CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Results: Of 5601 patients, 56 %were women, median age was 34 years and 35% had a CD4 baseline between 351-500 cells. During 3737 person-years follow up, there were 128 deaths. Mortality rates were 79.7 deaths per 1000 person-years (95% CI 64.4- 98.7) in the CD4 0-200 category, 22 deaths per 1000 person-years (95% CI 15.2-31.9) in the CD4 201-350 and 11.3 (95% CI 6.9-18.5) in the CD4 351-500. Differences in mortality between the last two groups were statistically significant (log rank test: p=0.03) Retention after 12 months on ART was 78.7%, 86.7% and 86.9% respectively for the CD4 0-200, 201-350 and 351-500 categories Conclusions: Our analysis found decreased mortality in the first year of ART in patients started with a baseline CD4 above 350 cells compared with those initiated with CD4 201-350 cells suggesting that the newWHO recommendations can also have individual clinical benefit in resource limited settings. Retention at 12 months in both groups was similar and above 85%. 578 Effect of ART on Mortality Generalized to Newly HIV-Diagnosed Persons in the USA Catherine R. Lesko 1 ; Stephen R. Cole 1 ; H. Irene Hall 3 ; Michael J. Mugavero 2 1 University of North Carolina, Chapel Hill, NC, US; 2 University of Alabama at Birmingham, Birmingham, AL, US; 3 US Centers for Disease Control and Prevention (CDC), Atlanta, GA, US Background: Existing estimates of the effect of ART on survival have come from interval and clinical cohorts that differ on patient demographic and clinical characteristics from recently HIV-diagnosed persons in the United States (US) (the target population). If the effect of ART varies with respect to these same patient characteristics, then the magnitude of existing estimates of the effect of ART on survival may not be directly generalizable to the recently diagnosed US population. Methods: Patients (n=12,547) initiating HIV care in eight academic medical centers in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) after January 1, 1998 were followed until death from any cause, administrative censoring at 5 years after therapy initiation or the end of follow up on December 31, 2011. The target population was persons diagnosed with HIV in the US between 2009 and 2011, which was provided by the Centers for Disease Control and Prevention from national HIV surveillance data. We estimated 5-year mortality from the complement of standardized Kaplan-Meier survival functions and described the relative reduction in the hazard of mortality due to ART using a marginal structural Cox proportional hazards model. Bias due to confounding and drop out were controlled using inverse probability weights for treatment and drop out. The effect of ART was estimated within subgroups defined by a priori selected patient demographic and clinical characteristics using stratified analyses. We standardized our final estimate of the effect of ART on survival to the recently HIV-diagnosed population using inverse probability weights for generalizability. Results: The hazard of all-cause mortality among ART initiators was 0.33 (95% CI: 0.25, 0.43) times the hazard among non-initiators. The protective effect of ART was stronger among patients with no history of injection drug use, lower CD4 cell count at baseline, no prior AIDS diagnosis, and non-Hispanic white race/ethnicity. Although conditions were present that might preclude generalizability of the study estimate, the HR among persons recently HIV-diagnosed in the US was similar (HR=0.32, 95% CI: 0.23, 0.45). Conclusions: We demonstrate the use of formal methods for generalizing an estimate of effect from one cohort to a different target population. The similarity of the results in both the CNICS cohort and the recently HIV-diagnosed provides reassuring evidence for the external validity of research conducted in the CNICS. 579 Association of CD4:CD8With Cause-Specific Mortality in Patients on Long-Term ART Margaret T. May 1 ; AdamTrickey 1 ; Dominique Costagliola 6 ; Peter Reiss 4 ; Santiago Moreno 5 ; John Gill 3 ; Colette Smith 2 ; Suzanne M. Ingle 1 ; Jonathan A. Sterne 1 On behalf of the AntiretroviralTherapy Cohort Collaboration (ART-CC) 1 University of Bristol, Bristol, United Kingdom; 2 University College London, London, United Kingdom; 3 University of Calgary, Calgary, Canada; 4 Academic Medical Center University of Amsterdam, Amsterdam, Netherlands; 5 Hospital Ramón y Cajal, Madrid, Spain; 6 UMR S 1136, Inserm et Sorbonne Universités, Université Pierre et Marie Curie, Paris, France Background: Patients with advanced HIV disease have low CD4:CD8 ratios. These improve with effective ART, but increases in ratios are largely due to higher CD4 counts with persistently high CD8 counts limiting further normalization of the ratio, even after 5 years of ART. Low CD4:CD8 ratios are associated with mortality in elderly HIV-negative people, and have been suggested to reflect HIV-related immune senescence. Methods: Adult patients from 12 European and North American cohorts contributing to the Antiretroviral Therapy Cohort Collaboration were followed for cause-specific mortality from 5 years after starting ART. Baseline CD4 and CD8 counts were those nearest to and within 3 months of 5 years after ART start. We used Cox models, stratified by cohort, to estimate hazard ratios (HR) for subsequent all-cause, AIDS-related, and non-AIDS related (excluding unnatural deaths) mortality comparing patients with CD4:CD8 ratio ≥ 0.5 and < 0.5 (reference group), stratified by CD4 count (< 350, ≥ 350, and ≥ 500 cells/mm 3 ). We fitted models that were unadjusted; adjusted for CD4; and additionally adjusted for sex, age, IDU transmission group, ART start year, AIDS and viral suppression at 5 years. Results: During 98,438 person-years 902/20,464 patients died. Cause of death was available in 63% of deaths. Median (inter-quartile range) CD4:CD8 ratio 5 years after ART start was 0.61 (0.40, 0.89) and 0.41 (0.23, 0.72) in those who survived and died, respectively (0.23 (0.09, 0.41) for AIDS deaths; 0.45 (0.27, 0.77) for non-AIDS deaths). At 5 years, 9698 (47%) patients had CD4:CD8 ratio >1. Lower CD4:CD8 ratios were associated with mortality in all groups, but these associations were completely attenuated after adjustment for CD4 in those with CD4 counts <350 cells/mm 3 . By contrast, the adjusted HR (95% CI) in patients with CD4 ≥ 350 cells/mm 3 was 0.68 (0.56, 0.84). In patients with CD4 ≥ 500 cells/ mm 3 the adjusted mortality HR (95% CI) for CD4:CD8 ≥ 0.5 (v. < 0.5) was 0.71 (0.32, 1.56). In patients with CD4 ≥ 350 cells/mm 3 low CD4:CD8 was associated with both non-AIDS and AIDS-related deaths, but confidence intervals were wide.

Poster Abstracts

Conclusions: CD4:CD8 ratios may be useful for monitoring mortality risk in patients on long-term ART.

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CROI 2015