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Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients

A Randomized Controlled Trial

Hakkers, Charlotte S., MD*; Arends, Joop E., MD, PhD*; van den Berk, Guido E., MD, PhD; Ensing, Monique H. M., MSc; Hooijenga, Imke, BSc; Vink, Matthijs, PhD§; van Zandvoort, Martine J. E., PhD; Hoepelman, Andy I. M., MD, PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: January 1, 2019 - Volume 80 - Issue 1 - p e14–e22
doi: 10.1097/QAI.0000000000001876
Clinical Science

Background: Efavirenz is well known for its clinical cognitive side effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing efavirenz.

Setting: A randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes.

Methods: Virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA.

Results: Fourteen control and 34 switch subjects completed the study. There were no differences at baseline. Group analysis demonstrated a significantly better improvement for the switch group on the domains attention (P = 0.041) and speed of information processing (P = 0.014). Normative comparison analyses showed that 5 of the 34 patients who switched (15%) improved on NPA score as compared to the control group. Interestingly, subjective improvement after discontinuing efavirenz made 74% of the switch group chose for a regime without efavirenz after study completion.

Conclusions: Switching from Atripla to Eviplera resulted in objective cognitive improvement on the group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients who would benefit from discontinuing efavirenz.

*Department of Internal Medicine, Section Infectious Diseases, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands;

Department of Infectious Diseases, OLVG Hospital, Amsterdam, the Netherlands;

Department of Neuropsychology, University Medical Center Utrecht (UMCU), Utrecht, the Netherlands; and

§Department of Developmental and Experimental Psychology, Utrecht University, Utrecht, the Netherlands.

Correspondence to: Charlotte Hakkers, MD, Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands (e-mail:

Supported by an unrestricted grant from Gilead.

Abstract accepted for presentation at AIDS 2018; July 24, 2018; Amsterdam, the Netherlands.

The authors have no conflicts of interest to disclose.

C.S.H.: data collection, statistical analysis, and writing manuscript. J.E.A.: study design, statistical analysis, and writing manuscript. G.E.B.: data collection and writing manuscript. M.H.M.E.: data collection and writing manuscript. I.H.: data collection. M.V.: statistical analysis and writing manuscript. M.J.E.Z.: study design, data collection, statistical analysis, and writing manuscript. A.I.M.H.: study design, data collection, and writing manuscript.

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Received June 25, 2018

Accepted September 10, 2018

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