Evolving clinical phenotypes in HIV-associated neurocognitive disorders

This review describes changes in the presentation of HIV Associated Neurocognitive Disorders (HAND) comparing the current combination antiretroviral therapy (cART) treatment era, to the pre-cART era

Serum Neopterin Level Predicts HIV-Related Mortality but Not Progression to Aids or Development of Neurological Disease in Gay Men and Parenteral Drug Users

Objective: To investigate the ability of elevated serum neopterin levels to predict independently mortality, progression to acquired immunodeficiency syndrome, and development of neurological disease. Design: Cross-sectional and longitudinal study of gay and/or bisexual men and parenteral drug users. Setting and Patients: Patients included human immunodeficiency virus (HIV)—negative and —positive gay and/or bisexual men and parenteral drug—using men and women who volunteered for an outpatient study of the natural history of HIV infection. Results: Serum neopterin levels were significantly elevated in HIV-positive patients (mean, 18.0 nmol/L; SD, 19.2 nmol/L), compared with those in HIV-negative patients (mean, 7.5 nmol/L; SD, 5.5 nmol/L) (P<.001). No differences in the serum neopterin levels could be detected between gay men and parenteral drug users. In HIV-positive patients, women had a higher serum neopterin level than did men (P=.03). The elevated serum neopterin levels were associated with an advanced clinical stage of HIV infection. After adjusting for the CD4 lymphocyte count and other potential confounders, the serum neopterin level was a significant independent predictor of mortality. The elevated serum neopterin levels did not predict progression to acquired immunodeficiency syndrome or development of clinically significant neurological disease. Conclusion: An elevated serum neopterin level predicts mortality, but it does not predict progression to acquired immunodeficiency syndrome or development of neurological disease among HIV-infected individuals

Peripheral neuropathy in HIV-infected and uninfected patients in Rakai, Uganda

OBJECTIVE: To determine the prevalence, risk factors, and functional impairment associated with peripheral neuropathy in a prospective cohort of adults in rural Uganda. METHODS: Eight hundred participants (400 HIV- and 400 antiretroviral-naive HIV+) in the Rakai Community Cohort Study underwent detailed neurologic evaluations including assessment of neuropathy symptoms, functional measures (Patient Assessment of Own Functioning Inventory and Karnofsky Performance Status scores), and neurologic evaluation by a trained medical officer. Neuropathy was defined as ≥1 subjective symptom and ≥1 sign of neuropathy on examination. Neuropathy risk factors were assessed using log binomial regression. RESULTS: Fifty-three percent of participants were men, with a mean (SD) age of 35 (8) years. Neuropathy was present in 13% of the cohort and was more common in HIV+ vs HIV- participants (19% vs 7%, p < 0.001). Older age (relative risk [RR] 1.04, 95% confidence interval [CI] 1.02-1.06), female sex (RR 1.49, 95% CI 1.04-2.15), HIV infection (RR 2.82, 95% CI 1.86-4.28), tobacco use (RR 1.59, 95% CI 1.02-2.48), and prior neurotoxic medication use (RR 2.08, 95% CI 1.07-4.05) were significant predictors of neuropathy in the overall cohort. Only older age was associated with neuropathy risk in the HIV+ (RR 1.03, 95% CI 1.01-1.05) and HIV- (RR 1.06, 95% CI 1.02-1.10) cohorts. Neuropathy was associated with impaired functional status on multiple measures across all participant groups. CONCLUSIONS: Peripheral neuropathy is relatively common and associated with impaired functional status among adults in rural Uganda. Older age, female sex, and HIV infection significantly increase the risk of neuropathy. Neuropathy may be an underrecognized but important condition in rural Uganda and warrants further study

Depression symptoms and cognitive function among individuals with advanced HIV infection initiating HAART in Uganda

Background Among patients with HIV infection, depression is the most frequently observed psychiatric disorder. The presence of depressive symptoms and cognitive dysfunction among HIV patients has not been well studied in Sub-Saharan Africa. Initiation of highly active antiretroviral therapy (HAART) may have an effect on the prevalence and the change over time of depression symptoms and cognitive impairment among HIV-positive individuals. Methods We recruited 102 HIV-positive individuals at risk of cognitive impairment who were initiating HAART and 25 HIV-negative individuals matched for age and education. Depression was assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D). Neurocognitive assessment included the International HIV Dementia Scale (IHDS), an 8 test neuropsychological battery and the Memorial Sloan Kettering scale. Assessments were carried out at 0, 3 and 6 months. Results The HIV-positive group had more respondents with CES-D score > 16 than the HIV-negative group at all 3 clinic visits (54%Vs 28%; 36% Vs 13%; and 30% Vs 24% respectively; all p < 0.050 OR 2.86, 95% CI: 1.03, 7.95, p = 0.044). The HIV positive group had higher likelihood for cognitive impairment (OR 8.88, 95% CI 2.64, 29.89, p < 0.001). A significant decrease in the mean scores on the CES-D (p = 0.002) and IHDS (p = 0.001) occurred more in the HIV-positive group when compared to the HIV-negative group. There was no association between clinical Memorial Sloan Kettering score and depression symptoms (p = 0.310) at baseline. Conclusion Depression symptomatology is distinct and common among cognitively impaired HIV patients. Therefore individuals in HIV care should be screened and treated for depression

Cerebral Single-Photon Emission Computed Tomography Abnormalities in Human Immunodeficiency Virus Type 1-Infected Gay Men without Cognitive Impairment

Objective: To determine whether technetium Tc 99m exametazime single-photon computed emission tomography (SPECT) can distinguish gay human immunodeficiency virus (HIV)—positive subjects, both with and without mild cognitive impairment, from gay HIV-negative control subjects. Design: Twenty HIV-positive subjects (12 without cognitive impairment and eight with mild cognitive impairment) and 10 HIV-negative subjects underwent neurological, neuropsychological, magnetic resonance imaging, and technetium Tc 99m exametazime SPECT examinations. Setting: Subjects were recruited from a natural history study of gay men with HIV infection. Patients: Subjects from the cohort who had previously participated in a magnetic resonance imaging study were selected for the SPECT study. Main Outcome Measures: The SPECT scans were rated as abnormal if focal defects, confirmed by a horizontal profile analysis, were seen. Results: Sixty-seven percent of HIV-positive subjects without cognitive impairment, 88% of HIV-positive subjects with mild cognitive impairment, and 20% of HIV-negative subjects had abnormal SPECT scans (P<.05 for both HIV-positive groups when each group was compared with HIV-negative subjects). Conclusion: Compared with gay HIV-negative control subjects, focal SPECT defects are seen with an increased frequency in HIV-positive gay men without cognitive impairment and in HIV-positive gay men with mild cognitive impairment

Neurologic Signs and Symptoms in a Cohort of Homosexual Men Followed for 4.5 Years

We traced the development of neurologic impairment in 207 homosexual men (123 human immunodeficiency virus [HIV]-positive and 84 HIV-negative controls) over 4.5 years of follow-up. We applied generalized estimating equations to logistic regression analyses with repeated measures to examine the differences between HIV-positive and HIV-negative subjects with respect to the likelihood of developing six neurologic outcomes derived from a factor analysis, significant neurologic impairment (modified Kurtzke disability score of ≥3), or significant neuropsycholog-ical impairment. We found that, over time, HIV-positive subjects were more likely to develop clinically significant ex-trapyramidal signs and frontal release signs than HIV-negative subjects. Controlling for age or education, as CD4 count declined, the odds of developing significant extrapyramidal signs, abnormalities in alternating movements, frontal release signs, and a Kurtzke score ≥3 increased. HIV-positive subjects were almost five times as likely (odds ratio [OR], 4.6; 95% CI, 1.6 to 13.4) as HIV-negative subjects to stay the same or worsen neurologically on the next visit, and those with CD4 ≥200 were 4.8 times as likely (OR, 4.8; 95% CI, 2.2 to 10.7) to maintain or worsen neurologically relative to those with higher CD4 counts. We conclude that neurologic impairment becomes increasingly apparent over time in HIV-infected men, especially in those with low CD4 counts

A Comparison of Cerebral Spect Abnormalities in Hiv-Positive Homosexual Men with and without Cognitive Impairment

Objective: To determine whether technetium Tc 99m exametazime (HMPAO) single-photon emission computed tomography (SPECT) can distinguish between human immunodeficiency virus (HIV)-positive homosexual men with normal neuropsychologic test results and HIV-positive homosexual men with abnormal neuropsychologic test results. Design: Neurologic, neuropsychologic, magnetic resonance imaging, and Tc 99m HMPAO SPECT examinations were performed on 10 HIV-positive homosexual men without cognitive impairment and five HIV-positive homosexual men with cognitive impairment. Patients: Human immunodeficiency virus—positive homosexual men from New York City were recruited for the study. Main Outcome Measures: Findings on SPECT scans were evaluated qualitatively for focal defects, heterogeneity of the cortical margin, white matter hypoperfusion, and decreased global cortical uptake. All SPECT focal defects were coregistered with magnetic resonance images; SPECT heterogeneity and global cortical uptake were also measured quantitatively. Results: Coregistration with magnetic resonance imaging revealed that 63% of the focal SPECT defects corresponded to brain gyri and 37% corresponded to sulci. There was no significant difference in the frequency of qualitative or quantitative SPECT abnormalities between HIV-positive homosexual men with and without cognitive impairment. However, after examining individual neuropsychologic test factors, impaired motor speed performance was associated with decreased quantitative global cerebral uptake. Conclusions: Qualitative SPECT abnormalities are not increased in frequency in HIV-positive homosexual men with global cognitive impairment compared with those in HIV-positive homosexual men without cognitive impairment. Impaired motor speed performance may be associated with decreased quantitative global cerebral uptake

