 2020