CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

623 ASSOCIATION OF INFLAMMATION AND COAGULATION WITH CLINICAL RISK IN THE START TRIAL Jason Baker , Shweta Sharma, Birgit Grund, for the INSIGHT START (StrategicTiming of AntiRetroviralTreatment) Study Group Univ of Minnesota, Minneapolis, MN, USA

Background: The START trial demonstrated that immediate (at CD4 >500cells/µL) versus deferred (to CD4 <350 cells/µL) antiretroviral therapy (ART) reduced a composite outcome of AIDS, serious non-AIDS (SNA) events and death (N Eng J Med 2015). The SMART trial demonstrated that inflammation and coagulation biomarkers strongly predict risk for these events. We characterized associations for clinical event risk in START with inflammation, coagulation and vascular injury biomarkers. Methods: Biomarkers (Table) were measured from stored plasma at baseline; levels analyzed on the log2 scale. Associations of biomarker levels with event risk were estimated with Cox regression, pooled across treatment groups. Homogeneity of the associations across treatment groups, age and gender was assessed. Models were adjusted for age, gender, and treatment group and stratified by region. Results: Of the 4685 participants enrolled in START, baseline biomarker levels were available for 4299 (92%). Mean follow-up was 3.0 years. There were 129 primary events (AIDS, SNA or death); 57 AIDS or AIDS-death events (23 tuberculosis [TB]), 74 SNA or non-AIDS deaths, 50 cancer (AIDS or non-AIDS; 12 Kaposi sarcoma), and 24 CVD. Higher levels of IL-6 and D-dimer were associated with higher risk of AIDS and SNA events (HRs ranged 1.4-1.5 per doubling of biomarker) (Table); associations with AIDS were driven by TB (HRs 1.7-1.8, p<0.008). Higher IL-6 levels are associated with CVD. No biomarkers were associated with cancer risk. Associations of biomarkers with clinical event risk did not differ across immediate and deferred groups, except for sVCAM with AIDS or TB and sICAM with TB (positive associations only seen in deferred arm), and sICAM for SNA (non-significant association in both groups). Significant biomarker associations were consistent across age and gender, except for D-dimer with AIDS (stronger at lower age), and sICAM with TB (stronger at higher age). Conclusion: Among a diverse global population of HIV+ persons with high CD4 counts, higher IL-6 and D-dimer levels had the strongest association with risk for SNA, AIDS, and their composite. These data, combined with prior biomarker work from INSIGHT trials, demonstrate that IL-6 and D-dimer consistently predict clinical risk across a broad spectrum of CD4 counts for those both ART naïve or treated. Randomized clinical trials are needed to evaluate whether lowering these biomarker levels decreases clinical risk.

Poster and Themed Discussion Abstracts

624 HIV VIRAL BURDEN ASSOCIATED WITH SUBCLINICAL CORONARY ARTERY DISEASE IN HIV+ MEN Sabina Haberlen 1 , Ruibin Wang 1 , Frank J. Palella 2 , Lisa Jacobson 1 , Todd Brown 1 , Mallory Witt 3 , Kathryn Berlacher 4 , Matthew Budoff 5 , Alison Abraham 1 , Wendy Post 1

CROI 2017 266