As hypothesized, HIV/HCV co-infected subjects were more likely to be classified as neuropsychologically impaired than were HIV mono-infected adults. Specifically, co-infected participants were almost three times more likely to be classified as impaired in the domains of learning as well as memory. Although not statistically significant due to power limitations, the co-infected cohort also had slightly higher rates of impairment on measures of psychomotor speed and upper extremity motor speed.
Consistent with our prior work,22
as well as that of others,14,18,19,21
co-infection with both HIV and HCV appears to be associated with an increase risk of cognitive impairment. Several possible explanations can be advanced to explain this finding. Given that the primary route of transmission for HCV is injection drug use, it may simply be that the incremental rate of neurocognitive impairment among the co-infected patients is due to the deleterious effects of drug abuse rather than HCV infection. While this explanation cannot be definitively ruled out, we did exclude all subjects with a DSM-IV diagnosis of current drug abuse in the present study. Since the adverse effects of drug use on cognition typically tend to dissipate over time, it is unlikely that our current findings are due to the effects of historical drug use alone.
There are at least two routes by which HCV could be postulated to cause neuropsychological impairment. First, subjects with decompensated liver disease might have hepatic encephalopathy, which is associated with elevated levels of ammonia.12
Subjects with clinical diagnoses of hepatic encephalopathy were excluded from the current study, but it is possible that some subjects might have had slight or sub-clinical hepatic encephalopathy that contributed to cognitive impairment.27
Alternatively, HCV has been found to invade the nervous system28
and can be recovered from CSF.29
HCV infects monocytes and macrophages, the same cells that are a target of HIV,28
leading us to suspect that similar neuropathogenic mechanisms might be at play.
Alternatively, it may be that the higher rates of neuropsychological impairment among the co-infected subjects are due to the additive, if not synergistic effects of HCV infection superimposed on HIV infection. Previous studies have demonstrated common neurobehavioral symptomatology and common abnormalities on neuroimaging, and have posited a common neurophysiologic mechanism underlying the shared cognitivedeficits. Whether this is due to the direct effects of these viruses on the brain, or an inflammatory cascade triggered by infection, remains to be determined.
Additional research on HIV/HCV co-infection is clearly needed. Such studies will have to give more careful consideration towards controlling for common confounding conditions such as comorbid drug and alcohol abuse. Similarly, different definitions of cognitive “impairment,” often determined by comparison to normative data, might overestimate the potential effects of HCV/HIV co-infection. Ideally, adequately powered studies that include groups of demographically matched healthy controls in addition to mono infected HIV+, mono-infected HCV+, as well as HIV/HCV co-infected subjects will better allow estimation of the potential effects of each virus alone and in combination. Future studies that employ multiple methodologies for assessing brain-behavior function, such as functional and structural neuroimaging in addition to neuropsychological assessment, are likely to be particularly informative.
There are several other practical implications of this study that bear mention. Given the elevated rate of cognitive symptomatology in HCV+ individuals, neuropsychological screening of HCV+ patients, particularly those with more pronounced drug use histories or those who are HIV co-infected, may prove useful in detecting patients with neurocognitive compromise. This may have particular relevance when structuring interventions to improve treatment compliance (such as medication adherence) or in risk-reduction efforts. In this context, risk-reduction should not only focus on drug use behaviors, but also on behavioral practices that may increase transmission of infection such as riskier sexual practices and needle sharing.