Does Efavirenz Replacement Improve Neurological Function in Treated HIV Infection?

B Payne; TJ Chadwick; A Blamire; KN Anderson; J Parikh; J Qian; AM Hynes; J Wilkinson; DA Price


HIV Medicine. 2017;18(9):690-695. 

In This Article

Abstract and Introduction


Objectives The contribution of specific antiretroviral drugs to cognitive function in HIV-infected people remains poorly understood. Efavirenz (EFV) may plausibly cause cognitive impairment. The objective of this study was therefore to determine whether chronic EFV therapy is a modifier of neurocognitive and neurometabolic function in the setting of suppressive highly active antiretroviral therapy.

Methods We performed an open-label phase IV controlled trial. Adult subjects who were stable on suppressive EFV therapy for at least 6 months were switched to ritonavir-boosted lopinavir (LPV/r) with no change in the nucleoside reverse transcriptase inhibitor (NRTI) backbone. The following parameters were assessed before and 10 weeks after therapy switch: cognitive function (by CogState® computerized battery); brain metabolites (by proton magnetic resonance spectroscopy); brain activity [by attentional processing task-based functional magnetic resonance imaging]; and sleep quantity and quality [by sleep diary, Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale].

Results Sixteen subjects completed the study. Despite most subjects (81%) self-reporting memory problems at baseline, cognitive function, brain metabolites, and brain activity showed no change at 10 weeks after switch. Sleep quality improved on switch off EFV [mean PSQI (standard deviation): EFV, 8.5 (6.5); LPV/r, 5.8 (5.5); mean difference −0.4; 95% confidence interval −6.0 to −0.7].

Conclusions This is the first study to assess the effects of chronic EFV therapy on neurological function in a controlled setting. We conclude that EFV withdrawal is unlikely to result in significant modification of neurocognitive function in otherwise stable HIV-infected people.


Mild cognitive impairment remains common in the highly active antiretroviral therapy (HAART) era, but the reasons for this remain incompletely understood.[1] In particular, the role of specific antiretroviral drugs in mediating cognitive function has received relatively little attention.[2] While it is essential to treat viral replication in the central nervous system (CNS), it is plausible that some antiretroviral drugs also have adverse effects on neuronal function. Efavirenz (EFV) remains one of the most commonly used antiretroviral drugs. It is well recognized that CNS side effects (especially sleep disturbance) are common in the first 6 weeks of EFV therapy and sometimes lead to discontinuation, but generally subside with continued therapy.[3,4] Some recent observational studies have suggested that EFV may additionally be associated with increased rates of cognitive impairment, a notion that is supported by some neurotoxicity data from animal and in vitro studies.[5–10] This hypothesis, however, remains controversial and has not been confirmed in a controlled trial.

The aim of this study was therefore to determine whether chronic EFV therapy is a modifier of neurocognitive function in the setting of suppressive HAART.