HIV Preclinical-Clinical Therapeutics Research: central nervous system approaches

The prevalence of HIV-associated brain disorders is reportedly increasing due, in part, to the prolonged life span of individuals who are surviving well on highly active antiretroviral treatments (HAART). While clinicians report CNS-related deficits that are more subtle in presentation than the frank dementia evident in the pre-HAART era, the milder presentation continues to substantively reduce an individual's quality of life. The development of novel drugs or therapeutic strategies for treating HIV-related CNS disease is important as most investigators agree that the brain is a sanctuary for latent virus, local viral recrudescence, and associated brain inflammatory responses. The prolonged chronic and cumulative effects on the brain of living with HIV-related inflammatory processes, antiretroviral treatments, and their long-term side effects, toxicities, and brain-related aging processes collectively indicate that the burden of CNS and PNS complications will increase profoundly during the upcoming years. Considering the high expense for new drugs entering CNS-related clinical trials and their ultimately low success rate, the NIMH convened a meeting entitled, HIV Preclinical-Clinical Therapeutics Research Meeting, to discuss the current and proposed novel approaches for neuroAIDS drug development and clinical practices. The purposes of the meeting were twofold: to identify the most promising approaches for future neuroAIDS therapeutics development research and to discuss optimal structures and partnerships with industry that may facilitate the successful movement of compounds from the bench to the bedside. Several themes can be derived from the sessions and are highlighted below for preclinical, translational and clinical neuroAIDS therapeutics research.