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

Abstract

Objective: To determine whether antiretroviral regimens with good central nervous system (CNS) penetration control HIV in cerebrospinal fluid (CSF) and improve cognition.

Design: Multisite longitudinal observational study.

Setting: Research clinics.

Study participants: One hundred and one individuals with advanced HIV beginning or changing a new potent antiretroviral regimen were enrolled in the study. Data for 79 participants were analyzed. Participants underwent structured history and neurological examination, venipuncture, lumbar puncture, and neuropsychological tests at entry, 24, and 52 weeks.

Intervention: Antiretroviral regimens were categorized as CNS penetration effectiveness (CPE) rank of at least 2 or less than 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 and neuropsychological test scores (NPZ4 and NPZ8).

Results: Odds of suppression of CSF HIV RNA were higher when CPE rank was at least 2 than when it was less than 2. Odds of suppression of plasma HIV RNA were not associated with CPE rank. Among participants with impaired neuropsychological performance at entry, those prescribed regimens with a CPE rank of at least 2 or more antiretrovirals had lower composite NPZ4 scores over the course of the study.

Conclusion: Antiretroviral 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, antiretrovirals with good CNS penetration were associated with poorer neurocognitive performance. A larger controlled trial is required before any conclusions regarding the influence of specific antiretrovirals on neurocognitive performance should be made.

Figure 1. Flow chart of number of subjects seen at each visit.

Twenty-two subjects did not start a cART regimen and thus did not contribute data. “Other” includes 1 subject who was too ill to participate, and 1 who died. Five subjects did not return for the week 24 visit, and the reasons are shown in the Figure. Twelve subjects did not return for the week 52 visit. “Other” includes 2 subjects who were not able to go to the study clinic, 1 who was too ill to participate and 1 who failed their appointments. Three patients underwent study visits at 14, 44 and 48 weeks and then discontinued participation. For simplicity, these three visits are not included in the Figure.