CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

859 Estrogen Replacement in Healthy Postmenopausal Women Reduces %CCR5+ CD4+ T Cells Amie Meditz 1 ; Samantha MaWhinney 2 ; Kerrie Moreau 2 ; Kelsey Melander 2 ; Joy Folkvord 2 ;Wendy Kohrt 2 ; MargaretWierman 2 ; Elizabeth Connick 2 1 Boulder Community Health, Boulder, CO, US; 2 University of Colorado Anschutz Medical Campus, Aurora, CO, US

Background: CCR5 is elevated on whole blood and cervical CD4+ T cells of healthy postmenopausal women (postMP) compared to premenopausal women (preMP), suggesting increased risk of HIV acquisition in older women. To test whether estrogen (E) downregulates CCR5, we evaluated CCR5 expression in healthy postMP who received E replacement and preMP who underwent medical induction of menopause. Methods: Healthy HIV- women were recruited to A) 2 studies of E patch (estradiol 0.05 or 0.075 mg/day) versus placebo (PL) in postMP; B) a study of preMP who underwent menopause induction via GnRH agonist Lupron (L) with add-back E patch (0.075 mg/day) or placebo (PL); and C) an observational study of preMP. Blood was collected from preMP (early follicular phase) and postMP at baseline. Repeat sampling occurred 2 days to 4 weeks following E or PL in postMP and 4 weeks following dosing of L+E or L+PL to preMP. %CCR5+ and %CCR5+HLA-DR+CD38+ (activated) CD3+CD4+ cells were determined by flow cytometry, and CCR5 Δ 32 genotype by molecular analyses. Data were analyzed using mixed models and nonparametric methods. Results: In postMP after E, %CCR5+ and %CCR5+activated cells tended to decrease (median Δ , -3.4%; p=0.16, and -5.8%; p=0.28, respectively; n=10). PostMP+PL exhibited small changes in these parameters (median Δ , -0.4%, p=0.10 and -0.8%; p=0.60, respectively; n=15). In preMP, there were statistically nonsignificant decreases after L+PL in %CCR5+ (median Δ , -0.88%, p=0.28; n=11) and %CCR5+activated cells (median Δ , -3.4%, p=0.57; n=9). PreMP who received L+E had median changes of -0.23% (p=0.82; n=9) and 7.4% (p=0.69; n=7), respectively. Across all subjects, after controlling for CCR5 Δ 32 genotype (p=0.29), there was a 4.2% increase in %CCR5+ (95% CI 1.5%, 6.9%; p=0.003) for every 10-year age increase (Figure). PostMP+E had 6.2% lower %CCR5+ than postMP (95% CI -10.9%, -1.6%; p=0.01). Estimated %CCR5+ tended to be lower in PreMP following L+PL (-2.7%, 95% CI -7.1%, 1.8%; p=0.23), inconsistent with the hypothesis that induction of menopause would substantially increase CCR5 expression. Similar trends were seen in %CCR5+activated cells.

Oral 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. 858 CCR5 Expression in HIV-UninfectedWomen Receiving Hormonal Contraception Athe Tsibris 1 ; Gaia Sciaranghella 2 ; CuiweiWang 3 ; Kerry Murphy 4 ; Zaher Mehri 5 ; Ruth M. Greenblatt 6 ; Mardge Cohen 7 ; Elizabeth Golub 8 ; HeatherWatts 9 ; Mary A.Young 3 1 Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, US; 2 Ragon Institute of MIT, MGH and Harvard, Boston, MA, US; 3 Georgetown University Medical Center, Washington, DC, US; 4 Albert Einstein College of Medicine, Bronx, NY, US; 5 University of Vermont College of Medicine, Burlington, VT, US; 6 University of California San Francisco, San Francisco, CA, US; 7 Stroger Hospital and Rush University and CORE Center, Chicago, IL, US; 8 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 9 The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, US Background: Hormonal contraception may influence a woman’s susceptibility to HIV-1 infection. HIV infectivity increases as host receptor and coreceptor expression levels increase. We investigated the effect of hormonal contraception on HIV-1 receptor and coreceptor peripheral blood mononuclear cell (PBMC) expression. Methods: We used participant samples collected from The Women’s Interagency HIV Study (WIHS) between 2004 to 2011 and determined the CD4, CCR5, and CXCR4 expression levels on PBMC from HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA, n=32), the levonorgestrel releasing intrauterine device (LNG-IUD, n=27), or oral contraceptive pills (OCP, n=32). Women who did not use hormonal contraception (n=33) served as a comparator group. Groups were matched by age and race and one sample per participant per group was analyzed. Our monoclonal antibody panels identified monocyte, monocytoid dendritic cell, plasmacytoid dendritic cell, CD8 + T cell, and CD4 + T cell subpopulations. Monocytoid and plasmacytoid dendritic cells were analyzed together as a combined dendritic cell (DC) group. We compared the proportions of cells expressing CD4 and HIV coreceptors. Results: LNG-IUD users had an increased proportion of CD4 + and CD8 + T cells that expressed CCR5 (4.8 ± 0.4% and 12.5 ± 1.2%, respectively), relative to women on OCP (3.1 ± 0.3% and 8.2 ± 0.7%, p<0.01 and p<0.05) or no hormonal contraception (3.4 ± 0.3% and 7.6 ± 0.6%, p<0.05 and p<0.01). LNG-IUD use was associated with a 35% relative increase in the proportion of helper T cells that expressed CCR5 over that observed with the use of OCP and a 29% increase when compared to the use of no hormonal contraception. Increased CCR5 expression was associated with changes on central (T CM ) and effector memory (T EM ) T cells (p<0.01 for all comparisons). Relative increases of 6-12% in the magnitude of cellular T CM and T EM CCR5 expression were observed in the DMPA and LNG-IUD groups, compared to the OCP and no hormonal contraception groups (p<0.01 for all comparisons). No differences in the proportion of monocytes or dendritic cells that expressed CCR5, or hormone-associated changes in PBMC CD4 or CXCR4 expression levels, were detected. Conclusions: The use of the LNG-IUD and, to a lesser extent, DMPA was associated with increased CCR5 expression on peripheral T cells. Comparative work in female reproductive tract tissues and blood is needed to further evaluate contraception-associated increases in CCR5 expression.

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CROI 2015