Unhealthy Alcohol Use is Associated with Monocyte Activation Prior to Starting Antiretroviral Therapy

Abstract

Background Alcohol use may accelerate HIV disease progression, but the plausible biological mechanisms have not been clearly elucidated. Methods HIV-positive persons who were not on anti-retroviral therapy (ART) completed the baseline assessment for a longitudinal study examining the association of alcohol use with HIV disease markers. Oversampling drinkers, baseline samples were tested for markers of monocyte activation (sCD14), inflammation (IL-6), and coagulation (D-dimer). We defined “unhealthy alcohol use” as testing positive using the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C; ≥ 3 for women and ≥ 4 for men) in the past 3 months or testing positive using a biomarker of heavy drinking, phophatidylethanol (PEth; ≥ 50 ng/ml). Multiple linear regression was used to examine the associations of unhealthy alcohol use with sCD14, Log10 IL-6, and D-dimer. Results Compared to those who were abstinent from alcohol, unhealthy drinkers had significantly higher sCD14 levels (mean = 1,676 vs. 1,387 ng/ml; mean difference (95% CI) = 289 (83, 495), p < 0.01). In analyses adjusted for demographic factors, current cigarette smoking, and HIV disease markers, unhealthy drinkers continued to display significantly higher sCD14 levels compared to those who were abstinent from alcohol (adjusted mean = 1,670 vs. 1,406 ng/ml; adjusted mean difference (95% CI) = 264 (47, 480), p = 0.02). Unhealthy alcohol use was not significantly associated with IL-6 or D-dimer levels. Conclusions unhealthy alcohol use was independently associated with a marker of monocyte activation (i.e., higher sCD14) that predicts mortality in treated HIV infection. Longitudinal research should examine if unhealthy alcohol use predicts changes in sCD14 prior to and following ART initiation.

Alcohol and dietary factors associate with gut integrity and inflammation in HIV‐infected adults

“… This can occur by inducing nitric oxide synthase and Nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signalling, which can result in differential expression of tight junction proteins, impairment of gut integrity indirectly through inflammation, or an increase in the LPS‐producing gram‐negative bacterial microflora. Heavy alcohol use in HIV‐infected patients has been found to accelerate HIV disease progression, and one study found an association between unhealthy alcohol intake and higher sCD14 in untreated HIV‐infected subjects in Uganda; however, to the best of our knowledge, no one has previously demonstrated associations of alcohol use with such a broad range of markers of microbial translocation, immune activation, and inflammation in treated HIV‐infected adults. This evidence is consistent with the hypothesis that alcohol, in particular liquor, use increases translocation of LPS, which interacts with LBP, resulting in increased immune activation and inflammation, perhaps resulting in HIV disease progression.…”

Macrophage Activation and the Tumor Necrosis Factor Cascade in Hepatitis C Disease Progression Among HIV-Infected Women Participating in the Women's Interagency HIV Study

“…The difference in outcomes is perhaps due to difference in study design, population, or the endpoints defining liver disease progression, or related to the low proportion of patients in the current study that reported hazardous alcohol consumption. Our earlier study included women with heavy alcohol use, and there are some data that alcohol use, itself, without significant liver disease, increases sCD14 levels in HIV-infected persons 40,46 .…”

High prevalence of unhealthy alcohol use and comparison of self-reported alcohol consumption to phosphatidylethanol among women engaged in sex work and their male clients in Cambodia

“…The proportion with PEth positive (≥50 ng/ml) and PEth negative (<50ng/ml) was calculated overall and compared to self-reported alcohol use (AUDIT-C scores). This cutoff has been used to define unhealthy alcohol in the prior three months among HIV-positive patients (Carrico et al, 2015; Hahn et al, 2016). Sensitivity analyses were performed where PEth results were compared to other self-reported measures of alcohol: alcohol frequency, number of drinks on a typical day, being drunk or intoxicated recently, recent heavy episodic drinking, and regular heavy drinking.…”