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

Abstract

BackgroundInfection 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.MethodsParticipants 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.ResultsParticipants 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).DiscussionIn 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.ConclusionsThe 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.

The effects of antiretroviral treatment initiation on cognition in HIV-infected individuals with advanced disease in Pune, India

“…Despite generally positive findings regarding the cognitive benefits of ART initiation, such findings are not universal and not all patients improve with treatment (Cysique et al 2009; Al-Khindi et al 2011; Joska et al 2012). Indeed, some patients show neuropsychological decline while on apparently effective treatment (Robertson et al 2007; Cysique et al 2006).…”

“…A recent study in South Africa found significant improvement in individuals with late stage HIV disease after commencing HAART. However, while improvement across a number of NP domains was observed, high rates of impairment persisted (Joska et al 2012). In this vein, concerns have been raised about the possible neurotoxicity of ARV treatments (Robertson et al 2012).…”

“…For this project lumbar punctures were not feasible, and thus we cannot comment on whether participants achieved CNS viral suppression in addition to suppression in the periphery. In addition, the study only examined one year of follow-up, and it is possible that the cognitive benefits, or potential neurotoxicity-associated changes, may only emerge over longer time periods (Joska et al 2012). Future studies should include cognitive evaluations among individuals who have achieved sustained viral suppression.…”

HIV-associated neurocognitive disorders: Antiretroviral regimen, central nervous system penetration effectiveness, and cognitive outcomes

“…This approach was developed by Joska et al, [28] and the three groups were shown to correlate moderately well with the HAND diagnoses as defined by Antinori et al [1] of normal function, asymptomatic neurocognitive impairment/mild neurocognitive disorder (as these essentially have the same degree of neuropsychological impairment, but differ on functional status) and HIV-D. Using this approach instead of the defined HAND categories removes the need to undertake an assessment of activities of daily living and related functional impairment.…”

Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease

“…Additional research utilizing a larger independent sample in India revealed nearly identical results (Gupta et al 2007). Further, recent work from South Africa where clade C is dominant suggests HIV-associated dementia (HAD) rates exceed 30% among untreated individuals (Joska et al 2011), and significant cognitive deficits across cognitive domains mirror the pattern of impairments common in clade B virus (Joska et al 2012). Neuroimaging studies of HIV-infected adolescents and adults in South Africa (Heaps et al 2012) also reveal abnormalities in the cortical gray and subcortical brain regions, suggesting that despite the reported presence of the Tat C31S substitution, individuals infected with clade C HIV exhibit significant brain abnormalities.…”