CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

WITHDRAWN

596

Poster Abstracts

597 Understanding the Relative Contributions of IDU and HCV on Systemic Immune Activation

Martin Markowitz 1 ; Sherry Deren 2 ; Charles Cleland 2 ; Melissa LaMar; Evelyn Silva 3 ; Pedro Batista 2 ; Leslie St. Bernard 1 ; Natanya Gettie 1 ; Haekyung Lee 4 ; Saurabh Mehandru 4 1 Aaron Diamond AIDS Rsr Cntr, New York, NY, USA; 2 Cntr for Drug Use and HIV Rsr, New York Univ Coll of Nursing, New York, NY, USA; 3 BOOM!Hlth, Bronx, NY, USA; 4 Icahn Sch of Med at Mount Sinai, New York, NY, USA Background: Persistent immune activation is associated with a variety of adverse clinical outcomes. People who inject drugs (PWID) have high levels of immune activation in blood and mucosal tissues; however, the relative contributions of chronic HCV infection, highly prevalent among PWIDs, and the non-sterile injection of illicit drugs have remained obscure. Methods: We recruited (N=48 for each group): 1) active injectors of heroin 2) individuals who ceased injecting heroin for 1-2 months 3) individuals who ceased injecting heroin for 3-4 months 4) healthy non-injecting volunteers. Soluble (including sCD14, hs-CRP, TNF-a, IFN-g, IL-10, MIP-1a) and cell associated (CD38+HLA-DR+ CD4 and CD8+ T cells) markers of immune activation were quantified. Mixed-effects regression models with random intercepts to account for participation in more than one group were used to compare groups on markers of immune activation. Results: Participant characteristics are shown in Table 1 below. Levels of IL-12p70, IL-15, IL-1b, IL-2, IL-4, and IL-6 determined by multiplex ELISA were at or below the level of detection in 50% or more of the active injectors and were not analyzed. Mean levels of selected markers of systemic and cellular immune activation are shown in Table 2 below. Participants in Groups 2 and 3 had statistically significantly lower levels of TNF-a and % CD4+ and CD8+ CD38+/HLA-DR+ T cells compared to actively injecting Group 1 subjects only if HCV infection was spontaneously controlled or if subjects were HCV uninfected (HCV-aviremic). sCD14 levels in HCV-aviremic Group 3 subjects were significantly lower than in aviremic Group 1 subjects and comparable to Group 4. Additionally, hs-CRP levels were significantly lower in Group 2 but not in Group 3 compared to Group 1 subjects. In contrast, in HCV-viremic subjects, the above parameters were not significantly different between the groups and were significantly higher than in the healthy non-injecting volunteers. Levels of IFN-g, IL-10, and MIP-1a were comparable across Groups 1, 2, and 3 independent of the presence/absence of viremia. Conclusions: Active IDU and HCV viremia are associated with persistent immune activation. Select markers of immune activation are significantly lower among the HCV-aviremic who cease injecting but not in those who are HCV viremic. These findings may have public health consequences. Aggressive treatment of HCV infection as well as enhanced harm reduction efforts should converge to optimize long-term outcomes.

239

CROI 2016