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