Executive Dyscontrol of Learning and Memory: Findings from a Clade C HIV-positive South African Sample.

OBJECTIVE: Although pre-clinical work suggests there might be differences in neurovirulence across HIV-1 clades, few studies investigate neuropsychological deficits in the globally predominant clade C infection. The purpose of this study was to investigate verbal learning and memory performance in HIV-positive individuals in Cape Town, South Africa, where clade C is the most prevalent subtype of the virus. METHOD: Using a case-control design, we recruited 53 isiXhosa-speaking, cART-naïve HIV-positive adults and 53 demographically matched HIV-negative controls. Participants were administered a comprehensive neuropsychological test battery. The test of interest was the Hopkins Verbal Learning Test-Revised (HVLT-R); previous studies have used that instrument to identify executive dyscontrol of verbal learning and memory processes in clade B HIV-positive participants. RESULTS: HIV-positive participants showed only partial impairment on the HVLT-R's learning/memory components (e.g., they recalled significantly fewer words across learning trials, but displayed relatively intact performance on delayed recall trials). They also displayed little executive dyscontrol over encoding and retrieval processes (e.g., there were no significant between-group differences on measures of semantic or serial clustering). CONCLUSIONS: Post-cART era studies suggest that verbal learning and memory performance is impaired in clade B samples, at least partially due to executive dyscontrol over encoding and retrieval processes. We found few such impairments in the current clade C sample. These preliminary findings suggest different CNS vulnerability across clades that would have implications for delineating clade-specific neuropathological and neurocognitive clinical features.

Neuropsychological outcomes in adults commencing highly active anti-retroviral treatment in South Africa: a prospective study.

BACKGROUND: Infection with HIV may result in significant neuropsychological impairment, especially in late stage disease. To date, there have been no cohort studies of the impact of highly active anti-retroviral treatment (HAART) in South Africa where clade C HIV is predominant. METHODS: Participants in the current study were recruited from a larger study of HIV-associated neurocognitive disorders (HAND) and included a group of individuals commencing HAART (n = 82). Baseline and one-year neuropsychological function was assessed using a detailed battery, and summary global deficit scores (GDS) obtained. Associations with change in GDS were calculated. RESULTS: Participants had a median CD4 cell count of 166 at baseline and 350 at follow-up. There were significant difference across groups of GDS severity at baseline with respect to level of education and GDS change at one year (p = 0.00 and 0.00 respectively). Participants with severe impairment at baseline improved significantly more than those with lesser degrees of impairment. Significant improvements were observed in the domains of attention, verbal fluency, motor function, and executive functions. There were unadjusted associations between GDS change and male gender, lower levels of education, baseline CD4 count and baseline GDS severity. In an adjusted model, only baseline GDS severity (p = 0.00) remained significant, with a lower level of education nearing significance (p = 0.05). The overall model was highly significant (p = 00; r-squared = 0.58). DISCUSSION: In individuals in late stage HIV commencing HAART in South Africa, those with severe baseline neuropsychological impairment improved significantly more than those less impaired. While improvement across a number of neuropsychological domains was observed, high rates of impairment persisted. CONCLUSIONS: The effects of HAART and participant variables, such as test experience, require clarification. Studies with larger comparison groups, and where HIV disease characteristics are needed to establish whether the trends we identified are clinically meaningful.

Validity of the International HIV Dementia Scale in South Africa.

HIV-associated neurocognitive disorders (HAND) remain prevalent, especially in regions like South Africa where HIV prevalence is high but access to antiretroviral treatment (ART) is limited. The incidence of HIV dementia (HAD) has been halved with the use of ART, but the prevalence remains high. Appropriate brief screening tools to screen for HAD are needed in order to facilitate treatment initiation. The validity of the International HIV Dementia Scale has not been established in a region where infection with HIV clade C is predominant. The International HIV Dementia Scale (IHDS) was administered together with a detailed neuropsychological test battery to 96 HIV-positive individuals who had not received ART and who were attending primary care HIV clinics. The validity of the IHDS was established using a receiver operating characteristic (ROC) analysis. HIV-positive individuals displayed greater impairment when compared to HIV-negative controls on the IHDS and a range of neuropsychological tests. Neuropsychological tests discriminated well across HAND categories for HIV-positive individuals. In ROC analysis, the IHDS showed an area under the curve of 0.64, with a sensitivity of 45% and specificity of 79% at a cutoff score of 10. Individuals with HAD, who screened negative on the IHDS, performed poorly on some tests of executive function. These data suggest that the IHDS may have limitations as a tool to screen for HAD in South Africans infected with HIV. Variable performance in neuropsychological testing may account for false negative screens. The inclusion of brief tests of executive function in a screening battery should be considered.

Characterization of HIV-Associated Neurocognitive Disorders among individuals starting antiretroviral therapy in South Africa.

HIV-Associated Neurocognitive Disorders (HAND) exert an impact on everyday functions, including adherence. The prevalence of and risk factors for HAND in patients commencing anti-retroviral therapy in Southern Africa are unknown. Participants from primary care clinics in Cape Town, South Africa underwent detailed neuropsychological, neuropsychiatric, and neuromedical evaluation. Using the updated American Academy of Neurology (AAN) criteria, participants were classified into categories of HAND, and demographic and clinical risk factors for HIV-dementia (HIV-D) were assessed. The prevalence of mild neurocognitive disorder (MND) and HIV-D were 42.4 and 25.4%, respectively. There were significant associations between lower levels of education and older age with HIV-D, and a trend to association with HIV-D and lower CD4 count. In a regression model, a lower level of education and male gender were predictive of HIV-D. These findings suggest that HAND are highly prevalent in primary care settings in South Africa where clade C HIV is predominant.