Study Examines Effects of Alcohol, HIV, HCV on Immune System Activation

Alcohol use among people living with HIV (PLWH) may exacerbate inflammation and immune activation, especially among those coinfected with hepatitis C virus (HCV), according to a study from Alcoholism: Clinical and Experimental Research.

While both HIV and heavy alcohol consumption were previously known to independently promote inflammation and microbial translocation, the impact of alcohol consumption on those processes among PLWH was unclear. This study examined how biomarkers of microbial translocation and innate immune activation were affected by HIV status, HCV co-infection, and alcohol use. The study was conducted to test the hypotheses that PLWH would have higher levels of these biomarkers than HIV-negative individuals with comparable alcohol use and that alcohol use would exacerbate biomarker elevations in HIV-positive individuals.

“Mounting evidence implicates heavy alcohol use as a cause of microbial translocation and immune dysregulation in the general population. Because 47% of PLWH in the United States reported alcohol use and 15% reported heavy drinking in the past 30 days, there is clear potential for alcohol to exacerbate immune dysfunction in the context of HIV. A recent study showed that even moderate drinking, averaging 1 drink per day, was associated with significantly increased mortality in men living with HIV. Some harmful effects of alcohol in PLWH may be mediated by behavioral factors such as decreased adherence to ART [antiretroviral therapy],” researchers said.

Participants for the study were recruited from an immunology clinic that specialized in HIV treatment. Candidates underwent chart review and were screened. PLWH who were nondrinkers or reported moderate or heavy drinking behaviors were recruited based on their medical records and clinical interviews with researchers. HIV-negative individuals who received treatment at the clinic were also recruited for the study’s control group.

In the study, participants classified as nondrinkers reported consumption of 0 drinks, female participants classified as moderate drinkers reported consumption of 7 or less drinks per week while men classified as moderate drinkers reported consumption of 14 or less drinks per week, and both women and men classified as heavy drinkers respectively reported consuming more than 7 or 14 drinks per week.

Study participants were aged between 21 to 70 years and had their HIV serostatus documented by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot and plasma HIV RNA tests. All participants also must have been able to provide plasma samples and behavioral data.

The study included a total of 109 participants; 75 were infected with HIV and 34 were uninfected. All participants were assessed at 3 visits over a period of 5 years. HIV-infected participants were also tested for HCV. The average time between assessments was 18 months. A total of 167 plasma samples were collected from all participants and were available for analysis.

Researchers used the Timeline Followback Interview (TLFB) to assess alcohol and drug use within the last 90 days. The TLFB asked participants to report the number of standard alcoholic drinks they consumed each day and whether they used marijuana, opioids, cocaine, hallucinogens, stimulants, and sedatives. Those determined to have substance use disorder for cocaine, stimulants, heroin, opioids, or any intravenous drug were excluded from the study. Diagnosis of alcohol use disorder (AUD) was determined using the Mini-International Neuropsychiatric Interview (MINI). Participants determined to have remote AUD met the criteria for lifetime but not current AUD. Researchers also used the MINI to evaluate whether participants had substance use disorders. Participants self-reported use of cigarettes.

Researchers collected behavioral data and blood samples during visits. Plasma was isolated from blood samples. ELISAs tested plasma to quantify lipopolysaccharides (LPS), a biomarker of microbial translocation, as well as biomarkers of immune activation, including lipopolysaccharide binding proteins (LBP), soluble CD14 (sCD14), and soluble CD163 (sCD163).

Researchers examined biomarker values by HIV status. HIV infection was associated with significant elevations on all biomarkers. Gender was associated with LBP and sCD14; women had significantly higher concentrations than men. Women were also found to have higher LPD and sCD163 than men at trend level. Older age was associated with lower LPS; the number of cigarettes used per day was positively associated with LBP.

Associations between alcohol use and HCV status with biomarkers in PLWH were examined. Greater alcohol use was associated with higher sCD163 but not for other biomarkers The main effect of HCV coinfection was also significant for sCD163 but was found not to be significant for LBP, LPS, or sCD14. The interaction of alcohol use with HCV coinfection was significant for each biomarker

Researchers found that plasma biomarkers of microbial translocation and immune activation were significantly higher in PLWH compared to those without HIV; they said the study provided new evidence for their hypothesis that alcohol use in the context of HIV infection exacerbates inflammation and immune activation. Their hypothesis was boosted by the interaction of current drinking with HCV coinfection. While alcohol use alone wasn’t significantly associated with most biomarkers in PLWH, the interaction between alcohol use with HCV coinfection was associated with significant elevations on all biomarkers.

Researchers suggested that efforts should focus on reducing alcohol use among PLWH, especially those coinfected with HCV, as alcohol-related elevations in biomarkers sCD163 and sCD14 have been associated with all-cause mortality among PLWH.

Reference

Monnig MA, Cohen R, Ramratnam B, McAdams M, Tashima K, Monti PM. HIV infection, HCV coinfection, and alcohol use: associations with microbial translocation and immune activation. Alcohol Clin Exp Res. 2019;1-9. doi: 10.1111/acer.14032.