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However, it is not known how alcohol use may affect these processes in people living with HIV<\/jats:styled-content> (PLWH<\/jats:styled-content>). This study tested the hypothesis that alcohol exacerbates innate immune dysfunction in PLWH<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Participants were 75 PLWH<\/jats:styled-content> and 34 uninfected controls. Groups were recruited to have similar proportions of nondrinkers, moderate drinkers, and heavy drinkers. Substance use data and plasma samples were collected at up to 3 visits over a 5\u2010year study period. Recent alcohol use was assessed with the Timeline Followback Interview. Biomarkers of microbial translocation (lipopolysaccharide, LPS<\/jats:styled-content>) and immune activation (lipopolysaccharide binding protein, LBP<\/jats:styled-content>; soluble CD<\/jats:styled-content>14, sCD<\/jats:styled-content>14; soluble CD<\/jats:styled-content>163, sCD<\/jats:styled-content>163) were quantified using enzyme\u2010linked immunosorbent assays. Analyses tested 2 hypotheses: (i) that biomarker levels would be significantly higher in PLWH<\/jats:styled-content> than controls with comparable alcohol use and (ii) that current alcohol use would exacerbate biomarker elevations in PLWH<\/jats:styled-content>. The second analysis included the interaction of alcohol use with hepatitis C virus (HCV<\/jats:styled-content>) coinfection.<\/jats:p><\/jats:sec>Results<\/jats:title>Groups were matched on alcohol use, smoking, and other drug use. All biomarkers were significantly higher in PLWH<\/jats:styled-content> relative to controls (LBP<\/jats:styled-content>: p<\/jats:italic>\u00a0=\u00a00.005; LPS<\/jats:styled-content>: p<\/jats:italic>\u00a0=\u00a00.014; sCD<\/jats:styled-content>14: p<\/jats:italic>\u00a0<\u00a00.001; sCD<\/jats:styled-content>163: p<\/jats:italic>\u00a0<\u00a00.001). In PLWH<\/jats:styled-content>, alcohol use showed a significant, positive association with sCD<\/jats:styled-content>163, but not with other biomarkers. However, the interaction of alcohol use with HCV<\/jats:styled-content> coinfection was significant for all biomarkers (LBP<\/jats:styled-content>: p<\/jats:italic>\u00a0=\u00a00.002; LPS<\/jats:styled-content>: p<\/jats:italic>\u00a0=\u00a00.026; sCD<\/jats:styled-content>14: p<\/jats:italic>\u00a0=\u00a00.0004; sCD<\/jats:styled-content>163: p<\/jats:italic>\u00a0=\u00a00.001). In pairwise tests with sequential Bonferroni correction, HIV<\/jats:styled-content>\/HCV<\/jats:styled-content> coinfected individuals who drank heavily had significantly higher sCD<\/jats:styled-content>163 compared to coinfected nondrinkers and to HIV<\/jats:styled-content> monoinfected nondrinkers, moderate drinkers, and heavy drinkers (p<\/jats:italic>s\u00a0<\u00a00.005). Coinfected moderate drinkers had significantly higher sCD<\/jats:styled-content>163 than each monoinfected group (p<\/jats:italic>s\u00a0<\u00a00.003). In addition, sCD<\/jats:styled-content>14 was significantly higher in coinfected moderate drinkers than coinfected nondrinkers (p<\/jats:italic>\u00a0=\u00a00.027).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>As predicted, PLWH<\/jats:styled-content> had higher levels of LBP<\/jats:styled-content>, LPS<\/jats:styled-content>, sCD<\/jats:styled-content>14, and sCD<\/jats:styled-content>163 than uninfected individuals with similar alcohol use. In PLWH<\/jats:styled-content>, alcohol by itself was significantly associated only with higher sCD<\/jats:styled-content>163. However, heavy or moderate alcohol use was associated with elevations in macrophage activation (sCD<\/jats:styled-content>163) and monocyte activation (sCD<\/jats:styled-content>14) in HIV<\/jats:styled-content>\/HCV<\/jats:styled-content> coinfected individuals.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14032","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T17:11:42Z","timestamp":1553533902000},"page":"1126-1134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["HIV<\/scp> Infection, HCV<\/scp> Coinfection, and Alcohol Use: Associations with Microbial Translocation and Immune Activation"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3166-2336","authenticated-orcid":false,"given":"Mollie A.","family":"Monnig","sequence":"first","affiliation":[{"name":"Center for Alcohol and Addiction Studies Brown University Providence Rhode 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