Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility

Antivir Ther. 2015;20(4):441-7. doi: 10.3851/IMP2926. Epub 2014 Dec 17.

Abstract

Background: The aim of the study was to explore how viral resistance and antiretroviral central nervous system (CNS) penetration could impact on cognitive performance of HIV-infected patients.

Methods: We performed a multicentre cross-sectional study enrolling HIV-infected patients undergoing neuropsychological testing, with a previous genotypic resistance test on plasma samples. CNS penetration-effectiveness (CPE) scores and genotypic susceptibility scores (GSS) were calculated for each regimen. A composite score (CPE-GSS) was then constructed. Factors associated with cognitive impairment were investigated by logistic regression analysis.

Results: A total of 215 patients were included. Mean CPE was 7.1 (95% CI 6.9, 7.3) with 206 (95.8%) patients showing a CPE≥6. GSS correction decreased the CPE value in 21.4% (mean 6.5, 95% CI 6.3, 6.7), 26.5% (mean 6.4, 95% CI 6.1, 6.6) and 24.2% (mean 6.4, 95% CI 6.2, 6.6) of subjects using ANRS, HIVDB and REGA rules, respectively. Overall, 66 (30.7%) patients were considered cognitively impaired. No significant association could be demonstrated between CPE and cognitive impairment. However, higher GSS-CPE was associated with a lower risk of cognitive impairment (CPE-GSSANRS odds ratio 0.75, P=0.022; CPE-GSSHIVDB odds ratio 0.77, P=0.038; CPE-GSSREGA odds ratio 0.78, P=0.038). Overall, a cutoff of CPE-GSS≥5 seemed the most discriminatory according to each different interpretation system.

Conclusions: GSS-corrected CPE score showed a better correlation with neurocognitive performance than the standard CPE score. These results suggest that antiretroviral drug susceptibility, besides drug CNS penetration, can play a role in the control of HIV-associated neurocognitive disorders.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Biological Transport
  • CD4 Lymphocyte Count
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Central Nervous System / virology
  • Cognition / drug effects
  • Cognition Disorders / genetics
  • Cognition Disorders / pathology
  • Cognition Disorders / prevention & control*
  • Cognition Disorders / virology
  • Cross-Sectional Studies
  • Disease Susceptibility
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Odds Ratio
  • Permeability
  • Research Design
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents