Central nervous system (CNS) infection and the resulting cognitive deterioration have been associated with increased morbidity and mortality in HIV-infected patients in addition to usual markers of disease stage and treatment efficacy, such as CD4+ counts and HIV plasma viral load. Thus, amelioration of neurological symptoms and prevention of clinical disease, is a significant goal of systemic and neurologically-targeted therapy. Despite these considerations, development of systematic neurological evaluation methods in clinical studies and routine care has seriously lagged behind development of immunologic and virologic measures. The primary objective of this project is to develop neuropsychological (NP) testing strategies for monitoring and evaluation of patients with symptomatic and asymptomatic HIV infection. NP testing is the simplest, least invasive neurological assessment instrument and may thus be the only feasible continuous evaluation method, particularly in early stages of the disease. NP batteries will form the core of the proposed neurological evaluation strategies. They will be constructed after extensive review of data collected by the AIDS Clinical Trials Group (ACTG) and the Multicenter AIDS Cohort Study (MACS). An individual NP test will be included in a battery based on the strength of its association with patient survival and laboratory measures versus the complexity of its administration. Thus, multiple testing batteries are likely to be proposed depending on the size and features of the target population and the characteristics of the clinical study. If multiple batteries are proposed, context-dependent guidelines for choosing the most appropriate one will be provided. A secondary aim pertains to derivation of norms for each testing battery, adjusted for demographic and socioeconomic factors (e.g., age, gender, education and race). Related to this objective is the development of guidelines for patient screening that can serve as entry criteria in AIDS Dementia Complex (ADC) studies, as well as performance thresholds that can be used as standards for therapy initiation and modification.