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The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.

HIV-1 infection can be associated with neuropsychological (NP) deficits ranging from subtle to severe. The purpose of this study was to evaluate the functional, or "real-world" impact of HIV-associated NP impairment in a group of 267 HIV-infected participants. All participants received comprehensive NP, neuromedical, and standardized functional evaluations that included laboratory measures of shopping, cooking, financial management, medication management and vocational abilities. Compared to NP-normal participants, those with NP impairment performed significantly worse on all laboratory measures of everyday functioning. Multivariate analyses revealed that the NP ability domains of Abstraction0Executive Function, Learning, Attention0Working Memory and Verbal abilities most strongly and consistently predicted failures on the functional battery. Both NP impairment and impairment on the functional battery were significantly associated with subjective experiences of cognitive difficulties, as well as unemployment and increased dependence in activities of daily living; multivariate prediction models that also considered depressed mood and biological measures of disease progression revealed that impairment on the functional battery and depression were the only unique predictors of all three indicators of "real-world" functioning. The current results add to growing evidence concerning the clinical significance of HIV-associated NP impairment. Objective, laboratory based functional measures, such as those used here, may compliment NP testing in future studies directed at understanding the impact on life quality of central nervous system disorders and their treatments. Finally, there is a need for additional research investigating the apparently independent effect of depression on level of everyday functioning in HIV infected persons. (JINS, 2004, 10, 317-331.)

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