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HCV Worsens HIV's Neuropsychiatric Impact
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AIDS: Volume 18(13) 3 September 2004
Crabb, Charlene
Both HIV and hepatitis C virus (HCV) can trigger a suite of behavioral and neurological problems that range from fatigue, depression, and slowed thought processing to, in the case of advanced HIV infection, a constellation of symptoms known as HIV-1 dementia complex. Now, researchers at Mount Sinai Medical Center in New York have found that HCV worsens the impact of HIV on the central nervous system. ''It looks like the two are a bad combination,'' says neuropsychologist Elizabeth Ryan, lead author of the study (Neurology 2004, 62:952-962).
Approximately one in three HIV-positive individuals is co-infected with HCV. However, relatively little is known about how either virus, on its own, undermines the brain. Once HIV has filtered through the blood-brain barrier, it tends to settle in the subcortical parts of the brain, such as the basal ganglia-areas that through their connection to the frontal lobe mediate problem solving, emotion and cognitive flexibility as well as voluntary movement. HCV and liver disease, a common manifestation of long-term HCV infection, are both associated with significant neuropsychiatric dysfunction similar to those seen with HIV. ''The two viruses seem to be working on the same circuitry,'' says Ryan. ''So we wondered if people infected with both viruses would have worse cognitive profiles than those who had just HIV.''
To find out, Ryan and her colleagues used a battery of neuropsychological tests, medical analyses, psychiatric interviews and neurologic examinations to evaluate 116 people enrolled in the Manhattan HIV Brain Bank. All the participants, whose average age was 43.7 years, had advanced HIV disease. Sixty-seven of them were also infected with HCV.
The researchers found that more than half of the individuals in both groups tested well below normal in several neuropsychological domains. However, there was an overall trend for co-infected patients to perform more poorly. A slightly greater percentage of HCV-positive patients scored 1.5 or more standard deviations below published norms for psychomotor speed, working memory, verbal fluency, as well as learning and memory retrieval. In the domain of executive functioning, which includes problem solving and hypothesis testing, the difference was significant: 43% of participants with both HIV and HCV scored 1.5 or more standard deviations below the norm compared to 29% of those who were HCV free. Co-infected patients were also more likely - 46% versus 10% - to meet the criteria for HIV-1-associated dementia.
The researchers doubt that liver disease contributed to the differences. The liver function of each participant was assessed using an evaluation designed to prioritize the waiting list of liver transplant patients. No significant differences were found.
Likewise, substance abuse was also ruled out as a cause for the dissimilarities. In general, HCV (and co-infected) patients tend to be substance users. Since substance use affects cognitive functioning, users tend to score more poorly on neuropsychiatric tests. Not surprisingly, Ryan and her colleagues found a clear difference in injecting drug use among the study participants-of the HIV/HCV group, 81% had past opiate dependence compared to 27% in the HIV-only group. However, the researchers found no difference in cognitive functioning between patients with and without a past history of opiate dependence. Nor was past opiate dependence a predictor of greater perseveration, the multiple repetition of words or actions that is symptomatic of many neurological disorders, whereas co-infection was.
Ryan says the study would have been ''a more powerful analysis'' if information about the HCV levels of each co-infected patient had been available. ''All that we had was evidence of HCV serum antibodies in the patients,'' she says. ''We didn't know how much virus they had actively present.'' However, she has received funding for a new study that will evaluate the neuropsychiatric profiles of co-infected patients based on HCV viremia.
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