Randomized Trial Evaluating the Neurotoxicity of Dolutegravir/Abacavir/Lamivudine and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: GESIDA 9016

Autor: Ignacio Pérez Valero, Juan González García, Pablo Ryan, Joanna Cano, María J Vivancos, Alicia Gonzalez, María Yllescas, Ignacio Santos, Guadalupe Rua, Alfonso Cabello, Guillermo Cuevas, Sara de la Fuente-Moral, Alberto Diaz de Santiago, Miguel Górgolas
Rok vydání: 2020
Předmět:
Zdroj: Open Forum Infectious Diseases
ISSN: 2328-8957
Popis: Background Despite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial. Methods We conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up. Results Thirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF. Conclusions Neuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF.
This clinical trial demonstrates the reversibility of DTG/ABC/3TC-related neuropsychiatric adverse events after switching to another integrase inhibitor-based therapy in virologically suppressed HIV-infected individuals. These results have implications for our understanding of the neurotoxicity profile of dolutegravir and other integrase inhibitors.
Databáze: OpenAIRE
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