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00925njm 22002777a 4500 dc De Miguel, Rosa author Rial-Crestelo, David author Domínguez-Domínguez, Lourdes author Montejano, Rocío author Esteban-Cantos, Andres author Aranguren-Rivas, Paula author Stella-Ascariz, Natalia author Bisbal, Otilia author Bermejo-Plaza, Laura author Garcia-Alvarez, Monica author Alejos, Belén author Hernando, Asunción author Santacreu-Guerrero, Mireia author Cadiñanos, Julen author Mayoral, Mario author Castro, Juan Miguel author Moreno, Victoria author Martin-Carbonero, Luz author Delgado, Rafael author Rubio, Rafael author Pulido, Federico author Arribas, José Ramón author ART-PRO, PI16/00837-PI16/00678 study group author 2020-05 Background: We investigated the efficacy of a switch to dolutegravir plus lamivudine in aviremic individuals without evidence of persistent lamivudine resistance-associated mutations in baseline proviral DNA population sequencing. Methods: Open-label, single-arm, 48-week pilot trial. HIV-1 infected adults, naïve to integrase inhibitors, with CD4+ above 350 cell/μL and fewer than 50 HIV-1 RNA copies per mL the year prior to study entry switched to dolutegravir plus lamivudine. Participants were excluded if baseline proviral DNA population genotyping detected lamivudine resistance-associated mutations. To detect resistance minority variants, proviral DNA next-generation sequencing was retrospectively performed from baseline samples. Primary efficacy endpoint was proportion of participants with fewer than 50 HIV-1 RNA copies per mL at week 48. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations. ART-PRO is registered with ClinicalTrials.gov, NCT03539224. Findings: 41 participants switched to dolutegravir plus lamivudine, 21 with lamivudine resistance mutations in historical plasma genotypes. Baseline next-generation sequencing detected lamivudine resistance mutations (M184V/I and/or K65R/E/N) over a 5% threshold in 15/21 (71·4%) and 3/20 (15%) of participants with and without history of lamivudine resistance, respectively. At week 48, 92·7% of participants (38/41) had fewer than 50 HIV-1 RNA copies per mL. There were no cases of virologic failure. Three participants with historical lamivudine resistance were prematurely discontinued from the study (2 protocol violations, one adverse event). Ten participants (4 in the group with historical lamivudine resistance) had a transient viral rebound, all resuppressed on dolutegravir plus lamivudine. There were 28 drug-related adverse events, only one leading to discontinuation. Interpretation: In this pilot trial, dolutegravir plus lamivudine was effective in maintaining virologic control despite past historical lamivudine resistance and presence of archived lamivudine resistance-associated mutations detected by next generation sequencing. Further studies are needed to confirm our results. EBioMedicine . 2020 May;55:102779. 10.1016/j.ebiom.2020.102779 2352-3964 EBioMedicine 32408111 http://hdl.handle.net/20.500.12105/10862 Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO).