Both injection drug use (IDU) and hepatitis C (HCV) coinfection nearly tripled the risk of death in HIV-positive North Americans and Europeans, according to a large antiretroviral therapy cohort collaboration (ART-CC) study. But statistical analysis showed that HCV infection drove the heightened death risk in IDUs.
Decades of research and clinical experience establish worse survival among people infected with HIV while injecting drugs than in people infected by other routes. Sorting out which factors contribute most to the heightened death risk in IDUs remains challenging because of the multiple behavioral and clinical variables that may affect mortality in this population. Because many HIV-positive IDUs are coinfected with HCV, the hepatitis virus ranks among the leading mortality-cofactor candidates.
To determine the relative impact of IDU and HCV on mortality in contemporary HIV populations, ART-CC researchers examined data on members of 16 European and North American cohorts who started antiretroviral therapy between 2000 and 2009. They estimated mortality hazard ratios for IDU (versus non-IDU) and HCV (versus HCV negative) after adjustment for age, sex, AIDS diagnosis before antiretroviral therapy, and baseline CD4+ cell count and HIV RNA (viral load).
The analysis included 32,703 antiretroviral-treated people: 3374 (10.3%) of them IDUs and 4630 (14.2%) HCV positive. About two-thirds of cohort members were men. Among IDUs, 85% had HCV infection. Median age stood at 37 years in people without HCV and 39 in those with HCV. Within three years of starting antiretroviral therapy, 1116 people (3.4%) died).
Cox proportional hazards models determined that IDUs had almost a tripled risk of death compared with non-IDUs (adjusted hazard ratio [aHR] 2.71, 95% confidence interval [CI] 2.32 to 3.16), as did HCV-coinfected people compared with HCV-negative individuals (aHR 2.65, 95% CI 2.31 to 3.04). Adjustment for IDU only modestly attenuated the impact of HCV infection on mortality (aHR 2.04, 95% CI 1.68 to 2.47). But HCV substantially attenuated the impact of IDU on mortality (aHR 1.57, 95% CI 1.27 to 1.94).
Both IDU and HCV boosted risk of liver-related mortality more than 10-fold (aHR 10.89 for IDU and 14.0 for HCV). Adjustment for HCV greatly attenuated the impact of IDU on liver death (aHR 2.43), whereas adjustment for IDU had a smaller impact on the HCV-associated risk of liver death (aHR 7.97). These associations indicate that HCV coinfection explains a large proportion of the excess mortality observed in antiretroviral-treated IDUs.
The ART-CC team believes their findings "underscore the importance of overcoming these barriers [to HCV therapy] if we are to achieve better survival among those aging with HIV, many of whom no longer use injection drugs but are continuing to suffer consequences of past use." They add that an HCV coinfection epidemic is also emerging among HIV-positive men who have sex with men, who could also benefit from the new direct-acting antiviral HCV regimens.
Mark Mascolini is a freelance writer focused on HIV infection.