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.

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.

Better quality of life with neuropsychological improvement on HAART.

BACKGROUND: Successful highly active antiretroviral therapy (HAART) regimens have resulted in substantial improvements in the systemic health of HIV infected persons and increased survival times. Despite increased systemic health, the prevalence of minor HIV-associated cognitive impairment appears to be rising with increased longevity, and it remains to be seen what functional outcomes will result from these improvements. Cognitive impairment can dramatically impact functional ability and day-to-day productivity. We assessed the relationship of quality of life (QOL) and neuropsychological functioning with successful HAART treatment. METHODS: In a prospective longitudinal study, subjects were evaluated before instituting HAART (naïve) or before changing HAART regimens because current therapy failed to maintain suppression of plasma viral load (treatment failure). Subjects underwent detailed neuropsychological and neurological examinations, as well as psychological evaluation sensitive to possible confounds. Re-evaluation was performed six months after institution of the new HAART regimen and/or if plasma viral load indicated treatment failure. At each evaluation, subjects underwent ultrasensitive HIV RNA quantitative evaluation in both plasma and cerebrospinal fluid. RESULTS: HAART successes performed better than failures on measures exploring speed of mental processing (p < .02). HAART failure was significantly associated with increased self-reports of physical health complaints (p < .01) and substance abuse (p < .01). An interesting trend emerged, in which HAART failures endorsed greater levels of psychological and cognitive complaints (p = .06). Analysis between neuropsychological measures and QOL scores revealed significant correlation between QOL Total and processing speed (p < .05), as well as flexibility (p < .05). CONCLUSION: Our study investigated the relationship between HIV-associated neurocognitive impairment and quality of life. HAART failures experienced slower psychomotor processing, and had increased self-reports of physical health complaints and substance abuse. Contrariwise, HAART successes experienced improved mental processing, demonstrating the impact of successful treatment on functioning. With increasing life expectancy for those who are HIV seropositive, it is important to measure cognitive functioning in relation to the actual QOL these individuals report. The study results have implications for the optimal management of HIV-infected persons. Specific support or intervention may be beneficial for those who have failed HAART in order to decrease substance abuse and increase overall physical health.

Neuroimaging in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV) is associated with central nervous system (CNS) changes that may affect cerebral blood flow (CBF), metabolism, structure, and diffusion. Each of the available neuroimaging techniques offers unique insight into the neural mechanisms underlying HIV, as well as a potential means of monitoring disease progression and treatment response. The purpose of the article is to provide a review of experimental studies evaluating changes related to HIV with imaging techniques, including single-photon emission computed tomography (SPECT), positron emission tomography (PET), volumetric magnetic resonance imaging (MRI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and perfusion MRI (pMRI).

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.

Effects of antiretroviral therapy on cognitive impairment.

Since the introduction of combination antiretroviral therapy, the manifestations of HIV-associated central nervous system (CNS) involvement have generally become less severe and more manageable. Patients initiating antiretroviral therapy have demonstrated improvement in cognitive functioning. Reduction of viral burden has been correlated with improved CNS functioning. Recent studies have focused on the importance of CNS-penetrating antiretroviral regimens to target active replication in this protected compartment. There were initial conflicting reports of whether CNS-penetrating antiretrovirals improved cognitive functioning, with more evidence supporting the importance of CNS penetration in reducing viral burden and improving cognitive outcomes. Cognitive loss remains a feature of HIV infection, and some patients still suffer from incident or progressing cognitive and motor dysfunction even on combination therapy. Because the virus enters the CNS within days of initial infection, latent infection may be chipping away at the brain during the long asymptomatic period in HIV. When to start antiretrovirals for the maximum cognitive benefit remains to be determined.

Assessment of neuroAIDS in the international setting.

The global burden of the HIV epidemic is staggering, but in the short term, it is largely unfelt in the developed world. Almost one million people have been infected with HIV in North America, and the results of effective antiretroviral therapy have dramatically improved survival and quality of life. However, there are 25 million infected in sub-Saharan Africa alone, and antiretroviral treatment is scarce. Ninety-five percent of new infections occur in the developing world where resources are limited. Very little is known about NeuroAIDS in the developing world where few studies have been conducted on the neurologic and neurocognitive effects of antiretroviral treatment. HIV Clade differences and other factors could have dramatic effects on treatment effectiveness. There are a number of barriers in the assessment of neurological and neurocognitive effects in resource limited settings and some of these will be addressed.

Impact of human immunodeficiency virus (HIV) subtypes on HIV-associated neurological disease.

Among the many variables affecting transmission and pathogenesis of the human immunodeficiency virus type 1(HIV-1), the effects of HIV subtypes, or clades, on disease progression remain unclear. Although debated, some studies have found that the variable env and pol sequences of different subtypes of HIV-1 may endow some subtypes with greater degrees of cell tropism, virulence, and drug resistance, which may lead to differences in overall disease progression. HIV-associated dementia (HAD) appears to be associated with viral diversity and markers of immune activation. Africa has the highest prevalence of HIV, largest viral diversity, and is where clade recombination occurs most frequently. All of these factors would suggest that HAD would pose the largest threat in this region of the world. Although investigations into the effects of different subtypes on overall disease progression are well documented, few have looked into the effects of subtypes on neurological disease progression. This review highlights the need for more international research involving the neurological effects and especially the clinical presentation of dementia for the entire range of the group M HIV-1 subtypes.

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.

Cerebrospinal fluid from human immunodeficiency virus--infected individuals facilitates neurotoxicity by suppressing intracellular calcium recovery.

Neurologic decline associated with penetration of human immunodeficiency virus type 1(HIV-1) into the central nervous system is thought to be due, in large part, to inflammation and local secretion of neurotoxic substances. To examine the cellular processes that mediate neurotoxicity in vivo, the authors valuated the ability of neurons to maintain intracellular calcium homeostasis in the presence of toxic cerebrospinal fluid (CSF) (CSF(tox)) collected from a subset of HIV-infected individuals. Exposure of rat neural cultures to CSF(tox) resulted in a gradual increase in intracellular calcium in neurons (+63%), microglia (+251%), and astrocytes (+52%). Pretreatment of neural cultures with CSF(tox) resulted in an exaggerated calcium response to a brief pulse of glutamate and a > 90% suppression of the rate of recovery of intracellular calcium. Attempts to model the deficit using inhibitors of calcium transport across endoplasmic reticulum, mitochondrial, or plasma membrane indicated that blockade of the plasma membrane sodium/calcium exchanger was best able to reproduce the deficits seen during exposure to CSF(tox). Because the inability of cells to maintain calcium homeostasis would lead to exaggerated responses from a wide variety of stimuli, therapeutics designed to facilitate calcium transport from the cell may provide more comprehensive and effective intervention than strategies targeted to specific receptor pathways.

Highly active antiretroviral therapy improves neurocognitive functioning.

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.

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

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.