Antiretroviral Neuropenetration Scores Better Correlate with Cognitive Performance of HIV-Infected Patients after Accounting for drug Susceptibility. Issue 4 (May 2015)

• Record Type: Journal Article
• Authors: Fabbiani, Massimiliano; Grima, Pierfrancesco; Milanini, Benedetta; Mondi, Annalisa; Baldonero, Eleonora; Ciccarelli, Nicoletta; Cauda, Roberto; Silveri, Maria C; De Luca, Andrea; Giambenedetto, Simona Di
• Is Part Of: Antiviral therapy. Volume 20:Issue 4(2015)
• Page Start: 441
• Page End: 447
• Publication Date: 2015-05
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP2926
• Languages: English
• ISSNs: 1359-6535

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.