Background:  Injection drug users (IDU) experience significant morbidity and mortality related to HIV and hepatitis C virus (HCV) infection. Data are limited with respect to predictors of progressive liver disease among IDU infected with both viruses. We examined the effect of viral and nonviral factors on the rate of liver disease progression and liver-related mortality in a cohort of HIV/HCV-co-infected drug users.

Methods:  We performed a prospective analysis of liver-related events (i.e., clinical progression of, or death from, liver disease) in 231 HIV/HCV-co-infected IDU enrolled in the Hepatitis C, HIV, and Related Morbidity (CHARM) study cohort, who had at least 1 year of follow-up between August 2002 and January 2004. Cox regression analysis was used to estimate hazard ratios (HR) for demographic (gender, age, race), HCV (age at infection, viral load), HIV (nadir CD4, viral load, ART), hepatitis B virus (HBV) carrier status, and current substance abuse (injection drug use, hazardous drinking) variables.

Results:  Of the total 22 HIV/HCV-co-infected subjects experienced liver-related events, at a rate of 5.1/100 person-years. Statistically significant univariate predictors of increased liver disease progression or death included Hispanic race (HR = 5.2; 95% CI 1.1 to 24.3) and nadir CD4 < 100 (HR = 15.8; 2.0 to 122); ART with viral load < 75 (copies/mL) was associated with a significant decreased rate (HR = 0.29; 0.08 to 1.00). The effect of black race (HR = 3.1; 0.69 to 13.8), nadir CD4 100 to 199 (HR = 7.4; 0.86 to 63.0), and current injection drug use (HR = 1.9; 0.80 to 4.6) were of borderline significance. Neither age at HCV infection, HBV infection, nor current hazardous drinking (AUDIT score ≥ 8) predicted liver disease progression. In multivariate analysis, nadir CD4 < 200 (< 100, HR = 19.1; 2.1 to 177; 100 to 199, HR = 10.9; 1.2 to 101) was significantly associated with liver disease progression or death; ART and non-white race also appeared to be strong predictors of the rate of liver-related events.

Conclusions:  Liver-related morbidity and mortality occurred primarily among persons of non-white race in this urban, IDU cohort. The results demonstrate that low nadir CD4 count strongly predicts HCV-related liver disease progression and death in IDU with HIV co-infection. Moreover, receipt of ART may significantly reduce morbidity. Strategies to increase availability of and adherence to ART may decrease progression of HCV liver disease among HIV co-infected IDU.

Keywords: hepacivirus; liver disease; prospective studies