Wendy T. Robertson

Highly active antiretroviral therapy improves neurocognitive functioning

Summary:Although the effects of highly active antiretroviral therapy (HAART) have resulted in substantial improvements in the systemic health of patients with HIV infection, concerns remain that these medications, which cross the blood–brain barrier poorly, may have a less beneficial effect on nervous system function. This raises the possibility that there may be a progressive long-term decline in neurologic function in patients with adequate systemic response. In a prospective longitudinal study, subjects were evaluated immediately before instituting HAART. Forty-eight subjects underwent ultrasensitive HIV RNA quantitative evaluation of both plasma and cerebrospinal fluid as well as neurologic and neuropsychological examinations. They were reevaluated 6 months after treatment initiation while receiving stable HAART. Both plasma and cerebrospinal fluid viral levels significantly declined after treatment. There was significant improvement in neurologic and neuropsychological functioning after HAART. These results indicate that despite the poor central nervous system penetration of most of these agents, there is satisfactory short-term improvement in both central nervous system viral burden and nervous system function with HAART. However, because treatment failure is increasingly likely over time, continued longitudinal evaluation of this group of subjects is required.

CSF, plasma viral load and HIV associated dementia

Plasma viral burden has proven valuable in predicting the future course of systemic HIV related disease and the response to treatment. It is not known whether plasma or cerebrospinal fluid (CSF) viral burden can be used to predict onset of or response to treatment of nervous system disease. We propose a model of viral load mediated neurotoxicity underlying peripheral and central HIV associated neurological disease. The objective of this preliminary study was to assess the relationship of HIV associated neurological disease to quantitative viral load in plasma and CSF. 47 subjects (HIV- = 10, HIV+ = 37) participated in the study. Plasma and CSF samples were collected within a 3 h window. RT-PCR (Roche Amplicor Monitor) was utilized to assess HIV-1 RNA viral load in both plasma and cell free (centrifuged) CSF. Subjects underwent concurrent comprehensive neurological and neuropsychological evaluations. In general, systemic viral load, as measured in plasma, was greater than that found in cell free CSF. Cell free CSF HIV RNA viral load was significantly correlated with neurological dysfunction, whereas plasma viral load was not. The sole subject with an elevated CSF viral load (> 5 Log 10), had HIV associated dementia (HAD) on clinical examination.

Neurocognitive functioning and HAART in HIV and hepatitis C virus co-infection

Objectives:This study examined the effects of HAART on neurocognitive functioning in persons with hepatitis C virus (HCV) and HIV co-infection. Design:A prospective study examining neurocognitive performance before and after HAART initiation. Method:Participant groups included a mono-infected group (45 HIV+/HCV− participants) and a co-infected group (20 HIV+/HCV+ participants). A neuropsychological battery (attention/concentration, psychomotor speed, executive functioning, verbal memory, visual memory, fine motor, and gross motor functioning) was used to evaluate all participants. After 6 months of HAART, 31 HIV+ mono-infected and 13 HCV+/HIV+ co-infected participants were reevaluated. Results:Neurocognitive functioning by domain revealed significantly worse performance in the co-infected group when compared to the monoinfected group on domains of visual memory and fine motor functioning. Assessment of neurocognitive functioning after antiretroviral therapy revealed that the co-infected group was no longer performing worse than the monoinfected group. Conclusions:The findings of the current study suggest that persons with HCV+/HIV+ co-infection may have greater neurocognitive declines than persons with HIV infection alone. HCV+/HIV+ co-infection may accelerate the progression of HIV related neurocognitive decline.

Timed Gait Test: Normative Data for the Assessment of the AIDS Dementia Complex

The Timed Gait test is a standardized procedure assessing motor dysfunction of lower extremities and gait abnormalities associated with AIDS dementia complex. Heretofore, interpretations of Timed Gait results have been hampered by the lack of normative data. We provide results on this test derived from 1,549 subjects (HIV−seronegatives (HIV−) and seropositives (HIV+) classified according to ADC stage). Timed Gait was found to be a useful screening and assessment tool for evaluating ADC and correlated with clinical ADC staging as well as more extensive structured neurological and neuropsychological evaluations. Analysis of covariance results (with age and education as covariates) revealed symptomatic HIV+(SX) and AIDS groups having significantly slower Timed Gait scores than those in the HIV− and asymptomatic HIV+(ASX) groups. The SX group obtained significantly slower timed gait scores than those in the AIDS group. There was a significant increase in Timed Gait scores with each increase in dementia staging with the HIV− subjects having the fastest mean Timed Gait scores and the HIV+ dementia stage 2+ having the slowest. These normative data should prove useful in both recognition of ADC and treatment response. Given its minimal training requirements, the Timed Gait would have utility in resource limited settings.

