Dolutegravir/Lamivudine for Maintenance of Virological Suppression in Persons with Historical Suspected or Confirmed Resistance to Lamivudine: Week 48 Results of a Single-Arm, Open-Label, Multicentre, Phase IIA Clinical Trial.
Rosa De Miguel, María de Lagarde Sebastian, José Luis Blanco Arévalo, Adriana Pinto-Martinez, Rocío Montejano, Angela Gutiérrez Liarte, Roser Navarro-Soler, Esperanza Cañas-Ruano, Alexis Inciarte, Luz Martin-Carbonero, Arkaitz Imaz, Cristina Hernández Gutiérrez, Antonio Ocampo, Pedro Gil Divasson, Rafael Delgado, Federico Pulido, Jose R Arribas
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引用次数: 0
Abstract
Background: We investigated the efficacy of dolutegravir/lamivudine for maintenance treatment for people with HIV and previous lamivudine resistance.
Methods: Open-label, single arm, multicentric clinical trial including virologically suppressed PWH with historical lamivudine resistance (confirmed by genotypic testing or suspected based on clinical history), no integrase resistance and CD4+ >200 cells/mm3 whose ART was changed to dolutegravir/lamivudine if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Proviral DNA next-generation sequencing (NGS) was retrospectively performed in baseline samples. Primary endpoint was proportion of participants with HIV-1 RNA viral load (VL) ≥50 copies/mL at 48 weeks in the intention-to-treat-exposed (ITT-e) population using the Food and Drug Administration snapshot algorithm.
Results: 121 participants enrolled, 114 with a prior genotype with M184V/I, mean virological suppression of 9 years. 24 (19·8%) had the M184V/I in baseline proviral DNA NGS (>5% threshold). At 48 weeks, 4 participants had a VL ≥50 copies/mL (3·3%, 95% CI: 0·9%-8·2%, FDA-Snapshot ITT-e): 1 confirmed virologic withdrawal, 1 precautionary virologic withdrawal and 2 discontinued from study treatment for other reasons with last VL ≥ 50 copies/mL; none had M184V/I in baseline proviral DNA NGS and there was no emergent integrase resistance. 90·1% participants (109/121) had a VL<50 copies/mL (95% CI: 83·3%-94·8%) and there were no data for 6·6 % (8/121 participants) at 48 weeks.
Conclusions: After excluding lamivudine mutations in proviral DNA by population sequencing, dolutegravir/lamivudine effectively maintained virological suppression in PWH with CD4+ >200 cells/mm3 and history of lamivudine resistance. Notably, no treatment-emergent resistance was observed.
期刊介绍：
Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.
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