HIV Infection, HCV Coinfection, and Alcohol Use: Associations with Microbial Translocation and Immune Activation

Abstract

Background: Human immunodeficiency virus (HIV) infection and heavy drinking independently promote microbial translocation and inflammation. However, it is not known how alcohol use may affect these processes in people living with HIV (PLWH). This study tested the hypothesis that alcohol exacerbates innate immune dysfunction in PLWH.Methods: Participants were 75 PLWH 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-year study period. Recent alcohol use was assessed with the Timeline Followback Interview. Biomarkers of microbial translocation (lipopolysaccharide, LPS) and immune activation (lipopolysaccharide binding protein, LBP; soluble CD14, sCD14; soluble CD163, sCD163) were quantified using enzyme-linked immunosorbent assays. Analyses tested 2 hypotheses: (i) that biomarker levels would be significantly higher in PLWH than controls with comparable alcohol use and (ii) that current alcohol use would exacerbate biomarker elevations in PLWH. The second analysis included the interaction of alcohol use with hepatitis C virus (HCV) coinfection.Results: Groups were matched on alcohol use, smoking, and other drug use. All biomarkers were significantly higher in PLWH relative to controls (LBP: p = 0.005; LPS: p = 0.014; sCD14: p < 0.001; sCD163: p < 0.001). In PLWH, alcohol use showed a significant, positive association with sCD163, but not with other biomarkers. However, the interaction of alcohol use with HCV coinfection was significant for all biomarkers (LBP: p = 0.002; LPS: p = 0.026; sCD14: p = 0.0004; sCD163: p = 0.001). In pairwise tests with sequential Bonferroni correction, HIV/HCV coinfected individuals who drank heavily had significantly higher sCD163 compared to coinfected nondrinkers and to HIV monoinfected nondrinkers, moderate drinkers, and heavy drinkers (ps < 0.005). Coinfected moderate drinkers had significantly higher sCD163 than each monoinfected group (ps < 0.003). In addition, sCD14 was significantly higher in coinfected moderate drinkers than coinfected nondrinkers (p = 0.027).Conclusions: As predicted, PLWH had higher levels of LBP, LPS, sCD14, and sCD163 than uninfected individuals with similar alcohol use. In PLWH, alcohol by itself was significantly associated only with higher sCD163. However, heavy or moderate alcohol use was associated with elevations in macrophage activation (sCD163) and monocyte activation (sCD14) in HIV/HCV coinfected individuals.

Identification of Aberrantly Methylated Differentially CpG Sites in Hepatocellular Carcinoma and Their Association With Patient Survival

“…Most studies concerned the acute-phase response of LBP to bacterial infection ( 46 – 48 ); few studies focused on the role of LBP in virus infection, and the underlying mechanisms of LBP remain unclear. Of note, a previous study showed that people infected with HIV had a significantly higher level of LBP than uninfected individuals ( 49 ). There was also a study indicating that patients with hepatitis C virus (HCV) infection had significantly elevated LBP compared to those without HCV infection ( 50 ).…”

“…LBP is the binding protein of lipopolysaccharide. Most studies concerned the acute-phase response of LBP to bacterial infection (46)(47)(48); few studies focused on the role of LBP in virus infection, and the underlying mechanisms of LBP remain unclear. Of note, a previous study showed that people infected with HIV had a significantly higher level of LBP than uninfected individuals (49).…”

Neuroimaging and Cognitive Evidence for Combined HIV‐Alcohol Effects on the Central Nervous System: A Review

“…Consistent with HCV’s adverse hepatic and inflammatory effects, HIV/HCV/AUD comorbidity further impacts brain and cognition. HIV/HCV/AUD comorbidity is associated with greater monocyte activation relative to singly‐ or doubly diagnosed groups, consistent with increased gut microbial translocation (Monnig et al, 2019).…”

“…Microbial translocation is linked to increased risk of HAD (Ancuta et al, 2008); however, as biomarkers of microbial translocation do not fully normalize after ART induction (Marchetti et al, 2013), even virally suppressed PLWH are at risk of inflammation-linked neurocognitive dysfunction (Imp et al, 2017). In recent years, this pathway has been identified as a contributor to neurological dysfunction and its neurocognitive sequelae in HIV/ AUD (Monnig et al, 2019;Royal et al, 2016). Biomarkers of microbial translocation and related immune activation predict reductions in processing speed in this population (Monnig et al, 2017).…”

Clinical and Personal Status in Women With Hiv/HCV Co-Infection, Alcohol and Drug Use at Stages of the Disease

“…Употребление ПАВ пациентами с коинфекцией ВИЧ/ВГС является важным фактором, приводящим к дополнительным печеночным и внепеченочным повреждениям, нарастанию токсических и воспалительных изменений, ухудшению показателей иммунного статуса, необходимости существенно корректировать характер медицинской помощи [2].…”