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Efavirenz and cognition that matters

Brouillette, Marie-Joséea,b; Fellows, Lesley K.c,d; Mayo, Nancy E.b,e

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doi: 10.1097/QAD.0000000000002545
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We read with interest the publication from the SWEAR study group on the neurocognitive impact of switching away from an efavirenz (EFV)-containing regimen [1]. Cognitive difficulties are prevalent in persons living with HIV and have important consequences for function and quality of life. Any approach that might reduce the negative impact of antiretrovirals on cognition should be welcomed. In this context, the study from the SWEAR group is clinically important.

Central Nervous System (CNS) side effects have been reported with EFV and may be a reason for early discontinuation. For those remaining on EFV and who are impaired on cognitive testing, this study tested whether switching from EFV to rilpivirine would improve cognition. A finding from the SWEAR study was that patients who were switched away from EFV reported less frequent cognitive difficulties after 24 weeks (change of −8.81 on 100) than those continuing with this medication (change of −3.79 on 100). The change in the switch group was likely clinically relevant given the SD at baseline was 11.11 (effect size >0.5 SD, 0.79), whereas the change in the continuation group was less than 0.5 SD with an effect size of 0.26. In contrast to this subjective improvement, there were no important changes observed on a battery of cognitive tests. Broadly similar findings were reported in another recent study on this topic [2].

The authors conclude: ‘… our results show that switching from EFV to rilpivirine was not associated with neurocognitive improvement and suggest that the decision to discontinue tenofovir disoproxil fumarate/emtricitabine/EFV among otherwise healthy individuals should not be driven by the expectation of a cognitive improvement following the switch, because it is unlikely to occur’.

The conclusion echoes the current emphasis on performance-based cognition in the neuro-HIV literature. Self-perceived cognition is either not systematically documented or relegated to a secondary outcome. This is unfortunate given the key importance patients place on self-perceived cognition, but also its established role in explaining function and quality of life. Indeed, in our prospective Canadian study (N = 856) [3], self-perceived cognition was a stronger predictor of work status, work productivity, social function, health perception and quality of life than performance-based cognition [4–6].

The discrepancy between impairment on cognitive testing and self-perceived cognition is well known [7–9]. Both are important sources of information about how the patient is doing. Self-reports may more closely reflect real-world difficulties [7]. Our interpretation of this emerging literature is that switching away for EFV may in fact yield real-world benefits to the patient. Further documentation of the impact of this change on measured and self-perceived cognition, as well as on function and quality of life, is warranted.


Conflicts of interest

There are no conflicts of interest.


1. Lapadula G, Bernasconi DP, Bai F, Foca E, Di Biagio A, Bonora S, et al. Switching from efavirenz to rilpivirine improves sleep quality and self-perceived cognition but has no impact on neurocognitive performances. AIDS 2020; 34:53–61.
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