Background:  Progression of liver disease associated with hepatitis C virus (HCV) infection is accelerated in HIV-co-infected persons. Because mortality due to AIDS has decreased substantially since the introduction of HAART, HCV-related mortality is likely to take on a greater significance among HIV-infected injection drug users (IDU) who are almost universally HCV-co-infected. To disentangle the effects of HCV and HIV, we compared mortality from specific causes of death in HCV/HIV-co-infected IDU with that of HCV-mono-infected IDU and IDU without HCV and HIV, before and after the widespread use of HAART.

Methods:  The study population consisted of 1276 IDU from the Amsterdam Cohort Studies that started in 1985. Blood drawn for HIV testing at 4- to 6-monthly visits was retrospectively tested for HCV. We estimated cause-specific hazards ratios (CHR) within and between serologic groups. Causes of death were:  hepatitis or liver-related, AIDS-related, other natural, non-natural, and unknown; 59 HCV and 95 HIV seroconverters switched between serologic groups (time-updated covariate). We evaluated the effect of calendar period, and adjusted for potential confounders, including injection duration and anti-Hbc.

Results:  Serological groups at study entry were: 19% HCV⁺/HIV⁺, 43% HCV⁺/HIV^–, 1% HCV^–/HIV⁺, 36% HCV^–/HIV^–. During follow-up, 272 IDU died. Overall, the risk of dying decreased for most causes of death in the HAART era (reference <1997), but the risk was not the same within serological groups:  for HIV⁺/HCV⁺ IDU, the risk of death from AIDS decreased significantly (CHR 0.37, 95%CI 0.19 to 0.72), whereas the risk of hepatitis or liver-related death did not change over time (CHR 0.87, 95%CI 0.21 to 3.58). In HCV⁺/HIV^– and HCV^–/HIV^– IDU, no significant changes in the risks of dying were seen. When comparing the risks of dying among serologic groups, in the HAART era HCV⁺/HIV⁺ IDU had a significantly higher risk of hepatitis or liver-related death than HCV⁺/HIV^– IDU (CHR 7.15, 95%CI 1.98 to 25.8). Increased risks of dying from non-natural and natural causes of death were also found. No major differences were observed between HCV^–/HIV^– and HCV⁺/HIV^– IDU.

Conclusions:  The risk of dying from HCV-related causes among HCV/HIV-co-infected IDU has not increased after the introduction of HAART. However, compared to HCV⁺/HIV^– IDU, HCV/HIV-co-infected IDU remain at increased risk of hepatitis and liver-related death >1997, suggesting that HIV co-infection continues to accelerate HCV disease progression. Efforts should be made to establish effective HCV treatment in HCV/HIV-co-infected persons.