Various neuropsychological assessments were performed before antiretroviral therapy was initiated. The Trailmaking and WAIS Digit Symbol tests were used to measure attention, visual-motor coordination, mental flexibility, and information processing speed. The Center for Epidemiologic Studies-Depression Scale (CES-D) was used to assess depression. Results were compared between HIV-monoinfected and HIV/HCV-coinfected participants.
The coinfected participants had significantly lower neuropsychological performance scores overall (p=0.012); in particular, they did less well on the Digit Symbol task (p<0.001). In terms of depression, 52 percent of the coinfected subjects had clinical depression, compared with 33 percent of those with HIV alone. In particular, the coinfected subjects had significantly higher "somatic complaint" scores (p<0.001).
Depression is known to be associated with impaired cognitive function. However, in this study, a multivariate analysis suggested that HCV infection was significantly associated with reduced performance on the Digit Symbol task, even after controlling for depression and other potentially confounding variables such as education level, injection drug use, alcohol use, hepatitis B status, CD4 count, and HIV viral load. Although the coinfected subjects had higher ALT and AST, levels were not exceedingly high, and the types of cognitive impairment seen did not resemble the profile of hepatic encephalopathy.
The investigators concluded that HIV/HCV coinfection adversely affects neuropsychological performance and may also be associated with depressed mood.
Researchers assessed 130 HIV-positive adults in Baltimore (USA) and Melbourne (Australia), two populations selected for their contrasting demographic profiles. Pain assessment and sensory testing (thermal and vibration) was done, mitochondrial DNA in subcutaneous fat was quantified, and punch skin biopsies were evaluated for the presence of peripheral nerve damage.
Among the 47 Baltimore subjects, 78 percent were male, 83 percent were African American, the primary HIV risk factor was injection drug use (70 percent), the mean CD4 count was 289 cells/mL, and 71 percent were coinfected with HCV. Among the 83 participants in Melbourne, 96 percent were male, 95 percent were white, the primary HIV risk factor was male/male sex (92 percent), the mean CD4 count was 356 cells/mL, and the HCV seroprevalence rate was only 11 percent. In Baltimore, about 80 percent were on antiretroviral therapy at baseline, compared with 90 percent in Melbourne. Known neurotoxic NRTIs -- ddC, ddI, and/or d4T -- were used by a substantial portion of both groups (somewhat higher use was reported in Melbourne).
At baseline, more than half of the subjects in both groups (52 percent in Baltimore, 56 percent in Melbourne) had symptomatic peripheral neuropathy; 17 percent in Baltimore and 7 percent in Melbourne had asymptomatic neuropathy; and 30 percent and 36 percent, respectively, did not have neuropathy. However, skin biopsies from a subset of the Baltimore subjects indicated that half of the "neuropathy-free" patients had evidence of morphological nerve abnormalities (changes in nerve structure and appearance). As expected, sensory neuropathy was strongly associated with use of the neurotoxic NRTIs, particularly for a duration of more than one year.
In this analysis, HCV was not significantly associated with a greater risk of peripheral neuropathy in HIV-infected subjects. Likewise, age, CD4 count, plasma lactate or B12 levels, and mitochondrial DNA in subcutaneous fat were not associated with baseline higher rates of neuropathy. The researchers concluded that hepatitis C serostatus did not appear to modify the prevalence of sensory neuropathy or nerve morphology in this cross-sectional analysis.
Editor's Note: Reprinted with permission from www.aidsmap.com (first e-published February 14, 2004).