Neuropsychologic functioning of human immunodeficiency virus-infected children with hemophilia.

Efforts to detect subtle but objective neuropsychologic deficits could clarify the early involvement of the central nervous system and the progression of human immunodeficiency virus (HIV) infection in older children and young adolescents. Baseline examinations of 63 children and adolescents with hemophilia were conducted by examiners unaware of HIV status or staging or of our studys major hypotheses. They measured six domains of neuropsychologic functioning (motor, language, memory, attention, visual processing, and problem solving), and no differences between groups of similar age, race, and socioeconomic status defined by HIV seropositivity (n = 25) and HIV seronegativity (n = 38) were revealed. A high incidence of subtle neuropsychologic deficits relative to (1) age norms and (2) individual cognitive potential was found on measures of motor performance, attention, and speeded visual processing within both infected and uninfected groups. On the basis of these baseline data, it seems premature to attribute early, subtle neuropsychologic deficits in seropositive children with hemophilia to the central nervous system effects of HIV infection.

No gender differences in the progression of nervous system disease in HIV infection

Summary: The past decade has seen a marked increase in the number of HIV-infected women in the United States. There has been recent concern that HIV disease in general may progress more rapidly in women than men, and some studies, primarily retrospective reviews, have suggested higher rates of neurologic disease among females. The objective of this study was to assess gender differences in HIV-related central and peripheral nervous system disease over time. Participants were enrolled in a longitudinal cohort study at the University of North Carolina and had annual follow-up evaluations. At baseline, 42 HIV-negative females, 52 HIV-positive females, and 52 HIV-positive males were compared for age, education, mode of infection, absolute CD4 cell count, and plasma/cerebrospinal fluid HIV RNA load. Subjects were evaluated by standardized clinical neurologic, neuropsychological, and laboratory examinations every year. The results indicated that both HIV-positive males and HIV-positive females had poorer neurologic functioning than the control group. However, there was no evidence from the parameters measured that the rate of decline differed between HIV-positive males and HIV-positive females.

Psychoimmunology and aids: Psychological distress and herpes simplex virus in human immunodeficiency virus infected individuals

Abstract No studies investigating the relationship of herpesviruses and psychological distress in Human Immunodeficiency Virus (HIV) infection are available in the literature. Antibody titers for Cytomegalovirus (CMV), Epstein-Barr (EBV) and Herpes Simplex virus (HSV) were assessed from sera drawn at the lime of psychological testing for one hundred HIV seropositive subjects. Increased psychological distress was correlated with increased titers of antibody to HSV, but not to CMV or EBV. Psychological distress may play a role in the devastating HSV infections experienced by immune deficient individuals. A stress mediated reactivation/potentiation hypothesis is discussed, where distress reactivates latent HSV which in turn potentiates HIV replication. These results may have implications for treatment of individuals co-infected with HIV and HSV.

Assessing health-related quality of life in NeuroAIDS: Some psychometric properties of the Neurological Quality of Life Questionnaire (NeuroQOL)

Several studies were undertaken to assess the psychometric properties (reliability and initial convergent and discriminant construct validity) of the Neurological Quality of Life Questionnaire (NeuroQOL). The NeuroQOL contains 114 items answered in self report Likert format, with higher scores reflecting better quality of life. Study one compared the questionnaire with existing quality of life measures (Symptom Distress Scale, Sickness Impact Profile) and a significant (p<0.05) correlation was found. Studies two through five evaluated the relationship between the NeuroQOL and disease stage, psychological, neuropsychological and neurological measures, and a significant correlation was also found with each domain. The internal consistency reliability (alpha=0.96), split half reliability (r(12)=0.97), and test-retest reliability (coefficients were 0.78 for 6 months and 0.67 for one year intervals between test and retest) were all found to be high and adequately stable. Overall, these results indicate acceptable reliability and initial construct validity for the NeuroQOL.

The Minnesota Multiphasic Personality Inventory—2 across the Human Immunodeficiency Virus Spectrum

The Minnesota Multiphasic Personality Inventory—2 (MMPI-2) was used to assess individuals’ patterns of psychological symptoms across the spectrum of HIV illness. Two hundred and twenty-five participants in the present sample were administered the MMPI-2, 61 were HIV-seronegative controls, 61 were asymptomatic, 36 were symptomatic, and 67 met criteria for AIDS. Symptomatic HIV-seropositive patients scored higher on the Hypochondriasis, Conversion-Hysteria, and Depression Scales. These differences appeared to be largely due to an increase in somatic complaints rather than an increase in other depressive symptoms. Group differences did not appear to be due to HIV-associated neuropsychological dysfunction. Interpretive strategies for the MMPI-2 and treatment considerations are discussed.