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Due to overlapping transmission routes, many people are coinfected with both HIV and HCV. HIV-positive people with hepatitis C experience faster liver disease progression than HIV-negative people, but the impact of HCV on HIV disease progression and mortality is not fully understood. Research has shown that HIV-positive people who inject drugs have a higher risk of death than non-injectors, but it is not known how much of this excess risk may be attributable to HCV.

Margaret May from the University of Bristol and fellow investigators analyzed data from more than 32,700 people with HIV in 16 North American and European cohorts who started antiretroviral therapy (ART) between 2000 and 2009.

About 70% of study participants were men and a majority were in the 30-39 or 40-49 year age range. The median baseline CD4 T-cell count was just over 200 cells/mm³ and nearly a quarter had an AIDS diagnosis before starting ART. A total of 3374 had a history of injection drug use (10% overall; 62% of those with HCV and 2% of HCV-uninfected), while 4630 had HCV (14% overall; 85% among drug injectors).

The researchers determined mortality hazard ratios (HRs) for drug injectors versus non-injectors and for people with and without HCV coinfection over a 3-year follow-up period, adjusting for age, sex, baseline CD4 count, baseline HIV viral load, and history of AIDS diagnosis.

Results

• A total of 1116 study participants (3.4%) died during follow-up. 
• Mortality was more than 2.5-fold higher for injection drug users compared with non-injectors (adjusted HR 2.71).
• HIV/HCV coinfected people also had higher mortality compared to those with HIV alone (adjusted HR 2.65). 
• After taking HCV status into account, injection drug use had an attenuated effect on mortality (adjusted HR 1.57).
• Taking injection drug use into account also attenuated the effect of HCV coinfection, but not as much (adjusted HR 2.04). 
• For most specific causes of death, mortality was higher for injection drug users compared with non-injectors, and for coinfected people compared to those with HIV alone.
• Both injection drug use and HCV were strongly associated with liver-related mortality, raising the risk by more than 10-fold (adjusted HR 10.89 and 14.0, respectively).
• After adjusting for HCV status, people who inject drugs remained at elevated risk of mortality due to central nervous system conditions, respiratory conditions, and violent deaths.

"A substantial proportion of the excess mortality in HIV-infected [injection drug users] is explained by HCV coinfection," the study authors concluded. "These findings underscore the potential impact on mortality of new treatments for HCV in HIV-infected people."

"Although there is a growing consensus on the importance of treating HCV coinfection among those living with HIV, many barriers remain," they wrote in their discussion. "Our analyses underscore the importance of overcoming these barriers 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.

"This revolution in treatment of HCV could enable increased treatment uptake, not just among [injection drug users], but also in the emerging [men who have sex with men] epidemic, which could have a major preventative impact," they added. "However, treatment costs may limit scale-up as new drugs are expensive."

7/3/15

Reference

MT May, AC Justice, K Birnie, et al. Injection Drug Use and Hepatitis C as Risk Factors for Mortality in HIV-Infected Individuals: The Antiretroviral Therapy Cohort Collaboration.Journal of Acquired Immune Deficiency Syndromes 69(3):348-354. July 1, 2015.