CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: E replacement reduces %CCR5+CD4+ T cells in healthy postMP, suggesting it could decrease HIV acquisition in this group. Lack of a sizeable increase in %CCR5+ in healthy preMP after medically induced menopause may be due to short duration of ovarian hormone suppression, unknown effects of Lupron, or different age-related effects of E on CCR5 expression. 860 Progesterone Increases Are AssociatedWith HIV Susceptibility Factors inWomen AlisonY. Swaims 1 ;Tammy Evans-Strickfaden 1 ; L Davis Lupo 1 ; Alfredo Aguirre 2 ; Anandi Sheth 2 ; Igho Ofotokun 2 ; Clyde E. Hart 1 ; Richard E. Haaland 1 1 US Centers for Disease Control and Prevention (CDC), Atlanta, GA, US; 2 Emory University School of Medicine, Atlanta, GA, US Background: Native progesterone and progestin-based hormonal contraception are suspected of increasing women’s risk for acquiring sexually transmitted HIV. How progesterone and progestin-based contraceptives affect HIV target cells in women is uncertain. We investigated whether a population of HIV target cells in women, CD4 T lymphocytes, changes cell surface expression of the HIV CCR5 coreceptor, cell activation markers and response stimulation throughout a normal menstrual cycle. Methods: Peripheral blood mononuclear cells (PBMCs) isolated from 7 women at 5 time points throughout their normal menstrual cycles were tested for expression of the HIV coreceptor CCR5 and the activation marker CD38 using flow cytometry. PBMCs were also stimulated ex vivo in the presence of Golgi transport inhibitors and intracellular production of IL-2, IFN-g and TNF-a was detected using flow cytometry. Plasma estradiol and progesterone were measured at each time point using a luminex multiplex assay. A sustained rise in plasma progesterone levels marked the beginning of the luteal phase of the menstrual cycle. Results: The proportion of CCR5 and CD38 expressing CD4 memory T cells increased from 4% to 7% (p=0.03) from the follicular to luteal phase in 6 of 7 women. The proportion of ex vivo stimulated CD4 T cells with detectable intracellular TNF-a increased from 31% to 52% (p=0.006) from the follicular to the luteal phase while production of intracellular IL-2 and IFN-g remained unchanged. Increased populations of TNF-a producing cells were associated with higher plasma progesterone levels (p=0.04). The increase in TNF-a production occurred almost exclusively in cells which were also expressing IL-2 or both IL-2 and IFN-g. Time points with detectable increases in TNF-a production were the same or immediately preceding those where CCR5 and CD38 expression increased in 6 of 7 women. Estradiol levels were not associated with changes in CCR5, CD38, or ex vivo cytokine production. Conclusions: Our results suggest that increases in endogenous progesterone during the luteal phase of the menstrual cycle are associated with HIV target cells that have increased expression of the HIV coreceptor CCR5, higher activation levels, and an increased response to stimulation. Knowing if these progesterone effects exist in the genital mucosa of women could be an important measure for identifying risk factors of progestin-based hormonal contraceptives. 861 Changes in Vaginal Microbiota and Cytokines in HIV-1-SeronegativeWomen Initiating DMPA Alison C. Roxby 1 ; David N. Fredricks 2 ; Katherine Odem-Davis 1 ; Kristjana H. Ásbjörnsdóttir 1 ; Linnet Masese 1 ;Tina L. Fiedler 2 ;Walter Jaoko 3 ; James N. Kiarie 3 ; Julie M. Overbaugh 2 ; R Scott McClelland 1 1 University of Washington, Seattle, WA, US; 2 Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, US; 3 University of Nairobi, Nairobi, Kenya Background: Depot-medroxyprogesterone acetate (DMPA) has been associated with HIV acquisition in African women. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation, a mechanism through which DMPA may modify HIV susceptibility. Methods: In a prospective cohort study of high-risk Kenyan women, we collected monthly vaginal swabs over 1 year pre- and post-DMPA to evaluate microbiota and immune mediators. All women initiating DMPA were included. Using quantitative PCR with specific bacterial primers, we measured quantities of Lactobacillus crispatus, L. jensenii, L. iners , Gardnerella vaginalis , and total bacterial load (16S rRNA gene levels) on vaginal swabs. Six vaginal immune mediators were measured with ELISA. Trends in detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression models; cytokine trends associated with DMPA use were estimated using tobit random-effects regression. Results: From 2010-2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median 6 visits/woman (range 3-8)). The median time of DMPA-exposed follow-up was 8.4 months (range 1.5-11.6). Seven women (46%) had bacterial vaginosis (BV) within 70 days before DMPA start. L. iners was detected in 13 women (87%) prior to DMPA start, but other lactobacilli were rarely detected. G. vaginalis, present in all women pre-DMPA, declined by 0.21 log 10 copies/swab per month after DMPA exposure (p=0.011). Total vaginal bacterial load declined by 0.08 log 10 copies/swab per month of DMPA use (p=0.017). Sustained declines in quantities of interleukin (IL)-6 (p=0.025), IL-8 (p=0.041) and IL-1 receptor antagonist (p<0.001) were noted after starting DMPA. Nine women (60%) had L. crispatus detected after DMPA start; L. crispatus detection was significantly correlated with lower levels of IL-6 and IL-8 (p=0.009, p=0.02 respectively). No decrease in BV, vaginal pH or discharge was seen after DMPA start. Declines in G. vaginalis and immune mediators were preserved after adjustment for sexual behavior, condom use, BV, antibiotic use and vaginal washing. Conclusions: Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. We adjusted for likely behavioral and biological confounders, providing greater evidence that changes seen may be strongly related to DMPA. Further studies are warranted to outline specific components of the vaginal microbiota influenced by DMPA use, and the impact on HIV susceptibility.

Poster Abstracts

862 A Thinned Vaginal Stratum Corneum Is a Susceptibility Factor for SHIV Acquisition Ellen Kersh ; Jana Ritter; Katherine Butler; Sharon Dietz Ostergaard; Debra Hanson; Sherif Zaki; Janet McNicholl US Centers for Disease Control and Prevention, Atlanta, GA, US

Background: Biological mechanisms for increased HIV acquisition risk due to hormonal influences in women remain insufficiently understood. Vaginal epithelial thinning occurs during periods of high progesterone such as hormonal contraception or the luteal menstrual phase. It is unclear whether and to what extent this facilitates HIV entry. The study objective was to quantitatively evaluate vaginal epithelial thinning during the menstrual cycle and to determine any correlative relationship with susceptibility to SHIV infection.

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CROI 2015