Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs)

Data from a real-life setting

Antonella D.Arminio Monforte, Alessandro Cozzi-Lepri, Antonio Di Biagio, Giulia Marchetti, Sergio Lo Caputo, Stefano Rusconi, Nicola Gianotti, Valentina Mazzotta, Giovanni Mazzarello, Andrea Costantini, Antonella Castagna, Andrea Antinori

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objectives: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals. Methods: The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression. Results: Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00-3.76, P = 0.05). Conclusions: In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure.

Original languageEnglish
Pages (from-to)1363-1367
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume74
Issue number5
DOIs
Publication statusPublished - Jan 1 2019

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Integrases
Treatment Failure
HIV
dolutegravir
CD4 Lymphocyte Count
Survival Analysis
JTK 303
Cobicistat
Raltegravir Potassium
RNA

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs) : Data from a real-life setting. / Monforte, Antonella D.Arminio; Cozzi-Lepri, Alessandro; Di Biagio, Antonio; Marchetti, Giulia; Lo Caputo, Sergio; Rusconi, Stefano; Gianotti, Nicola; Mazzotta, Valentina; Mazzarello, Giovanni; Costantini, Andrea; Castagna, Antonella; Antinori, Andrea.

In: Journal of Antimicrobial Chemotherapy, Vol. 74, No. 5, 01.01.2019, p. 1363-1367.

Research output: Contribution to journalArticle

Monforte, Antonella D.Arminio ; Cozzi-Lepri, Alessandro ; Di Biagio, Antonio ; Marchetti, Giulia ; Lo Caputo, Sergio ; Rusconi, Stefano ; Gianotti, Nicola ; Mazzotta, Valentina ; Mazzarello, Giovanni ; Costantini, Andrea ; Castagna, Antonella ; Antinori, Andrea. / Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs) : Data from a real-life setting. In: Journal of Antimicrobial Chemotherapy. 2019 ; Vol. 74, No. 5. pp. 1363-1367.
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abstract = "Objectives: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals. Methods: The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression. Results: Two thousand and sixteen patients were included: 310 (15.4{\%}) started raltegravir-based regimens, 994 (49.3{\%}) started dolutegravir-based regimens and 712 (35.3{\%}) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5{\%} for raltegravir, 5.4{\%} for dolutegravir and 6.7{\%} for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4{\%}) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95{\%} CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95{\%} CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95{\%} CI = 1.00-3.76, P = 0.05). Conclusions: In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure.",
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T1 - Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs)

T2 - Data from a real-life setting

AU - Monforte, Antonella D.Arminio

AU - Cozzi-Lepri, Alessandro

AU - Di Biagio, Antonio

AU - Marchetti, Giulia

AU - Lo Caputo, Sergio

AU - Rusconi, Stefano

AU - Gianotti, Nicola

AU - Mazzotta, Valentina

AU - Mazzarello, Giovanni

AU - Costantini, Andrea

AU - Castagna, Antonella

AU - Antinori, Andrea

PY - 2019/1/1

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N2 - Objectives: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals. Methods: The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression. Results: Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00-3.76, P = 0.05). Conclusions: In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure.

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