Abstract and Introduction
Abstract
Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001–2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1–20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1–20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08–1.29) for 0.0 g/day and 1.84 (1.62–2.09) for >20.0 g/day compared with 0.1–20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86–1.17) for 0.0 g/day and 1.64 (1.33–2.02) for >20.0 g/day compared with 0.1–20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.
Introduction
Mortality is higher among persons with HIV (PWH) who also have hepatitis C virus (HCV) than those who do not.[1,2] This is despite early administration of combination antiretroviral therapy (ART) and durable suppression of HIV replication having improved overall survival and delayed disease progression among PWH.[3] In some settings, liver-related mortality has been ranked as a leading cause of mortality among PWH,[4–7] likely due to hepatic decompensation and/or hepatocellular carcinoma.[8–10]
Since the advent of direct acting antiviral (DAA)-based treatment in 2014, sustained virological response (SVR) rates are >90% in HIV/HCV co-infected patients,[11–13] who were on the priority list for DAA initiation soon after their arrival on the market. DAA treatment is now recommended for all persons with HCV.[14] Lifestyle factors, especially risk behaviours, are likely to differ between PWH with and without HCV; the prevalence of HCV among PWH with histories of injecting drug use (IDU) is estimated to be 82%.[15] Furthermore, HCV is frequent (weighted average 16.3%) among patients with alcohol use disorders.[16] Alcohol use in PWH with HCV has been related to increased risk of liver disease progression (liver fibrosis, liver cancer and liver-related mortality),[17,18] and no safe level of alcohol use has been described. Excess mortality in PWH with HCV could be addressed by interventions to reduce harm from substance/alcohol use and other risk behaviours. However, data on the association of alcohol use with all-cause and cause-specific mortality in PWH with HCV are scarce, especially in the era of DAAs.
Studies of alcohol use among PWH have found J- or U-shaped associations with mortality: those with no alcohol use and heavy alcohol use have higher mortality than those with low/moderate alcohol use.[19] Higher mortality among non-drinkers may arise because some members of this group stopped drinking due to illness or alcohol dependency.[20,21] Whether the same patterns holds among PWH with HCV is unclear.
We aimed to investigate whether the association between alcohol use and all-cause mortality in PWH differed by HCV status, and whether any such difference remained after accounting for HCV cure. We then investigated these outcomes in separate follow-up periods to account for the availability of DAAs and assessed trends in all-cause and cause-specific mortality in groups of PWH defined by HCV and alcohol use.
J Viral Hepat. 2023;30(9):775-786. © 2023 Blackwell Publishing
