Background: Alcohol consumption is common in HIV infected women. Heavy alcohol consumption has been associated with accelerated HIV disease progression and poor health outcomes, mainly attributed to inadequate antiretroviral adherence. We hypothesized heavy alcohol consumption alters macrophage activation and inflammation and independently influences HIV disease progression.
Methods: Women’s Interagency HIV Study (WIHS) participants who were hepatitis C seronegative were stratified into 4 groups: HIV+ and HIV- with the heaviest chronic alcohol consumption and abstainers, 50/group. Participants were matched on age, race, and education. Soluble macrophage activation marker (sCD163) and sTNF-RII, a marker of inflammation/activation, were measured using ELISA in a subset of n=25/group at 4 time points over 10 years (2001-11). ANOVA was used to examine differences between groups in soluble markers and multivariable random effects logistic and random linear regression models examined associations.
Results: Across the study period, drinkers reported a mean of 21 drinks/week. Adjusting for HAART use, duration and self-reported adherence, HIV+ heavy drinkers (> 7 drinks/week) were more likely to have a CD4 count<350 cells/mm3 (OR=3.67, p=.005) and detectable viral load (OR=1.65, p=.051) than non-drinkers. sCD163 (mean ng/mL + sd) at baseline was highest in HIV+ drinkers 2098 (1582) compared to HIV+ abstainers 1355 (743), HIV- drinkers 1216 (551), and HIV- abstainers 1349 (673) (F=10.61, p<.001). sTNFRII expression at baseline (mean pg/mL + sd) was higher in both HIV+ drinkers 2692 (889) and HIV+ abstainers 2659 (1093) compared to HIV- drinkers 1697 (557) and HIV- abstainers 1893 (451) (F=4.21, p=.008). Both sCD163 & TNFRII did not significantly change over time. In multivariable longitudinal models, HIV+ drinkers had significantly higher sCD163 than other groups (p<.001); both HIV+ drinkers and HIV+ abstainers had significantly higher sTNFRII than HIV- women (p<.001 and p=.006 respectively). Among HIV+ women, both sCD163 & sTNFRII were significantly associated with elevated viral load (sCD163, p<.001; sTNFRII, p=.021) over time; sTNFRII was associated with lower CD4 cell counts (p=.001).
Conclusions: Chronic heavy drinking is independently associated with HIV outcomes (CD4+ count and viral load). Persistently elevated level of sCD163 in HIV+ve heavy drinkers suggests a mediating role of macrophage activation with implications to persistent inflammation in HIV-infected women reporting heavy alcohol consumption.