Neurological Evaluation of the AIDS Dementia Complex in Actg Clinical Trials

Price, Richard

Abstract

This project will evaluate the effect of antiretroviral therapy of the development and progression of the AIDS dementia complex (ADC) in the context of large-scale, Phase III ACTG clinical trials. The incorporation of neurological data collection in large treatment trials provides the opportunity to evaluate treatment effects with respect to preventions as well as therapy of ADC. The strategy of complementary brief (MICRO) and more extended (MACRO) neurological evaluations is described in the context of ACTG Protocol 193, a 'salvage' protocol designed to assess efficacy of antiretroviral treatment in a very difficult group of HIV-1-infected subjects suffering from late-stage disease with less that 50 CD4+ T-lymphocytes per cu.mm and 6 months of prior nucleoside therapy. ACTG Protocol 193 is a three-arm randomized, double-blind study designed to determine the relative efficacy of two regimens of combination nucleoside antiretroviral therapy and a regimen of monthly alternative nucleoside therapy. The principal endpoint of ACTG 193 is survival. However, the MICRO neurological evaluation is an intrinsic part of the protocol assessment for all subjects, and the MACRO neurological evaluation is one of three specialized substudies associated with this protocol. The overall strategy proposed in this project (combining the MICRO neurological evaluation on all subjects with a subset of subjects at selected AIDS Clinical Trial Units (ACTU's)) will provide a way to obtain modest but functionally significant neurological data obtained from a subset of ACTU's with requisite expertise. This approach has been successfully tested in limited fashion in other ACTG protocols. Thus, this project seeks (1) to assesses treatment efficacy with respect to ADC outcome in major ACTG treatment trials, and (2) to continue to refine neurological assessment methodology for ADC in the context of MICRO and MACRO studies.