CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

1050 Persistently Elevated Macrophage Activation in HIV+Women Reporting Heavy Alcohol Use Seema N. Desai 1 ; Kathleen M.Weber 2 ; Jane Burke-Miller 3 ; Audrey L. French 2 ; Monica Gandhi 4 ; Mark H. Kuniholm 5 ; ElizabethT. Golub 6 ; Kendall Bryant 7 ; Alan Landay 1 ; Mardge Cohen 8 1 Rush University Medical Center, Chicago, IL, US; 2 CORE Center/Stroger Hospital of Cook County, Chicago, IL, US; 3 Hektoen Institute of Medicine, Chicago, IL, US; 4 University of California San Francisco, San Francisco, CA, US; 5 Albert Einstein College of Medicine, Bronx, NY, US; 6 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 7 National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, US; 8 Stroger Hospital of Cook County, Chicago, IL, US Background: Alcohol consumption is common in HIV infected women. Heavy alcohol consumption has been associated with accelerated HIV disease progression and poor health outcomes, mainly attributed to inadequate antiretroviral adherence. We hypothesized heavy alcohol consumption alters macrophage activation and inflammation and independently influences HIV disease progression. Methods: Women’s Interagency HIV Study (WIHS) participants who were hepatitis C seronegative were stratified into 4 groups: HIV+ and HIV- with the heaviest chronic alcohol consumption and abstainers, 50/group. Participants were matched on age, race, and education. Soluble macrophage activation marker (sCD163) and sTNF-RII, a marker of inflammation/activation, were measured using ELISA in a subset of n=25/group at 4 time points over 10 years (2001-11). ANOVA was used to examine differences between groups in soluble markers and multivariable random effects logistic and random linear regression models examined associations. Results: Across the study period, drinkers reported a mean of 21 drinks/week. Adjusting for HAART use, duration and self-reported adherence, HIV+ heavy drinkers (> 7 drinks/ week) were more likely to have a CD4 count<350 cells/mm 3 (OR=3.67, p=.005) and detectable viral load (OR=1.65, p=.051) than non-drinkers. sCD163 (mean ng/mL + sd) at baseline was highest in HIV+ drinkers 2098 (1582) compared to HIV+ abstainers 1355 (743), HIV- drinkers 1216 (551), and HIV- abstainers 1349 (673) (F=10.61, p<.001). sTNFRII expression at baseline (mean pg/mL + sd) was higher in both HIV+ drinkers 2692 (889) and HIV+ abstainers 2659 (1093) compared to HIV- drinkers 1697 (557) and HIV- abstainers 1893 (451) (F=4.21, p=.008). Both sCD163 & TNFRII did not significantly change over time. In multivariable longitudinal models, HIV+ drinkers had significantly higher sCD163 than other groups (p<.001); both HIV+ drinkers and HIV+ abstainers had significantly higher sTNFRII than HIV- women (p<.001 and p=.006 respectively). Among HIV+ women, both sCD163 & sTNFRII were significantly associated with elevated viral load (sCD163, p<.001; sTNFRII, p=.021) over time; sTNFRII was associated with lower CD4 cell counts (p=.001). Conclusions: Chronic heavy drinking is independently associated with HIV outcomes (CD4+ count and viral load). Persistently elevated level of sCD163 in HIV+ve heavy drinkers suggests a mediating role of macrophage activation with implications to persistent inflammation in HIV-infected women reporting heavy alcohol consumption. 1051 Is Survival Following HIV Seroconversion Still Improving, 17 Years After the Introduction of cART? Ashley Olson 1 ; Caroline Sabin 1 ; Maria Prins 2 ; Laurence Meyer 3 ; Julia del Amo 4 ; Genevieve Chene 5 ; Osamah Hamouda 6 ; GiotaTouloumi 7 ; Kholoud Porter 1 On behalf of the CASCADE Collaboration in EuroCoord 1 University College London, London, United Kingdom; 2 Public Health Service of Amsterdam, Amsterdam, Netherlands; 3 Inserm, Paris, France; 4 Instituto de Salud Carlos III, Madrid, Spain; 5 Inserm, Bordeaux, France; 6 Robert Koch Institute, Berlin, Germany; 7 University of Athens, Athens, Greece Background: Survival of HIV positive individuals has increased since the introduction of cART. We aim to determine if survival and disease free progression in Europe, Australia and Canada are still increasing up to 2013 and to provide updated survival estimates. Methods: Using CASCADE seroconverter data, we used Cox models to estimate the effect of calendar year on time from HIV seroconversion to death and disease free progression, adjusting for sex, mode of HIV transmission, age at seroconversion (SC), acute infection, and cohort. We investigated if there was interaction between sex, mode of HIV transmission and calendar year. Results: Of 30344 seroconverters with 234250 person years of follow up, 3190 died and 4126 developed AIDS. 25241 (82%) were male, 19024 (62%) infected through sex between men (MSM), 6725 (22%) sex between men and women (MSW), 3610 (12%) injection drug use (IDU) and 1496 (5%) other or unknown. The hazard ratio (HR) (95% CI) for death, compared to the pre-1997 hazard, decreased over time, falling to 0.44 (0.37, 0.53) in 1997 and reaching 0.08 (0.06, 0.12) in 2013. Similar trends were observed for disease progression with the HR falling to 0.56 (0.49, 0.64) in 1997 and to 0.10 (0.07, 0.14) in 2013. These trends were in parallel with increases in proportion of person time on cART from 17% in 1997 to 72% in 2013. A decreased risk of death was associated with female sex (compared to male sex (HR = 0.79 (0.71, 0.87)), and an increased risk with older age (HR = 1.53 (1.47, 1.59) per 10 year increase) and IDU (2.34, 2.13, 2.57)). We found a significant interaction between sex and mode of HIV transmission with calendar year (p<0.001). Among MSMMSW and other risk groups, HRs of AIDS/death were similar to that of the main analysis for both sexes. However among IDUs HRs of AIDS/death were 0.71 (0.54, 0.94) and 0.73 (0.50, 1.05) in 1997 and 0.29 (0.12, 0.67) and 0.48 (0.19, 1.20) in 2013 for males and females, respectively.

Poster Abstracts

Hazard Ratio (95% CI) for time to death and AIDS/death by calendar year using the CASCADE dataset Conclusions: Mortality from HIV infection continued to decrease until 2008 and stabilized thereafter. AIDS/mortality continued to decrease over time, stabilizing between 2008- 2012 and improving again in 2013. Percent of person time on cART has continued to increase until 2011, stabilizing around 70%.

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CROI 2015