Longitudinal neuropsychological test performance among HIV seropositive individuals in Uganda

To evaluate longitudinal neuropsychological testing performance over a 12 month period among HIV+ individuals, and to evaluate the impact of antiretroviral therapy (ART) initiation on neuropsychological test changes in Uganda

Pattern of neuropsychological performance among HIV positive patients in Uganda

BACKGROUND: Few studies have examined cognitive functioning of HIV positive patients in sub-Saharan Africa. It cannot be assumed that HIV positive patients in Africa exhibit the same declines as patients in high-resource settings, since there are differences that may influence cognitive functioning including nutrition, history of concomitant disease, and varying HIV strains, among other possibilities. Part of the difficulty of specifying abnormalities in neuropsychological functioning among African HIV positive patients is that there are no readily available African normative databases. The purpose of the current study was to evaluate the pattern of neuropsychological performance in a sample of HIV positive patients in comparison to HIV negative control subjects in Uganda. METHODS: The neuropsychological test scores of 110 HIV positive patients (WHO Stage 2, n = 21; WHO Stage 3, n = 69; WHO Stage 4, n = 20) were contrasted with those of 100 control subjects on measures of attention/concentration, mental flexibility, learning/memory, and motor functioning. RESULTS: Analysis of covariance (ANCOVA) revealed significant group differences on measures of verbal learning and memory, speed of processing, attention and executive functioning between HIV seropositive and seronegative subjects. CONCLUSION: Ugandan patients with HIV demonstrated relative deficits on measures of verbal learning and memory, speed of processing, attention, and executive functioning compared to HIV negative controls. These results from a resource limited region where clades A and D are prevalent are consistent with previous findings in the developed world where clade B predominates

The neurologic phenotype of South African patients with HIV-associated neurocognitive impairment.

BackgroundThe neurologic manifestations of HIV include a spectrum of HIV-associated neurocognitive disorders, as well as a cluster of neurologic symptoms and signs. The neurologic manifestations have been modified but not eradicated by antiretroviral therapy (ART). We describe the neurologic phenotype in South African patients with predominant HIV-1 subtype C infection on ART and its association with neurocognitive impairment and efavirenz and 8-hydroxy-efavirenz concentrations.MethodsWe conducted a cross-sectional analysis of the neurologic examination findings of HIV+ patients with neurocognitive impairment and used multiple linear regression to explore associations with neurocognitive impairment, efavirenz, and 8-hydroxy-efavirenz pharmacokinetics (plasma and CSF).ResultsWe included 80 participants established on ART (median 40 months) of which 72 (90%) were female. The median age was 35 (interquartile range [IQR], 32-42) and the median Global Deficit Score was 0.94 (IQR 0.63-1.36). We found associations between neurocognitive impairment and neurologic signs: gait (slow walking speed [p = 0.03; R2 = 0.06], gait ataxia [p 2 = 0.21], and abnormal gait appearance [p 2 = 0.18]); coordination (upper limb bradykinesia [p 2 = 0.10] and lower limb bradykinesia [p = 0.01; R2 = 0.10]); reflexes (jaw jerk [p = 0.04; R2 = 0.05] and palmomental response [p = 0.03; R2 = 0.06]); ocular signs (impaired smooth pursuit [p = 0.01; R2 = 0.09] and impaired saccades [p 2 = 0.15]); and motor signs (spasticity [p ≤ 0.01; R2 = 0.15] and muscle weakness [p = 0.01; R2 = 0.08]). No significant associations were found between plasma and CSF efavirenz or 8-hydroxy efavirenz concentrations and any neurologic sign.ConclusionWe found that individual neurologic signs were associated with neurocognitive impairment in South African HIV+ patients with predominant HIV-1 subtype C infection on ART and could be used in clinical practice to assess severity.Registration numberPACTR201310000635418