Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance

Abstract

Objective Determine if antiretroviral (ARV) regimens with good central nervous system (CNS) penetration control HIV in cerebrospinal fluid (CSF) and improve cognition. Design Multi-site longitudinal observational study. Setting Research clinics. Subjects 101 individuals with advanced HIV beginning or changing a new potent ARV regimen. Data for 79 subjects were analyzed. Participants underwent structured history and neurological examination, venipuncture, lumbar puncture, neuropsychological tests at entry, 24 and 52 weeks. Intervention ARV regimens were categorized as CNS penetration effectiveness (CPE) rank ≥ 2 or < 2. Generalized estimating equations were used to examine associations over the course of the study. Main Outcome Measures Concentration of HIV RNA in CSF and blood, neuropsychological test scores. Results Odds of suppression of CSF HIV RNA were higher when CPE rank ≥ 2 compared to < 2. Odds of suppression of plasma HIV RNA were not associated with CPE rank. Among subjects with impaired neuropsychological performance at entry, those prescribed regimens with a CPE rank ≥ 2 or more ARVs had lower NPZ4 over the course of the study. Conclusions ARV regimens with good CNS penetration, as assessed by CPE rank, are more effective in controlling CSF (and presumably CNS) viral replication than regimens with poorer penetration. In this study, ARVs with good CNS penetration were associated with poorer neurocognitive performance. A larger, controlled trial is required before any conclusions regarding the influence of specific ARVs on neurocognitive performance should be made.

Randomized Trial of Central Nervous System–Targeted Antiretrovirals for HIV-Associated Neurocognitive Disorder

“…The CNS penetration effectiveness (CPE) method [5] produces rank estimates of the likelihood that different regimens will reduce CNS HIV. Observational studies have yielded mixed results, some suggesting greater benefits with higher CPE, others not [6]. In a recent review [7], more rigorously designed studies with greater power were more likely to demonstrate benefits, a view supported by expert opinion [8].…”

HIV associated neurocognitive dysfunction and its association with CD4 count in HIV positive patients-a hospital based study

“…Antiretroviral regimens with good CNS penetration such as nevirapine, efavirenz were associated with poorer neurocognitive performance according to Marra et al 31 While Cross S et al observed that cART preserves or improves cognition in HIV infected patients after 1 year, irrespective of the regimen's CPE. 32 In our study average duration on cART was 17.2 months.…”

Clinical Trials in Neurovirology: Successes, Challenges, and Pitfalls

“…A theoretical concern that blunts enthusiasm for intensification strategies is the possibility of medication associated toxicity to the CNS [33]. The idea that some antivirals are neurotoxic, and that high CPE might increase toxicity, remains a consideration in therapeutic development [34].…”