CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

After IVR removal, an increased probability of transition into CST IV (OR=7.75, CI=1.56-38.49), p<0.001) was observed, with a decrease in lactic acid levels (p<0.001). Negative binomial modeling of the most abundant taxa between week 3 (during IVR use) and 4 (1 week after IVR removal) showed significant increases in Gardnerella vaginalis, unclassified Prevotella sp., and P. timonensis, and decreases in L. crispatus. Conclusion: The shift in vaginal microbial communities from Lactobacillus- dominant types (CST I-III) to CST IV following removal of the ENG/EE IVR is concerning. Some women had a favorable response to the IVR, which may suggest this IVR is a therapeutic option for women with bacterial vaginosis. Further investigation is needed to fully assess interactions and safety of vaginal hormonal contraception in women with HIV-1. 1060 CONTRACEPTIVE USE INDUCES DURABLE SHIFTS IN THE FEMALE GENITAL-TRACT MICROBIOTA Bryan P. Brown 1 , Maricianah Onono 2 , Gonasangrie Nair 3 , Thesla Palanee- Phillips 4 , Caitlin W. Scoville 5 , Rubina Bunjun 6 , Tanko F. Ramla 6 , Kate Heller 5 , Jared Baeten 5 , Steven E. Bosinger 7 , Adam Burgener 8 , Jo-Ann Passmore 6 , Renee Heffron 5 , Heather Jaspan 1 1 Seattle Children's Research Institute, Seattle, WA, USA, 2 KEMRI-UCSF, Kisumu, Kenya, 3 Desmond Tutu HIV Foundation, Cape Town, South Africa, 4 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 5 University of Washington, Seattle, WA, USA, 6 University of Cape Town, Cape Town, South Africa, 7 Emory University, Atlanta, GA, USA, 8 University of Manitoba, Winnipeg, MB, Canada Background: Vaginal bacterial microbiota modulate genital immunity and susceptibility to HIV and other sexually transmitted pathogens. However, it is unclear how contraceptive use affects the composition and dynamics of these communities. Methods: Within the ECHO trial, designed to compare the relative HIV-1 incidence among women randomized to copper intrauterine device (Cu-IUD), levonorgesterol implant (LNG-implant), or DMPA-IM, this nested three-site (Cape Town, Johannesburg, Kisumu) sub-study aimed to evaluate the impact of these contraceptives on genital tract microbiota. 201 were randomly selected from among the 430 in the sub-study for analyses of samples collected at enrollment (pre-contraceptive initiation), 1-month, and 6-months post- contraceptive initiation. For all samples, the 16S rRNA gene was amplified and sequenced from fluid collected via lateral vaginal wall swabs. Results: Baseline Shannon diversity was elevated in women randomized to LNG-implant compared to DMPA-IM, but not Cu-IUD. After 1 month of use, there were no differences in Shannon diversity between randomization arms. However, after 6 months of use, there were significant differences in Shannon diversity between all arms, with women randomized to DMPA-IM displaying the lowest bacterial diversity (mean 0.583), followed by LNG-implant (mean 1.06) and Cu-IUD (mean 1.64). Lactobacillus abundance was significantly reduced between baseline and 6-months post-contraceptive initiation for women randomized to Cu-IUD, which was concurrent with a significant increase in taxa associated with Bacterial Vaginosis. Conversely, women who were randomized to DMPA-IM exhibited significant reductions in the abundance of dysbiotic Prevotella taxa. Significant differences in beta-diversity between randomization arms suggested that community-wide alterations persisted at both 1-month (p=0.034), and 6-months post contraceptive initiation (p=0.004), with women assigned to Cu-IUD transitioning to more diverse bacterial communities. Conclusion: These are the first data comparing vaginal bacteria among women randomized to effective contraceptives. That Cu-IUD elicits increases in overall bacterial diversity and abundance of dysbiotic taxa relative to DMPA-IM and LNG-Implant suggests that non-hormonal IUDs may have consequences on vaginal microbiota. These results are central to informing contraceptive options for sexual and reproductive health. 1061 GENITAL SECRETIONS FROMWOMEN WITH BACTERIAL VAGINOSIS ENHANCE HIV INFECTION EX VIVO Marla J. Keller 1 , Richard Hunte 1 , Rebecca Barnett 1 , Joyce Serebrenik 1 , Jessica McWalters 1 , April Dobkin 1 , Jessica Goymer 1 , Laurie Ray 1 , Lilia Espinoza 1 , Jessica M. Atrio 2 , Kerry Murphy 1 , Betsy Herold 1 1 Albert Einstein College of Medicine, Bronx, NY, USA, 2 Montefiore Medical Center, Bronx, NY, USA Background: Women with bacterial vaginosis (BV) are more susceptible to HIV. We hypothesize that increased HIV susceptibility is mediated by direct or

