Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs): data from a real-life setting

J Antimicrob Chemother. 2019 May 1;74(5):1363-1367. doi: 10.1093/jac/dky566.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Lymphocyte Count / statistics & numerical data
  • Cobicistat / adverse effects
  • Cobicistat / therapeutic use
  • Cohort Studies
  • Female
  • HIV Infections / drug therapy*
  • HIV Integrase Inhibitors / adverse effects
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV Seropositivity / drug therapy*
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones / adverse effects
  • Quinolones / therapeutic use
  • Raltegravir Potassium / adverse effects
  • Raltegravir Potassium / therapeutic use
  • Regression Analysis
  • Survival Analysis
  • Treatment Failure

Substances

  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones
  • Raltegravir Potassium
  • elvitegravir
  • dolutegravir
  • Cobicistat