title: Neurotoxicity in the Post-HAART Era: Caution for the Antiretroviral Therapeutics.
abstract: Despite the advent of highly active antiretroviral therapy (HAART), HIV-associated neurological disorders (HAND) remain a major challenge in human immunodeficiency virus (HIV) treatment. The early implementation of HAART in the infected individuals helps suppress the viral replication in the plasma and other compartments. Several studies also report the beneficial effect of drugs that successfully penetrate central nervous system (CNS). However, recent data in both clinical setup and in in vitro studies indicate CNS toxicity of the antiretrovirals (ARVs). Although the evidence is limited, correlation between prolonged use of ARVs and neurotoxicity strongly suggests that it is essential to study the underlying mechanisms responsible for such toxicity. Furthermore, closer attention toward clinical outcomes is required to screen various ARV regimens for their association with HAND and other comorbidities. A growing body of literature also indicates a possible role of accelerated aging in the antiretroviral therapy-associated neurotoxicity. Lastly, owing to high pill burden, multiple drugs in the HIV treatment also invite a possible role of drug-drug interaction via various cytochrome P450 enzymes. The particular emphasis of this review is to highlight the need to identify alternative approaches in reducing the CNS toxicity of the ARV drugs in HIV-infected individuals.
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108, USA. shahank@umkc.edu.
authors.forename: Ankit
authors.initials: A
authors.lastname: Shah
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108, USA.
authors.forename: Mohitkumar R
authors.initials: MR
authors.lastname: Gangwani
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108, USA.
authors.forename: Nitish S
authors.initials: NS
authors.lastname: Chaudhari
authors.affiliation: Department of Pathology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
authors.forename: Alexy
authors.initials: A
authors.lastname: Glazyrin
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108, USA.
authors.forename: Hari K
authors.initials: HK
authors.lastname: Bhat
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO, 64108, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology
keywords: Antiretroviral therapy; Brain; CYP450; HIV; HIV-associated neurocognitive disorder; Neurotoxicity