HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors.

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.

Motor function and human immunodeficiency virus-associated cognitive impairment in a highly active antiretroviral therapy-era cohort.

BACKGROUND: Cognitive impairment has long been recognized as a manifestation of human immunodeficiency virus (HIV) infection. However, highly active antiretroviral therapy (HAART) has altered the neurologic manifestations of HIV. OBJECTIVES: To develop a measure to quantify the motor abnormalities included in the original descriptions of HIV-associated dementia (HAD); to determine whether motor, affective, and behavioral dysfunction predict cognitive impairment; and to determine whether quantitative motor testing is a helpful adjunct in the diagnosis of HAD in a complex population from the HAART era. DESIGN: Neurologic and neuropsychological data were collected from the Manhattan HIV Brain Bank, a longitudinal cohort study of patients with advanced HIV. The HIV-Dementia Motor Scale (HDMS) was developed and validated and cognitive and affective or behavioral function was quantified using global neuropsychological T scores, the Beck Depression Inventory (BDI), and an independent assessment of apathy. Relationships among cognitive, motor, affective, and behavioral performance were examined using correlation, linear regression, and analyses of variance. SETTING: An urban AIDS research center. PARTICIPANTS: A total of 260 HIV-positive, predominantly minority patients. MAIN OUTCOME MEASURES: The HDMS scores and global neuropsychological T scores. RESULTS: The HDMS and BDI scores were independent predictors of cognitive impairment. Significant cognitive impairment was found in patients with motor dysfunction. Patients diagnosed as having HAD had a greater degree of motor impairment than those with other neurocognitive diagnoses. CONCLUSIONS: Motor, affective, and behavioral abnormalities predict cognitive impairment in HIV-positive patients in this HAART-era cohort. The HDMS may be useful in the assignment of HIV-associated neurocognitive impairment in HIV populations in which normative data or neuropsychological test design is not optimal.