HIV and cocaine interplay in HIV-associated neurocognitive disorders

While antiretrovirals are becoming the gold standard in HIV care and are effective in suppressing viremia, the relative inability of these drugs to penetrate the blood-brain barrier, the latency of HIV in the tissues, and the increased life span of individuals on therapy often lead to complications of HIV in the central nervous system (CNS) termed as HIV-associated neurocognitive disorders (HAND). Among the individuals inflicted with HAND, almost 30 % have a history of substance abuse. Among the commonly abused drugs, cocaine is the most widely used and has emerged as a key contributor to the seroprevalence and progression of HIV infection. Both epidemiological and laboratory-based studies demonstrate that cocaine promotes HIV replication and has multifaceted deleterious effects on the various cells of the CNS resulting in a disrupted blood-brain barrier, enhanced glial activation, and neurotoxicity. Effects of cocaine alone or in combination with HIV proteins lead to augmented neuropathogenesis. This review summarizes current understanding of the diverse effects of cocaine on the various cells of the CNS and how the drug synergizes with HIV and HIV proteins to exacerbate neurotoxicity.