indirect effects of bacteria on mucosal immunity and the epithelial barrier. To test this hypothesis, we conducted a longitudinal study in women with clinical BV before and after treatment, quantified the ability of cervicovaginal fluid (CVF) to inhibit or enhance HIV infection ex vivo, and correlated the activity with vaginal microbiota, cytokines, chemokines and other soluble immune molecules. Methods: Cervicovaginal lavage and vaginal swabs were collected from 20 HIV negative adult women in Bronx, New York with symptomatic BV (3 or 4 Amsel criteria). Repeat sampling was done 1 week and 1 month after completion of 7 days of twice daily oral metronidazole treatment. Vaginal pH, Nugent scores, CVF cytokines and chemokines, CVF inhibitory or enhancing activity against HIV infection in a TZMbl assay with BaL, and quantities of select vaginal microbiota in swabs (qPCR) were measured. Results were compared between visits by Friedman’s test. Spearman correlation coefficients were calculated to assess associations between HIV inhibiting/enhancing activity and other measures. Results: Proinflammatory cytokines were significantly higher and chemokines were significantly lower in women with BV compared to sampling done after BV treatment (IL-1a p<0.001; IL-1b p=0.04; CXCL9 p=0.01; CXCL10 p=0.03). CVF fromwomen at the time of BV diagnosis enhanced HIV infection significantly by 26% (IQR -1%, 128%) and enhancement decreased significantly 1 month after treatment (p<0.05). HIV enhancement correlated positively with Nugent score (r=0.48), IL-1a (r=0.5), Gardnerella vaginalis (r=0.55), Atopobium vaginae (r=0.48), BVAB2 (r=0.4), Sneathia (r=0.62), and Megasphaera Type 2 (r=0.5) and negatively with L. crispatus (r=-0.4), MIP-1b (r=-0.43), CXCL9 (r=-0.4), and CXCL10 (r=-0.43) (all p<0.002). Preliminary mechanistic studies indicate that CVF increases the binding of HIV to target cells. Conclusion: CVF fromwomen with BV enhanced HIV in vitro and the enhancing activity was associated with specific BV-associated bacteria and IL-1a. Treatment with metronidazole led to a reduction in the enhancing activity. Additional mechanistic studies are in progress to better understand links between HIV enhancing activity and the vaginal microbiome. 1062 DMPA-IM DRIVES CERVICAL Th17 HIV TARGET-CELL ACCUMULATION IN WOMEN IN ECHO TRIAL Rubina Bunjun 1 , Tanko F. Ramla 1 , Shameem Jaumdally 1 , Hoyam Gamieldien 1 , Rushil Harryparsad 1 , Smritee Dabee 1 , Gonasangrie Nair 2 , Thesla Palanee- Phillips 3 , Maricianah A. Onono 4 , Caitlin W. Scoville 5 , Kate Heller 5 , Jared Baeten 5 , Heather Jaspan 6 , Renee Heffron 5 , Jo-Ann Passmore 1 1 University of Cape Town, Cape Town, South Africa, 2 Desmond Tutu HIV Foundation, Cape Town, South Africa, 3 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 4 KEMRI–Centre for Global Health Research, Kisumu, Kenya, 5 University of Washington, Seattle, WA, USA, 6 Seattle Children's Research Institute, Seattle, WA, USA Background: To definitively assess the relationship between selected contraceptive methods and HIV acquisition risk, the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial randomised women to the copper-T IUD, DMPA-IM and levonorgestrel (LNG) implant with HIV seroconversion as the primary endpoint. Within this trial, we nested mucosal CD4+ T cell studies to determine the impact of contraceptive initiation on Th17 HIV target cells in the genital tract as a potential mechanism for HIV risk. Methods: Cervical cytobrushes and cervicovaginal secretions fromwomen enrolled in the ECHO trial (n=80) were collected at baseline and within 3 months of initiating contraception. Cervical cytobrush-derived T cells were phenotyped ex vivo by multiparameter flow cytometry, staining for T cell (CD3, CD4, CD8), activation (CD38), mucosal homing (CCR5, a4b7), and Th17 subset markers (CCR6, CCR10). Soluble cytokines and chemokines were measured in secretions using 27-plex Luminex assay. Results: DMPA-IM induced an increase in the frequency of activated (CD38+) cervical Th17-like cells (p=0.04), while the other contraceptive arms did not. Despite no contraceptive specific changes in the overall expression of HIV receptors CCR5 or a4b7, 90% of all activated Th17 cells expressed either receptor and were therefore potentially infectable by HIV. Co-expression analyses revealed that women using DMPA-IM had a higher frequency of highly susceptible CD38+CCR5+a4b7+ Th17 cells compared to baseline. Neither the copper IUD nor LNG-implant induced an increase in any Th17 population expressing CD38, CCR5 or a4b7 in any combination. Increases in the frequency of susceptible Th17 populations in women using DMPA-IMwere not associated with higher concentrations of T cell chemotactic markers IL-8, Eotaxin, IP10, RANTES, MIP-1a

Poster Abstracts

CROI 2020 399