Drug Design, Development and Therapy (Jun 2022)

Switching from a Non-Protease inhibitor-Based Regimen To the Fixed Dose Combination of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Clinical Practice

  • Ranzenigo M,
  • Gianotti N,
  • Galli L,
  • Poli A,
  • Mastrangelo A,
  • Bruzzesi E,
  • Chiurlo M,
  • Nozza S,
  • Bossolasco S,
  • Spagnuolo V,
  • Mancusi D,
  • Termini R,
  • Carini E,
  • Lazzarin A,
  • Castagna A

Journal volume & issue
Vol. Volume 16
pp. 1975 – 1982

Abstract

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Martina Ranzenigo,1,2 Nicola Gianotti,2 Laura Galli,2 Andrea Poli,2 Andrea Mastrangelo,1,2 Elena Bruzzesi,1,2 Matteo Chiurlo,1,2 Silvia Nozza,2 Simona Bossolasco,2 Vincenzo Spagnuolo,2 Daniela Mancusi,3 Roberta Termini,3 Elisabetta Carini,2 Adriano Lazzarin,2 Antonella Castagna1,2 1Vita-Salute San Raffaele University, Milan, Italy; 2Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; 3Medical Affairs Department, Infectious Disease and Vaccines & PAH, Janssen-Cilag SpA, Cologno Monzese, ItalyCorrespondence: Daniela Mancusi, Medical Affairs Department, Infectious Disease and Vaccines & PAH, Janssen-Cilag SpA, Via Buonarroti 23, Cologno Monzese (MI), 20093, Italy, Tel +0039-345 9581944, Email [email protected]: The primary objective of this study was to estimate the proportion of people living with HIV (PLWH) who switched from a non-protease inhibitor (PI)-based regimen [integrase strand transfer inhibitor (InSTI)-based or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen] to darunavir, cobicistat, emtricitabine, tenofovir alafenamide (D/C/F/TAF).Methods: This was a retrospective study on PLWH treated with a non-PI regimen in January 2017, who switched to D/C/F/TAF or to another antiretroviral therapy (ART) within November 2019. Follow-up was from the start date of D/C/F/TAF until the last available visit or discontinuation for any reason of this regimen. Virological failure (VF) was defined as 2 consecutive HIV-RNA values > 50 copies/mL. Characteristics were reported as median (interquartile range) or frequency (%). A univariate Poisson regression model was used to measure the incidence rate of switch to D/C/F/TAF. Changes in laboratory parameters during D/C/F/TAF were assessed by univariate mixed linear models.Results: Overall, 3076 PLWH were included; 83% were male, median age at ART switch was 50 (42– 56) years and median time on ART was 5.2 (0.3– 13.0) years. PLWH had a median follow-up of 4.76 (3.70– 6.38) years; during 17,099 person-years of follow-up (PYFU), 423/3076 (14%) participants discontinued the non-PI-based regimen and 106/423 (25%) switched to D/C/F/TAF, with an overall incidence rate of switch to D/C/F/TAF of 6.2 per 1000-PYFU (95% CI: 5.0– 7.4). Among PLWH who switched to D/C/F/TAF, the ongoing regimen was based on NNRTIs in 37 (35%) and on InSTIs in 69 (65%). Main reasons leading to switch to D/C/F/TAF included neuropsychiatric adverse events (37%), VF (26%) and Kaposi sarcoma progression (5%).Conclusion: In the last years, a non-negligible proportion of patients on an NNRTI- or an InSTI-based regimen switched to D/C/F/TAF.Keywords: treatment switching, anti-retroviral agents, HIV protease inhibitors, adverse drug events, sustained virologic response

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