CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

268 VAGINAL MICROBIOTA AND HIV ACQUISITION RISK AMONG AFRICAN WOMEN Sujatha Srinivasan 1 , Barbra A. Richardson 2 , Jacqueline Wallis 1 , Tina L. Fiedler 1 , Charlene S. Dezzutti 3 , Z. Mike Chirenje 4 , Edward W. Livant 5 , David N. Fredricks 1 , Sharon L. Hillier 3 , Jeanne Marrazzo 6 1 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 2 University of Washington, Seattle, WA, USA, 3 University of Pittsburgh, Pittsburgh, PA, USA, 4 University of Zimbabwe, Harare, Zimbabwe, 5 Magee–Womens Research Institute, Pittsburgh, PA, USA, 6 University of Alabama at Birmingham, Birmingham, AL, USA Background: Recent studies have identified vaginal bacterial community types and species associated with HIV acquisition risk. However, results have not been consistent, perhaps reflecting different study populations and methods. We aimed to define associations between concentrations of vaginal bacterial species and genera with risk of HIV acquisition among women participating in the VOICE study, a randomized placebo-controlled trial of daily oral vs. vaginal tenofovir-based pre-exposure prophylaxis for HIV. Methods: Vaginal swabs were collected routinely at 6 month intervals or when pelvic examination was indicated. Cases and controls were matched by study arm and site. Concentrations of nine bacterial taxa previously shown to be associated with increased HIV risk, and one associated with protection, were measured using quantitative PCR. Each taxon was analyzed as a four-category exposure including undetectable, 1 st , 2 nd , and 3 rd tertiles of concentrations, and relationship between bacterial concentrations and HIV risk assessed using Generalized Estimating Equation models. A Benjamini-Hochberg False Discovery Rate of 0.05 was applied. Models were adjusted for age, contraception method, number of sex partners, frequency of sex, and report of condom use. Results: The relationship between vaginal bacteria and HIV acquisition at 177 HIV pre-seroconversion visits from 150 women who acquired HIV (cases), and 531 visits from 436 women who remained HIV uninfected (controls) was examined. Six taxa were significantly associated with increased HIV acquisition including Eggerthella sp. Type 1 (p=0.011), Gemella asaccharolytica (p=0.002), Leptotrichia/Sneathia spp. (p=0.021), Megasphaera sp. Type 2 (p<0.001), Mycoplasma hominis (p<0.001), and Parvimonas sp. Type 2 (p=0.01). Prevotella bivia , previously linked with higher risk in South African women, was not significant in the adjusted model (p=0.055). Megasphaera sp. Type 1 (p=0.66) and Parvimonas sp. Type 1 (p=0.16) were not associated with increased risk. Women with the highest tertiles of Lactobacillus crispatus had a decreased risk of HIV acquisition (p=0.034). Conclusion: Concentrations of specific vaginal bacteria are consistently associated with HIV acquisition risk in African women. Bacterial targets may serve as biomarkers of HIV risk or protection. Antibacterial therapy could be explored as one approach to reduce HIV risk in women. 269 THE VAGINAL MICROBIOME IN PREGNANCY DIFFERS BY HIV STATUS, ART EXPOSURE, AND CLASS Charlotte-Eve S. Short , Richard Brown, Rachael A. Quinlan, Robin J. Shattock, Phillip R. Bennett, Graham P. Taylor, David A. MacIntyre Imperial College London, London, UK Background: The vaginal microbiome during healthy pregnancy is characterised by increased Lactobacillus spp. dominance and reduced diversity. Increased diversity or early dominance by Lactobacillus iners associates with preterm birth (PTB) risk. The composition of vaginal bacterial communities in HIV–infected pregnant women is yet to be described despite their increased risk of PTB. This study characterises and compares the vaginal microbiome of HIV- infected pregnant women with uninfected pregnant women delivering at term, and explores associations with PTB and antiretroviral therapy (ART). Methods: Pregnant women were prospectively recruited from 10 London antenatal clinics to 2 cohorts: HIV-infected with a CD4 cell count >350 cells/ mL (n=53) and uninfected controls (n=30). HIV infected women were further classified as pre ART (no therapy(12)), on PI–based ART(16) and non PI-based ART(25). High vaginal swabs were obtained at 14-22 weeks. MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the microbiome. Multivariate modelling was performed to explore associations with bacterial genus/species and clinical data. Results: HIV-infected mothers (median age 35yrs), 81%were of Black ethnicity and 14% had PTB. In contrast 50% of controls were Caucasian (median age 33yrs). HIV infection was associated with higher frequency of vaginal microbial dominance by L. iners (45 v 23%, p<0.001) and G. vaginalis (17 v 7%, p<0.001), whereas L. crispatus dominance was associated with healthy controls (45 v 15%,

