CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

1066 COPPER IUD AND LEVONORGESTREL IMPLANT INCREASE GENITAL INFLAMMATION IN THE ECHO TRIAL Jennifer Deese 1 , Nina Radzey 2 , Bahiah Meyer 2 , Pai-Lien Chen 1 , Sophie Gao 1 , Charles S. Morrison 1 , Celia Mehou-Loko 2 , Florence L. D'Hellencourt 1 , Gregory Buck 3 , Jennifer Smit 4 , Jerome Strauss 3 , Kavita Nanda 1 , Khatija Ahmed 5 , Rushil Harryparsad 2 , Lindi Masson 2 1 FHI 360, Durham, NC, USA, 2 University of Cape Town, Cape Town, South Africa, 3 Virginia Commonwealth University, Richmond, VA, USA, 4 MatCH, Durban, South Africa, 5 Setshaba Research Center, Pretoria, South Africa Background: The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial found no substantial difference in HIV acquisition risk between women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or the levonorgestrel (LNG) implant. However, ECHO did not address whether these contraceptives increase HIV risk relative to other contraceptive methods or to no contraception. We investigated the impact of DMPA-IM, copper IUD and LNG implant on cervicovaginal inflammatory profiles previously associated with HIV acquisition, among a sub-cohort of ECHO participants. Methods: This study included 168 ECHO participants at the Setshaba Research Centre in Tshwane and MRU in eThekwini, South Africa. Eleven cytokines and antimicrobial peptides were measured in duplicate using Luminex in lateral vaginal wall swabs. Changes in cytokine concentrations were assessed using Wilcoxon signed rank test and generalized linear modelling. P values were adjusted for multiple comparisons using a false discovery rate procedure. Results: Baseline cervicovaginal cytokine concentrations were elevated in women with Neisseria gonorrhoeae infection and dampened among herpes simplex virus (HSV)-2 seropositive women. Younger women had higher concentrations of IL-8 and IL-1β. The copper IUD and LNG implant were associated with rapid increases in inflammatory markers following contraceptive initiation. Pro-inflammatory IL-1β and IL-6 and chemotactic IL-8, IP-10, MIP-1 ⍺ and MIP-1β were significantly elevated one month following copper IUD insertion. No changes were evident at one month post LNG implant insertion, however at three months, TNF- ⍺ , IP-10, MIP-3 ⍺ and SLPI were significantly raised relative to baseline. Significant effect modification was observed by N. gonorrhoeae and HSV-2 infection. Conclusion: The copper IUD and the LNG implant are associated with increased cervicovaginal inflammatory markers that have been linked to HIV infection risk. These effects are modified by STI status. Recent studies have demonstrated the important interplay between inflammation, the microbiome, contraception and HIV risk. Continued research to understand these effects are critical for safe contraceptive use and to inform novel contraceptive development. 1067 DOUCHING IS ASSOCIATED WITH RECTAL INFLAMMATION IN HIV- NEGATIVE SEXUAL MINORITY MEN Angela M. McGaugh 1 , Charlene Miller 1 , Justice King 1 , Kathryn McManus 1 , Maria L. Alcaide 1 , Jose Bauermeister 2 , Christian Grov 3 , Jennifer A. Manuzak 1 , Courtney Broedlow 1 , Robert Parisi 4 , Darling Martinez 4 , Nichole Klatt 1 , AdamW. Carrico 1 1 University of Miami, Miami, FL, USA, 2 University of Pennsylvania, Philadelphia, PA, USA, 3 City University of New York, New York, NY, USA, 4 AIDS Healthcare Foundation, Los Angeles, CA, USA Background: Rectal douching may increase vulnerability to HIV and other sexually transmitted infections (STIs) in sexual minority men (i.e., gay, bisexual, and other men who have sex with men). However, relatively little is known about the pathways whereby rectal douching could amplify biological vulnerability to HIV and other STIs. Methods: Participants were recruited in four STI clinics in South Florida operated by the AIDS Healthcare Foundation. Rectal swabs for 92 participants who reported engaging in condomless receptive anal intercourse (CRAI) and no antibiotic use in the past three months were selected to measure inflammatory cytokines using LEGENDplex. Multivariate logistic regression analyses examined the independent associations of rectal douching with detectable levels of rectal interleukin-6 (IL6), interleukin-8 (IL-8), and tumor necrosis factor – alpha (TNF-α). Models were adjusted for age, pre-exposure prophylaxis (PrEP) use, and number of CRAI partners in the past three months. Results: Participants were between 19 and 80 years old (mean age=34.6; SD=13.7), and 54%were ethnic minorities (37% Hispanic/Latino, 14% Black/ African American, and 3% other ethnic minority). Approximately 28% of participants were taking PrEP, 90% reported testing negative for HIV in the past year, and nearly 70% reported rectal douching. Participants who douched

