Frontiers in Cellular and Infection Microbiology (Jun 2023)

Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

  • José Ramón Santos,
  • Maria Casadellà,
  • Marc Noguera-Julian,
  • Rafael Micán-Rivera,
  • Pere Domingo,
  • Antonio Antela,
  • Joaquin Portilla,
  • Jesús Sanz,
  • Marta Montero-Alonso,
  • Jordi Navarro,
  • Mar Masiá,
  • Mar Masiá,
  • Nieves Valcarce-Pardeiro,
  • Antonio Ocampo,
  • Laura Pérez-Martínez,
  • Coral García-Vallecillos,
  • María Jesús Vivancos,
  • María Jesús Vivancos,
  • Arkaitz Imaz,
  • José Antonio Iribarren,
  • José Hernández-Quero,
  • Judit Villar-García,
  • Pilar Barrufet,
  • Roger Paredes,
  • Roger Paredes,
  • INSTINCT study group,
  • Mariona Perera,
  • Anna Chamorro,
  • Cristina Miranda,
  • Nástor Sánchez,
  • Anna Garcı́á,
  • Núria Pérez,
  • Juan González Garcı́á,
  • María del Mar Gutiérrez,
  • María Gracia Mateo,
  • Elena Losada,
  • Sergio Reus,
  • Vicente Boix,
  • Diego Torrús,
  • Esperanza Merino,
  • Angela Gutiérrez Liarte,
  • Adrià Curran,
  • Félix Gutiérrez,
  • Anna Mariño Callejo,
  • Alvarez Diaz Hortensia,
  • Antonio Ocampo Hermida,
  • Celia Miralles,
  • Laura Labajo Leal,
  • Guillermo Pousada,
  • José Ramon Blanco,
  • José Antonio Oteo,
  • Ibarra Valvanera,
  • Mercedes Sanz,
  • Luis Metola,
  • Juan Pascua,
  • Daniel Podzamczer,
  • Camila Piatti,
  • Maialen Ibarguren,
  • Laia Arbones,
  • Marta Ruiz,
  • Sara Cervanntes,
  • Helena Pera,
  • Jessica Toro,
  • Nuria Perez-Alvarez,
  • Anna Garcia

DOI
https://doi.org/10.3389/fcimb.2023.1187999
Journal volume & issue
Vol. 13

Abstract

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IntroductionSecond-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients.MethodsReal-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated.ResultsVirological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/μL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles.DiscussionWhereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.

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