CNS-Targeted Antiretroviral Strategies: When Are They Needed and What to Choose
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 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.
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.
KeywordsHIV-associated neurocognitive disorders Cerebrospinal fluid Antiretrovirals Pharmacokinetics Pharmacodynamics Compartmentalization
Compliance with Ethical Standards
Conflict of Interest
Andrea Calcagno received research grants from Gilead, BMS, and Viiv and has received payment for lectures from Abbvie, BMS, Gilead, Janssen-Cilag, MSD, and Viiv.
Stefano Bonora received research grants from Gilead, BMS, and Viiv and has received payment for lectures from Abbvie, BMS, Gilead, Janssen-Cilag, MSD, and Viiv.
Ambra Barco and Mattia Trunfio have no conflict of interest to declare.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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