CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

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. 1086 Mobile VMMC Teams in Tanzania See Older Clients and Have Higher Followup Rates Augustino M. Hellar 1 ; Dorica Boyee 1 ; Hally Mahler 1 ; Marya Plotkin 1 ;Touma Ng’wanakilala 1 ; Kelly Curran 2 ;Tigistu Ashengo 2 ; Hawa Mziray 1 ; Erick Mlanga 3 ; Sifuni Koshuma 4 1 Jhpiego, Dar es Salaam, United Republic of Tanzania; 2 Jhpiego, Baltimore, MD, US; 3 US Agency for International Development, Dar es Salaam, United Republic of Tanzania; 4 Ministry of Health and Social Welfare, Iringa, United Republic of Tanzania Background: Tanzania has rolled out Voluntary Medical Male Circumcision (VMMC) since 2009 in 12 priority regions with high HIV and lowmale circumcision rates. More than 390,000 clients have been served in Iringa, Njombe and Tabora regions with support from Jhpiego and USAID. Nearly 80% of clients reached are aged 10-19 years. Iringa and Njombe are approaching their original 80% coverage target. Service delivery modalities include routine, in which services are delivered in larger health facilities, typically at low volume, and campaigns where teams of providers move into new communities and do 1-3 week bursts of intense, high-volume provision of services. In May 2014, mobile services were introduced specifically to serve the hard-to-reach clients not reached by other modalities. This roving team of providers, move along villages to provide VMMC services even in non-facility settings. The analysis presents findings on differences in the three modalities. Methods: Secondary data review was conducted on 148,880 individual records, stripped-of identifiers from all three regions from October 2013-August 2014, the year when mobile teams were introduced. Records were broken into three modalities: campaign, routine and mobile. Frequencies were compared between the modalities and Chi 2 was used to test for the significance of the differences. Results: 76% of the 148,880clients circumcised during the year were aged <20 years. Mobile teams reached older clients compared to other service delivery modalities (p<0.001), as shown below. Overall HIV testing uptake was high (97%) regardless of the modality. A higher proportion tested HIV positive in the routine followed by mobile modalities (2.1% and 1.4% respectively). Follow-up rates were significantly higher in the mobile modality both for 1 st and 2 nd visits (91.7% and 63.1% respectively) compared to static modality (70% and 36% respectively); p-value < 0.001).

Oral Abstracts

115

CROI 2015