Background:  HIV-1 and HCV cause neurologic complications but it is unclear whether HIV and HCV interact. We evaluate the effect of HCV/HIV co-infection on neuropsychological performance and depression in ARV- and anti-HCV treatment-naïve subjects.

Methods:  A5097s is a substudy of A5095, a phase 3 antiretroviral treatment protocol for treatment-naïve HIV-infected subjects.  We evaluated the populations at baseline before any therapy was initiated. Neuropsychological performance tests included Trailmaking Test (parts A and B) and the Digit Symbol task, which together assess attention, speed of information processing, and mental flexibility. Depression was assessed with the Center for Epidemiologic Studies-Depression Scale (CES-D). HCV status was determined by the presence of anti-HCV antibody at entry. For each subject, a baseline z-score was calculated for each subtest, representing the number of standard deviations  away from an age-adjusted normative performance. The results were compared between the HCV/HIV-co-infected and the HIV-infected only groups.

Results:  Of patients enrolled in A5097s, 235 had HCV status data available at entry (25 HCV⁺ and 210 HCV^-). The HCV⁺ and HCV^- groups were comparable except that the HCV⁺ group had higher prevalence of history of IV drug use and lower educational level (p <0.05).  The HCV⁺ group had significantly lower Z-scores in neuropsychological performance overall, (0.69 vs 0.13 SDs below the mean, p=0.012). Among 3 subtests, the HCV⁺ group performed less well than the HCV^- group on the Digit Symbol task, (0.92 vs 0.21 SDs below the mean, p<0.001). Multivariate modeling suggests that there is a significant relationship between HCV-infection status and performance in the Digit Symbol task even when controlling for confounding variables (education, sex, IV drug use, CD4 count, HIV-1 RNA, depression, alcohol use, and hepatitis B status). Of the HCV⁺ subjects 52% and  of HCV^- subjects 33% had significant depression (p=0.055). Group differences resulted from significantly higher scores on the “somatic complaint” portion of the CES-D scale (p<0.001).

Conclusions:   Our findings suggest that HCV/HIV co-infection adversely affected neuropsychological performance, particularly in the Digit Symbol task. HCV may also be associated with depressed mood particularly with somatic complaint. Despite a limited sample size and the difficulty of excluding all possible confounding factors, our results control for many potential confounds while still demonstrating a probable effect of hepatitis C on neuropsychological performance.

Keywords: neuroAIDS; hepatitis C; neuropsychologic performance