CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: A strong interaction between BV and hormonal contraceptives as mediators of women’s HIV risk, if present, would be an important and potentially actionable finding. However, significant interaction was not observed in this cohort. Analyses of hormonal contraceptive and BV data from diverse HIV incidence cohorts will help to clarify this important question. 1000 CHANGES IN VAGINAL MICROBIOTA AMONG HIV-INFECTED AFRICAN WOMEN INITIATING DMPA Bridget M. Whitney 1 , Ken Tapia 1 , Sujatha Srinivasan 2 , Eric M. Muriuki 3 , Bhavna Chohan 1 , Jacqueline Wallis 2 , Congzhou Liu 2 , R. Scott McClelland 1 , Noah G. Hoffman 1 , David N. Fredricks 2 , Alison C. Roxby 1 1 University of Washington, Seattle, WA, USA, 2 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 3 University of Nairobi, Nairobi, Kenya Background: Depot-medroxyprogesterone acetate (DMPA) has been linked to HIV acquisition, and limited evidence also exists linking DMPA with higher risk of HIV transmission. The biological mechanism underlying these associations is not well understood. DMPA use has been documented to reduce bacterial vaginosis (BV), but there are fewmolecular studies assessing how DMPA alters vaginal microbiota. We hypothesized that a possible mechanism by which DMPA could increase HIV transmission would be to increase vaginal bacteria diversity. Methods: We conducted a cohort study of postpartum, breastfeeding women in Kenya initiating DMPA or non-hormonal contraception (NHC). Women received their first DMPA injection or condoms at enrollment and were followed longitudinally. Vaginal Gram stains were assessed to calculate Nugent score. Vaginal swabs were analyzed with broad-range 16S rRNA gene PCR and sequencing to assess bacterial diversity using Shannon Diversity Index (SDI). Adjusted linear mixed-effects regression was used to estimate mean changes in Nugent score, SDI, and vaginal pH over time in women using DMPA compared to those using NHC. Results: We enrolled 66 HIV-infected women, 50 initiating DMPA and 16 choosing NHC. At baseline, a greater proportion of DMPA users were married and had resumed sexual activity. Mean Nugent score, mean SDI, and mean vaginal pH were similar at baseline (Table). Over 3 months, Nugent score did not significantly change in DMPA users (Δ=-0.71; p=0.51), and this change was not significantly different from the change seen in NHC users (diff.=1.43; p=0.46). Mean SDI also did not change over time in DMPA users (Δ=-0.32, p=0.23), and again, this change was not significantly different from the change in NHC users (diff.=0.46, p=0.29). Lastly, vaginal pH decreased significantly over time in DMPA users (Δ=-0.64; p=0.01), however the change was not significantly different from the change in NHC users (diff.=-0.05; p=0.94). Conclusion: In a cohort of African women, 3 months of DMPA use was not associated with acute, significant changes to vaginal bacterial diversity. Further, DMPA users did not have significantly different Nugent scores or greater vaginal bacterial diversity compared to NHC users. This finding suggests that change in vaginal bacterial diversity is not a main driver of increased risk of HIV transmission among DMPA users. Additional analyses of taxon-specific data will help determine if DMPA causes changes to specific vaginal microbiota which could explain this association.

1 Albert Einstein College of Medicine, Bronx, NY, USA, 2 New York University, New York City, NY, USA, 3 New York Medical College, Valhalla, NY, USA, 4 Rutgers University, Piscataway, NJ, USA, 5 Maimonides Medical Center, Brooklyn, NY, USA Background: Reproductive aging may affect the vaginal microbiome, mucosal immune environment and genital tract health in HIV-infected (HIV+) women. Methods: A cross-sectional study of 102 HIV+ (51 premenopausal, 51 postmenopausal) and 39 HIV-uninfected (HIV-) (20 premenopausal, 19 postmenopausal) women was conducted in Bronx and Brooklyn, NY. Cervicovaginal lavage (CVL) was collected in 10 ml sterile water for quantification of innate antimicrobial activity against E. coli, HSV-2 and HIV and soluble immune mediators by Luminex and ELISA. Vaginal swabs were obtained for microbiome studies utilizing qPCR and 16S rRNA sequencing. Results: HIV+ postmenopausal participants had significantly lower median E. coli inhibition, lower median gene copies of L. crispatus and L. iners, and lower mean log10 concentrations of human beta defensins (HBD-2, HBD-3) and secretory leukocyte protease inhibitor (SLPI) compared to HIV+ premenopausal women. In relation to premenopausal, HIV+ postmenopausal participants showed significantly higher proportions of Gardnerella and Atopobium vaginae and lower proportions of Lactobacillus sp. In contrast, HSV-2 inhibitory activity was higher in HIV+ postmenopausal women and correlated with the proinflammatory molecules interleukin (IL) 6, IL-8, human neutrophil peptide (HNP) 1-3, lactoferrin and fibronectin. The HIV inhibitory activity was variable, but higher in participants with suppressed plasma viral load, and inversely correlated with G. vaginalis and BVAB2. A significant proportion of HIV+ participants on antiretroviral therapy exhibited HIV enhancing activity. Similar trends were observed in HIV- postmenopausal compared to premenopausal participants. Conclusion: HIV+ postmenopausal compared to premenopausal women have less CVL E. coli inhibitory activity, reflecting a lower proportion of lactobacilli species and a greater proportion of Gardnerella and A. vaginae, and more HSV-2 inhibitory activity, reflecting increased mucosal inflammation. The effect of menopause on mucosal immunity was greater in HIV+ than in HIV- participants, suggesting a synergistic impact. It is possible that promotion of a lactobacillus dominant vaginal microbiome and reduced mucosal inflammation in HIV+ menopausal women may improve vaginal health and reduce risk for shedding of HIV and potential for HIV transmission. Caitlyn L. Jasumback 1 , Sarah Perry 2 , Martha Matsenjwa 1 , Zandile T. Masangane 3 , Mpumelelo Mavimbela 3 , Anna Mandalakas 2 , Alexander Kay 2 1 Baylor College of Medicine Children’s Foundation, Mbabane, Swaziland, 2 Baylor College of Medicine, Houston, TX, USA, 3 Ministry of Health, Mbabane, Swaziland Background: Sexually transmitted infections (STIs) are a key global health problem, contributing to infertility, cancer and HIV transmission. The WHO estimates 131 million cases of chlamydia (CT) and 78 million of gonorrhea (NG) among 15-49 year olds worldwide. There is no current prevalence data on STIs in adolescents living with or without HIV in Eswatini. Methods: A cross-sectional study was done at Baylor Clinic in Mbabane, Eswatini. HIV positive participants, 15-24 years of age, were recruited serially. Participants completed a sexual health history and provided a urine sample. A subset of sexually active participants provided a pharayngeal swab and/or vaginal swab. Urinalysis (UA) was done on all urine samples. 299 samples were tested with the Xpert CT/NG test as per manufacturer guidelines. Statistical analysis included odds ratios and diagnostic performance tests. Results: 300 participants were enrolled, 141 males and 159 females. The prevalence of CT and/or NG was highest in 20-24 year old females at 15.7% (Table 1). Of ever sexually active participants (ESAP), 12.4% (20/161) were positive for CT and/or NG vs. 0.7% (1/138) reporting no prior sexual activity. Urine sample results were 100% (38/38) concordant with vaginal swab results. STI type was 57.1% (12/21) NG, 28.6% (6/21) CT and 14.3% (3/21) CT and NG. Leukocyte esterase (LE) testing from UA in ESAP had a sensitivity of 85.0% (Male [M]: 100.0%, Female [F]: 80.0%), and specificity of 64.3% (M: 83.6%, F: 51.8%). Syndromic screening alone in ESAP had a sensitivity of 25.0% (M: 80.0%, F: 6.7%) and specificity of 88.7% (M: 88.8%. F: 84.9%). Risk factors associated with STIs in ESAP were sometimes to never using condoms (OR=3.1, 95%CI=1.1-9.2), sexually active in the past 6 months (7.2, 2.4-25.7), and most recent sexual partner 25 years or older (3.2, 1.1-9.5). Among ever sexually active women, the

Poster Abstracts

1002 PREVALENCE OF CHLAMYDIA AND GONORRHEA IN HIV-POSITIVE ADOLESCENTS IN ESWATINI

1001 MENOPAUSE IMPACTS THE VAGINAL MICROBIOME AND IMMUNE MEDIATORS IN WOMEN WITH HIV

Kerry Murphy 1 , Marla J. Keller 1 , Kathryn Anastos 1 , Shada Sinclair 1 , J. C. Devlin 2 , Qiuhu Shi 3 , Donald R. Hoover 4 , Brian Starkman 1 , Jaime McGillick 1 , Caroline Mullis 3 , Howard Minkoff 5 , Maria Gloria Dominguez-Bello 2 , Betsy Herold 1

CROI 2019 392