Efavirenz (EFV) association with neurocognitive (NC) impairment is debated. Whether switching away from EFV improves NC 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 NC assessment (Z-transformed score below −1 in ≥1 cognitive domains), depression, anxiety or low sleep-quality, were randomized 1:1 to immediate or delayed (24-weeks) switch to TDF/FTC/rilpivirine (RPV). Treatment efficacy, NC function, symptoms and quality of life were evaluated 12, 24 and 48 weeks after randomization.
74 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 ≥1 NC or 2 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 NC 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 arms 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 ≥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.
aSC Malattie Infettive, Ospedale San Gerardo, Monza, Italy;
bUniversity of Milano-Bicocca, Milan, Italy;
cOspedale San Paolo, University of Milan, Milan, Italy;
dClinica di Malattie Infettive e Tropicali, ASST Spedali Civili, University of Brescia, Brescia, Italy;
eClinica di Malattie Infettive, Ospedale San Martino, Genoa, Italy;
fClinica di Malattie Infettive, University of Turin, Turin, Italy;
gClinica di Malattie Infettive, IRCCS Fondazione Ca’ Granda Policinico di Milano, University of Milan, Milan, Italy.
Correspondence to Giuseppe Lapadula, M.D., Ph.D., San Gerardo Hospital, Monza, MB Italy. Tel: +email@example.com
Received 19 May, 2019
Revised 4 August, 2019
Accepted 10 August, 2019