Summary

This letter to the editor comments on the SWEAR study that investigated whether switching HIV+ patients from the drug efavirenz (EFV) to rilpivirine(RPV) would improve their neurocognitive function. EFV has been associated with side effects affecting the brain, but it is unclear if switching medications would have a positive impact. The study found that while switching to RPV did not improve objective measures of neurocognitive function, it did lead to fewer cognitive problems experienced by patients in daily life. The authors of the SWEAR study concluded:‘. . .our results show that switching from EFV to rilpivirine was not associated with neurocognitive improvement and suggest that the decision to discontinue(…)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. In this letter to the editor, the authors make the point that self-reported cognitive difficulties do not receive the attention that they deserve. In their prospective Canadian study, self-perceived cognition was a stronger predictor of work status, work productivity, social function, and quality of life than performance-based cognition. Their interpretation of the SWEAR study is that switching away for EFV may, in fact yield real-world benefits to the patient that 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.

Abstract

Background:

Efavirenz (EFV) association with neurocognitive impairment is debated. Whether switching away from EFV improves neurocognitive performances is still controversial.

Methods:

In a randomized open-label controlled trial, patients under effective treatment with tenofovir disoproxil-fumarate (TDF), emtricitabine (FTC) and EFV, who had altered neurocognitive assessment (z-transformed score below −1 in at least one cognitive domain), depression, anxiety or low sleep-quality, were randomized 1 : 1 to immediate or delayed (24-weeks) switch to TDF/FTC/rilpivirine (RPV). Treatment efficacy, neurocognitive function, symptoms and quality of life were evaluated 12, 24 and 48 weeks after randomization.

Findings:

Seventy-four patients were randomized to immediate (36 patients) or delayed switch (38 patients). At baseline, 63 and 25% of patients had z-scores below −1 in at least one or two neurocognitive domains, 31.1, 17.6 and 44.6% had significant depression or anxiety symptoms or low sleep quality. At week 24 (primary end-point), overall neurocognitive improvement was observed, with no statistically significant differences between arms, neither considering the global z score (between arms difference +0.1; P = 0.458), nor domain-specific z scores. Patients switching away from EFV had significant greater improvement of sleep quality index (between-arm difference −1.5; P = 0.011), self-reported cognitive failures (−6.2; P = 0.001) and CNS symptoms score (−5; P = 0.002), but not of anxiety or depression. No protocol defined virological failure, grade at least 3 lab abnormalities or drug-related serious adverse events were reported.

Conclusion:

Our results do not support the hypothesis that switching to RPV improves cognitive function in patient under stable treatment with EFV. Nonetheless, improvements in neuropsychiatric symptoms, sleep quality and self-perceived cognition were observed.

DOI: https://doi.org/10.1097/qad.0000000000002377

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