CNS-Targeted Antiretroviral Strategies: When Are They Needed and What to Choose

• Published in: Current HIV/AIDS reports Vol. 15; no. 1; pp. 84 - 91
• Main Authors: Calcagno, Andrea, Barco, Ambra, Trunfio, Mattia, Bonora, Stefano
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2018; Springer Nature B.V
• Subjects: AIDS Dementia Complex - drug therapy; AIDS Dementia Complex - pathology; Anti-HIV Agents - cerebrospinal fluid; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Antiviral agents; Benzoxazines - cerebrospinal fluid; Benzoxazines - therapeutic use; Brain - virology; CD4 antigen; Central nervous system; Central Nervous System - virology; Central Nervous System and Cognition (SS Spudich; Cerebrospinal fluid; Cerebrospinal Fluid - virology; Clinical trials; Cognition; Drug resistance; HIV; HIV Infections - drug therapy; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Immune response; Immunosuppressive agents; Macrophages; Medicine; Medicine & Public Health; Neopterin - cerebrospinal fluid; Neopterin - therapeutic use; Nervous system; Neurocognitive Disorders - drug therapy; Neurocognitive Disorders - pathology; Neurocognitive Disorders - virology; Neurotoxicity; Ribonucleic acid; Risk factors; RNA; Section Editor; Substantia alba; Topical Collection on Central Nervous System and Cognition; Compartmentalization; Antiretrovirals; Pharmacodynamics; Cerebrospinal fluid; Pharmacokinetics; HIV-associated neurocognitive disorders
• ISSN: 1548-3568; 1548-3576; 1548-3576
• DOI: 10.1007/s11904-018-0375-2

Purpose of Review Neurocognitive disorders are not uncommon in HIV-positive patients but their pathogenesis is multifactorial and incompletely understood. After excluding contributing comorbidities, several factors may impair neurocognition including severe immune suppression, incomplete antiviral efficacy, drugs' persistent immune activation, vascular abnormalities, and drugs' neurotoxicity. The effectiveness of targeted antiretroviral strategies on these risk factors is unknown. Recent Findings Recent studies support the idea that residual cerebrospinal fluid HIV RNA in the setting of plasma viral suppression is associated with compartmental immune activation but the link to neuronal damage is debated. Some authors have reported an incomplete antiviral efficacy in macrophage-derived cells but targeted antiretroviral regimen switches have not been performed. Additionally, improvements in neurocognition using drugs with better central nervous system penetration or maraviroc (associated with favorable immunological properties) have been observed in pilot studies. Trials evaluating specific interventions for cardiovascular health (including brain white matter abnormalities) and neurotoxicity of antiretrovirals are warranted. Summary Central nervous system-targeted antiretroviral strategies are needed in patients with uncontrolled cerebrospinal HIV replication, and they may be suggested in subjects with low CD4 nadir, individuals carrying drug-resistant viruses, and those with compartmental immune activation.