reported more CRAI partners (Cohen’s d = 0.51; p < 0.01) and more instances of CRAI with ejaculation (Cohen’s d = 0.50; p = 0.03). As shown in the Figure, a significantly greater proportion of men who douched had detectable rectal IL-6 (80% versus 44%; p = 0.002) and IL-8 (69% versus 41%; p = 0.019). In adjusted analyses, douching was independently associated with more than 4-fold greater odds of detectable rectal IL-6 (adjusted odds ratio [AOR] = 4.78; 95% CI = 1.45 – 15.76) and more than 3-fold greater odds of detectable rectal IL-8 (AOR = 3.12; 95% CI = 1.06 – 9.19). Conclusion: This study is among the first to observe that rectal douching is independently associated with rectal inflammation, which was assessed using non-invasive rectal swabs. Novel behavioral and biomedical approaches that mitigate heightened rectal inflammation in sexual minority men who douche could reduce biological vulnerability to HIV or other STIs.

Poster Abstracts

1068 SEXUAL VIOLENCE EXPOSURE DYSREGULATES HIV-ASSOCIATED IMMUNE BIOMARKERS IN WOMEN Annette Aldous 1 , Jason Daniels 1 , Christopher Joy 1 , Mariel Jais 1 , Kaleigh Connors 1 , Hani Mohamed 1 , Brendan Capozzi 1 , Sam Simmens 1 , Manya Magnus 1 , Afsoon Roberts 1 , Gary Simon 1 , Mimi Ghosh 1 1 George Washington University, Washington, DC, USA Background: HIV/AIDS and sexual violence act synergistically to adversely and disproportionately impact women’s health. Yet immuno-biological mechanisms linking sexual violence and increased HIV susceptibility are incompletely understood. We aimed to determine systemic and mucosal immune dysregulation in women who had experienced recent sexual violence. Methods: We conducted a cross-sectional study of premenopausal, HIV- negative women from the Washington DC area, comparing 13 cases who had experienced forced vaginal penetration (FVP) within the past 12 weeks and 25 controls who had never experienced FVP. Clinical data as well as plasma and cervicovaginal lavage (CVL) samples were collected and ELISA assays performed to measure inflammatory, anti-inflammatory, anti-HIV, and wound healing biomarkers. We modeled differences between cases and controls using linear and logistic regression with inverse probability of treatment weighting based on age, race, insurance status, menstrual cycle phase, hormonal contraceptive use, and other contraceptive use. We used the Benjamini–Yekutieli method to control the false discovery rate (FDR) for 47 tests. Results: In CVL, cases had reduced levels of chemokines MIP-3α (p=.003) and MCP-1 (p<.001) and anti-HIV/wound-healing marker Thrombospondin-1 (TSP-1) (p=.027). Conversely, they had increased inflammatory cytokine IL-1α (p=.001) and were more likely to have detectable levels of wound-healing platelet derived growth factor (PDGF) (OR=7.89; p=.019). In plasma, cases had decreased levels of chemokines MIP-3α (p<.001) and IL-8 (p=.004), anti- inflammatory cytokine TGF-β (p=.016), anti-HIV factor beta defensin 2 (HBD2) (p=.017), and wound-healing protease MMP-1 (p=.019). They had higher levels of protease Cathepsin B (p=.010) and TSP-1 (p=.003) and were more likely to have detectable chemokine IP-10 (OR=12.24; p=.064). The associations of case status with reduced MCP 1 in CVL and reduced MIP 3α in plasma remained statistically significant at α = .05 after FDR adjustment. Conclusion: We found indications of distinct systemic and mucosal immune dysregulation in women who had experienced recent sexual violence. As some of these biomarkers have been associated with HIV infection and pathogenesis, dysregulation may increase HIV susceptibility in these women. This data informs future studies on HIV prevention in the setting of sexual violence and directs development of novel therapeutic interventions and trauma-informed care.

CROI 2020 401