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HCV/HIV Coinfection May Cause Depression & Cognitive Dysfunction Compared to HIV Monoinfection
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HCV Infection May Cause Depression & Cognitive Dysfunction
Reported by Jules Levin
"Hepatitis C and Neuropsychological Function In Treatment Naive HIV-1-infected Subjects - A5097s Baseline Analysis"
Y Yang1, S Evans1, R Gulick2, D Clifford*3, and AIDS Clinical Trials Group A5097s Team 1Harvard Sch. of Publ. Hlth., Boston, MA, USA; 2Weill Med. Coll. of Cornell Univ., New York, NY, USA; and 3Washington Univ. Sch. of Med., St. Louis, MO, USA
Researchers from the AIDS Clinical Trials Group (ACTG) reported study results from an analysis of a substudy within a larger ACTG study at the 11th Retrovirus Conference (Feb 8-11, 2004, San Francisco). They found what myself and others have known that infection with hepatitis C can cause for many individuals, not necessarily all, cognitive dysfunction. We know that HIV itself may cause cognitive disfunction for some individuals infected with HIV. There was a study at CROI suggesting that despite successful HAART (undetectable HIV RNA, <50 copies/ml) cognitive dysfunction may persist for some patients. These results were controversial with not all observers accepting this and there was some question about the testing methodology used in this study. Nonetheless, I think that some individuals with <50 copies/ml and good CD4 counts on HAART may still have some cognitive dysfunction, but this has not yet been adequately studied. All of this does suggest that HCV & HIV coinfected patients may suffer with greater cognitive dysfunction and depression than HIV monoinfected individuals and more than HCV monoinfected individuals. It is pretty well accepted that individuals with past or current substance abuse problems may suffer from depression and cognitive dysfunction more than due to HIV-infection. Some individuals experience depression merely upon learning they have HCV. SO, the question addressed by the study presented at CROI—was do HCV/HIV coinfected patients experience more cognitive dysfunction and depression than HIV monoinfected individuals and is it due to the HCV and/or other things such as prior substance abuse and other social ills.
This study evaluates the effect of HCV/HIV co-infection on neuropsychological performance and depression in ARV- and anti-HCV treatment-naïve subjects.
Patients in the study were given a battery of tests. The researchers reported that HCV/HIV coinfected patients performed less well than HIV monoinfected individuals on tests evaluating attention, speed of information processing, and mental flexibility. Of note, researchers found these results when controlling for—in other words, they said these factors did not contribute to a poorer response by coinfected patients: education, sex, IV drug use, CD4 count, HIV-RNA, depression, alcohol use, and hepatitis B status. Researchers also found that the coinfected patients were more likely to experience depression than HIV monoinfected patients (52% vs 33%), by using a test to evaluate this question. You can read the author's conclusions below where they say "probably" coinfected patients experience worse neurological performance & depression than HIV moninfected individuals and that having hepatitis C is the reason. They say "probably" because although they tried to account for the confounding factors such as education, substance abuse, and other things, it is difficult to absolutely rule out their effect, and the study size was not large. Still, numerous studies find that some individuals do experience deficits in neurologic performance, cognitive dysfunction, and depression due just to having HCV. Studies also show that following successful therapy for HCV with interferon plus ribavirin, achieving a sustained viral response (undetectable 6 months after stopping therapy) can improve depression and neurologic performance. I can confirm this from my personal experience. I successfullu completed peginterferon/ribavirin therapy and maintain undetectable HCV viral load 2 years after stopping therapy. Immediately after stopping therapy with an undetectable viral load I noticed a sharp improvement in my energy and mental functioning. This improvement has continued to improve even more as time has gone by. I have much more energy and mental clarity than before I completed HCV therapy successfully.
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.
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).
The study authors concluded that 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.
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