p<0.001). HIV-infected mothers delivering at term had higher mean abundance of Gardnerella (18 v 3%, p=0.003) and Prevotella species (4 v 0.1%, p=0.002) and lower levels of Lactobacillus species (70 v 93%, p=0.009) compared to uninfected controls. Amongst HIV-infected women, PTB was associated with increased G. vaginalis (p=0.04) and Prevotella species (p=0.05) compared with term births. Women conceiving on ART had a higher abundance of Atopobium vaginae, Snaethia and Ureaplasma parvum than women pre ART initiation (p <0.05). Women receiving PI-based ART had a higher abundance of U. parvum than women pre ART (p=0.02), not withstanding correction. No difference was observed by non PI ART or nucleoside backbone. Conclusion: Vaginal bacterial communities of HIV-infected pregnant women are characterised by increased dominance by L. iners and G. vaginalis. The associations of higher abundance of anaerobic pathogens observed with HIV, PTB and PI-exposure at conception warrant further investigation. 270 BACTERIAL VAGINOSIS ASSOCIATED MICROBES INDUCE ALTERED INNATE IMMUNE PROFILES Ryan Cheu 1 , Tiffany Hensley-McBain 1 , Avid Mohammadi 2 , Jennifer A. Manuzak 1 , Alexander S. Zevin 1 , Charlene J. Miller 1 , Mark Yudin 2 , Rupert Kaul 2 , Nichole Klatt 1 1 University of Washington, Seattle, WA, USA, 2 University of Toronto, Toronto, ON, Canada Background: Bacterial vaginosis (BV) is associated with inflammatory responses and an increased transmission rate of HIV, however, the mechanism(s) underlying this are unknown. BV is characterized by a change from a predominantly Lactobacillus spp. environment to a more diverse community, including Gardnerella vaginalis. Inflammatory cells such as neutrophils are critical for innate immune responses, but can also contribute to barrier damage and inflammation. Currently, the role of neutrophils in HIV transmission and BV status is unknown. Here, we hypothesize that BV-associated bacteria will induce neutrophil activation and prolonged life, promoting neutrophil accumulation in the female reproductive tract (FRT), thereby potentially promoting tissue damage. Methods: In order to elucidate the mechanisms for the negative consequences of BV, we collected cervicovaginal cytobrushes from 6 women with BV (Nugent >7), and without BV (Nugent <5). We used flow cytometry to assess phenotype and functionality of neutrophils, and performed in vitro whole blood co-cultures with bacteria associated with BV ( G. vaginalis ), healthy commensals such as L. iners and L. crispatus , media alone (negative control) and lipopolysaccharide and peptidoglycan (positive controls). Results: We demonstrated increased neutrophil activation via CD62L downregulation (p=0.0022) and prolonged lifespan via decreased caspase-3 expression (p=0.0022) in the cytobrushes with women with BV. Similarly, in our co-culture experiments we observed more neutrophil activation (p<0.0001) and prolonged lifespan (p=0.079) in cultures with G. vaginalis similar to our positive controls. Of interest, women without BV had reduced inflammatory immune responses similar to our in vitro experiments with cultures containing Lactobacillus spp. that maintained immune cell phenotypes similar to negative controls. Conclusion: Here, we demonstrate that BV-associated bacteria induce neutrophil activation and delay apoptosis as a potential mechanism for promoting tissue damage. Women without BV, that have healthy vaginal mucosal bacterial communities (Lactobacillus) may support the balance between antimicrobial function of neutrophils and do not induce inflammation, whereas women with BV and dysbiotic vaginal communities (G. vaginalis) potentially lead to neutrophil accumulation and tissue damage. Thus, this study provides potential mechanistic insights into how BV may lead to FRT inflammation and increased HIV transmission. 271 MICROBIOME-ASSOCIATED EPITHELIAL DISRUPTION MODIFIES HIV ACQUISITION RISK IN WOMEN Laura Noël-Romas 1 , Michelle Perner 2 , Alicia Berard 2 , Ann M. Carias 3 , Kenzie Birse 2 , John Schellenberg 2 , Melissa Lemke 4 , Annelie Tjernlund 5 , Garrett Westmacott 1 , Douglas Lauffenburger 6 , Kristina Broliden 5 , Lyle McKinnon 2 , Kelly Arnold 4 , Thomas Hope 3 , Adam Burgener 2 1 Public Health Agency of Canada, Winnipeg, MB, Canada, 2 University of Manitoba, Winnipeg, MB, Canada, 3 Northwestern University, Chicago, IL, USA, 4 University of Michigan, Ann Arbor, MI, USA, 5 Karolinska University Hospital, Stockholm, Sweden, 6 MIT, Cambridge, MA, USA

Poster Abstracts

94

CROI 2018