Elizabeth Ryan

Interrater Reliability of Clinical Ratings and Neurocognitive Diagnoses in HIV

We examined the interrater reliability (IRR) of clinical ratings of neuropsychological (NP) impairment and neurocognitive diagnoses in HIV. Thirty participants with advanced HIV-infection who were enrolled in a multicenter HIV brain banking research project underwent comprehensive NP and neuromedical evaluations. Using a standardized system of guidelines, neuropsychologists from six participating sites independently assigned clinical ratings of NP impairment, as well as multilevel diagnoses reflecting the inferred etiology of the impairments and their effects on everyday functioning. Findings indicated excellent IRR in rating the presence and severity of NP impairment, but overall modest IRR for neurocognitive diagnoses. Not surprisingly, most diagnostic disagreements concerned the etiology of impairments in persons with medical and neuropsychiatric risk factors in addition to HIV.

Neuropsychiatric impact of hepatitis C on advanced HIV

Objective: To determine whether hepatitis C (HCV) contributes to CNS dysfunction among HIV-infected individuals. Methods: Using a cross-sectional design, the neuropsychiatric profile of individuals with advanced HIV coinfected with hepatitis C (HIV+/HCV+) was compared to similarly advanced HIV patients without HCV coinfection (HIV+/HCV−). Participants were derived from the Manhattan HIV Brain Bank and underwent neurocognitive testing and semistructured psychiatric interviews. Evidence of HCV infection was determined by serology performed prior to study entry. Hepatic function was determined by serum chemistries (bilirubin, creatinine, and international normalized ratio) at the time of the cognitive assessments. Results: Coinfected (HIV+/HCV+) individuals were significantly more likely to have had past opiate or cocaine or stimulant dependence. HIV+/HCV+ participants also had significantly greater rates of past substance-induced major depression. There were no significant differences in rates of primary mental disorders. Forty-two percent of both the HIV+/HCV+ and HIV+/HCV− participants met criteria for current major depression. There was a trend for HIV+/HCV+ patients to perform worse neurocognitively. On tests of executive functioning, HIV+/HCV+ individuals exhibited a greater rate of impairment and had significantly more perseveration. Differences in cognitive functioning were associated with serology but did not correlate with indices of liver disease severity. The HCV+ patients were also more likely to be diagnosed with HIV-associated dementia. Conclusions: There appears to be a neuropsychiatric impact of HCV that is detectable even among an advanced HIV cohort.

Clinicopathologic correlates of hepatitis C virus in brain: A pilot study

Hepatitis C virus (HCV) has been detected in the brain tissues of 10 individuals reported to date; it is unclear what clinical factors are associated with this, and with what frequency it occurs. Accordingly, a pilot analysis utilizing reverse transcriptase-polymerase chain reaction (RT-PCR) to detect and sequence HCV in premortem plasma and postmortem brain and liver from 20 human immunodeficiency virus (HIV)-infected and 10 HIV-naïve individuals was undertaken. RNA encoding the first 126 amino acids of the HCV E1 envelope protein and the majority of the E1 signal sequence was analyzed in parallel with an 80-base-long segment of the 5′ untranslated region (UTR). Liver HCV was detected only in subjects with premortem HCV viremia (10 HIV-infected and 3 HIV-naïve). Brain HCV was detected in 6/10 HCV/HIV-coinfected and 1/3 HCV-monoinfected subjects. In the setting of HIV, the magnitude of plasma HCV load did not correlate with the presence of brain HCV. However, coinfected patients with brain HCV were more often off antiretroviral therapy and tended to have higher plasma HIV loads than those with HCV restricted to liver. Furthermore, premortem cerebrospinal fluid (CSF) analysis revealed that HCV/HIV-coinfected patients with brain HCV had detectable CSF HIV, whereas those without brain HCV had undetectable CSF HIV loads (P = .0205). Neuropsychologic tests showed a trend for hierarchical impairment of abstraction/executive functioning in HIV/HCV coinfection, with mean T scores for HIV monoinfected patients 43.2 (7.3), for liver-only HCV 39.5 (9.0), and for those with HCV in brain and liver 33.2 (5.1) (P = .0927). Predominant brain HCV sequences did not match those of the plasma or liver in 4 of the 6 coinfected patients analyzed. We conclude that in the setting of HIV/HCV coinfection, brain HCV is a common phenomenon unrelated to the magnitude of HCV viremia, but related to active HIV disease and detectable CSF HIV. Furthermore, there is sequence evidence of brain compartmentalization. Differences in abstraction/executive function of HCV/HIV coinfected patients compared to HIV monoinfected warrant further studies to determine if neuropsychiatric effects are predicated upon brain infection.

Effects of hepatic function and hepatitis C virus on the nervous system assessment of advanced-stage HIV-infected individuals

Objectives:To examine the effects of liver function and hepatitis C virus (HCV) serostatus on neurological, neuropsychological, and psychiatric abnormalities in an advanced-stage HIV-infected cohort. Design:A correlational analysis of baseline data accumulated on 137 participants in the Manhattan HIV Brain Bank, a longitudinal study of HIV-infected individuals. Methods:Patients underwent a battery of neuropsychological tests, a semi-structured psychiatric interview, and a neurological examination. The resulting diagnostic data were correlated with biochemical indices of hepatic function and HCV serostatus. Results:Biochemical indices of liver function correlated with motor dysfunction determined by neurological evaluation, but not with neuropsychological or psychiatric disorders. Discrete neurological diagnostic entities showed no relationship with biochemical indices, with one exception: patients with cryptococcal leptomeningitis had worse liver function than those without. HCV had no relationship with any neurological disorder or symptom complex. In contrast, HCV serostatus was related to neuropsychological and psychiatric abnormalities, and indices of liver function were not. HCV-seropositive patients were more likely to have histories of opiate, cocaine or stimulant dependency, to have greater impairment in executive functioning, and to meet diagnostic criteria for AIDS dementia, compared with HCV-negative individuals of similar immunological and virological status. Conclusions:HCV and biochemical indices of liver function associate differentially with nervous system abnormalities in this HIV-infected population. Neurological abnormalities correlate with biochemical indices of liver function, whereas neuropsychological and psychiatric dysfunction are linked to HCV infection. We postulate that multifactorial impacts of HCV and liver disease on HIV-related nervous system disorders may originate in different anatomical and cellular compartments.

Characterization and Sociocultural Predictors of Neuropsychological Test Performance in HIV+ Hispanic Individuals

Hispanic individuals in the U.S. have been disproportionately impacted by HIV/AIDS, yet little is known regarding the neuropsychological sequelae of HIV within the Hispanic population. This study characterized neuropsychological (NP) test performance of HIV+ English-speaking Hispanic participants (n = 51) and investigated the combined roles of sociocultural factors (e.g., ethnicity, socioeconomic status [SES] proxy, and reading level) on NP test performance among our HIV+ Hispanic and non-Hispanic White participants (n = 49). Results revealed that the pattern of NP impairment in HIV+ Hispanic participants is consistent with the frontal-striatal pattern observed in HIV-associated CNS sequelae, and the overall prevalence of global NP impairment was high compared to previous reports with more ethnically homogeneous, non-Hispanic White cohorts. Multivariate prediction models that considered both sociocultural factors and CD4 count revealed that reading level was the only unique predictor of global NP functioning, learning, and attention/working memory. In contrast, ethnicity was the only unique predictor of abstraction/executive functioning. This study provides support for the use of neuropsychological evaluation in detecting HIV-associated NP impairment among HIV+ Hispanic participants and adds to the growing literature regarding the importance of considering sociocultural factors in the interpretation of NP test performance.