title: Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility.
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.
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy. massimiliano.fabbiani@gmail.com.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fabbiani
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Grima
authors.forename: Benedetta
authors.initials: B
authors.lastname: Milanini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mondi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Baldonero
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ciccarelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.forename: Maria C
authors.initials: MC
authors.lastname: Silveri
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001692:Biological Transport; D018791:CD4 Lymphocyte Count; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D003430:Cross-Sectional Studies; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016017:Odds Ratio; D010539:Permeability; D012107:Research Design; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents