CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Methods: Here, we analyse a subset of the ATHENA cohort, including individuals with date of infection estimated to within one year and with extensive and intensive clinical follow up. Because CD4 counts are intrinsically noisy, we separate the analysis of individual CD4 dynamics over time into a model of long-term trends of smoothed CD4 counts, and an observation model that relates actual CD4 measurements to the underlying smoothed counts. We use a monotonic spline smoothing model, and based on smoothed counts derive the average time to CD4 thresholds CD4 ≤ 500, CD4 ≤ 350, CD4 ≤ 200 cells/mm 3 as well as the average time to death, and the proportion of individuals starting in each category after seroconversion. We examine individual-level co-factors which influence these rates. We perform the analysis in both newly infected individuals that have not received antiretroviral therapy (ART) and those who have interrupted therapy for at least six months. Results: Amongst untreated individuals, the time spent in each compartment was on average 3.09 (CD4>500 cells/mm 3 ), 2.49 (CD4 350-500), 4.95 (CD4 200-350) and 1.07 (CD4 ≤ 200) years. Only 77% of individuals had CD4 >500 cells/mm 3 at or shortly after seroconversion. Set-point viral load (SPVL) was an important determinant of CD4 progression; individuals with ≥ 5 log10 copies/ml took 5.32 years to reach CD4 ≤ 200 cells/mm 3 compared to 11.53 years for SPVL <4 log10 copies/ml (see table). SPVL was not an important predictor of progression after treatment interruption, and CD4 dynamics were otherwise similar to pre-ART dynamics, providing evidence of true immune reconstitution during ART. Estimated average time (in years) to reaching CD4 200 cells/mm3, given current stage of infection, stratified by set point viral load (SPVL): mean estimate (95% confidence interval) Conclusions: Our analyses show that many individuals already have CD4 ≤ 500 cells/mm 3 at or shortly after seroconversion, and that set point viral load strongly influences initial CD4 cell count as well as rate of CD4 decline. Hence guidelines on treatment initiation should consider criteria based on both current CD4 count and viral load., while mathematical models should incorporate SPVL stratification. Our study also provides new estimates of CD4 dynamics after interruption of ART, which could be used in such models. 1049 IL-6 Partially Mediates the Effect of HIV Status on Survival Kaku So-Armah 1 ; Amy Justice 2 ; David Rimland 3 ; Maria Rodriguez-Barradas 4 ; Adeel A. Butt 5 ; David Leaf 6 ; RussellTracy 7 ; Mohammad Sajadi 8 ; Cynthia Gibert 9 ; Matthew S. Freiberg 10 1 Yale University School of Medicine, New Haven, CT, US; 2 VA Connecticut Healthcare System, West Haven, CT, US; 3 Veterans Affairs Medical Center, Atlanta, GA, US; 4 Veterans Affairs Medical Center, Houston, TX, US; 5 Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 6 Veterans Affairs Medical Center, Greater Los Angeles, CA, US; 7 University of Vermont, Burlington, VT, US; 8 Veterans Affairs Medical Center, Baltimore, MD, US; 9 Veterans Affairs Medical Center, Washington, DC, US; 10 Vanderbilt University School of Medicine, Nashville, TN, US Background: Biomarkers of inflammation (e.g. interleukin 6 (IL-6)) have been associated with mortality separately in HIV infected (HIV+) and uninfected cohorts. It is unclear whether inflammation as measured by IL-6 mediates and/or moderates the association between HIV status (infected and uninfected in same cohort) and mortality. Methods: Methods : Serum IL-6 was obtained from 1491 HIV+ and 820 uninfected participants from the Veterans Aging Cohort Study at baseline (2005-2007). Participants were followed until death or 7/25/2013. IL-6 values were compared using median regression. Cox models were used to assess mediation (Baron and Kenny) and moderation (interaction of HIV and IL-6). Results: Over a median of 6.9 (mean 6.4) years, 410 deaths occurred (15% of uninfected group, 19% of HIV+ group). HIV+ participants were younger, less likely to be female, had less prevalent cardiovascular disease, hypertension, diabetes, BMI>30 kg/m 2 , and more current hazardous alcohol consumption, and hepatitis C at baseline. Median [IQR] IL-6 level was higher among HIV+ versus uninfected people (2.1 [2.0] vs. 1.8 [2.1] pg/mL). Levels were particularly high among those with HIV-1 RNA between 500-10000 and ≥ 10000 copies/mL (2.0 [1.9] and 2.6 [2.8] pg/mL; p<0.05 for all comparisons to uninfected groups after confounder adjustment). Compared to uninfected people, HIV infected people with ongoing viral replication had increased mortality risk (Table 1). This association persisted after adjusting for confounders (Table 1). Further adjustment for IL-6 quartiles attenuated the association of HIV with mortality at higher HIV-1 RNA levels suggesting mediation is present (Table 1). There was a strong, stepwise increasing association of IL-6 quartiles with mortality (Table 1). This association was independent of HIV status. No statistically significant interactions were observed between HIV (stratified by HIV-1 RNA) and IL-6 quartiles in Cox models (p>0.05 for global tests of interactions).

Poster Abstracts

Conclusions: HIV infection with ongoing viral replication and elevated IL-6 were significantly and independently associated with mortality. To the degree that IL-6 captures effects of inflammation, our results support the conclusion that inflammation is an underlying mechanism for excess risk of mortality among HIV-infected people with ongoing viral replication compared to uninfected people.

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CROI 2015