Overall Tolerability of Integrase Inhibitors in Clinical Practice: Results from a Multicenter Italian Cohort

Arturo Ciccullo, Gianmaria Baldin, Vanni Borghi, Gaetana Sterrantino, Giordano Madeddu, Alessandra Latini, Gabriella d'Ettorre, Alessandro Lanari, Maria Mazzitelli, Manuela Colafigli, Amedeo Ferdinando Capetti, Letizia Oreni, Filippo Lagi, Stefano Rusconi, Simona Di Giambenedetto

Research output: Contribution to journalArticlepeer-review


International guidelines recommend the use of integrase strand transfer inhibitor (INI)-based regimens as first-line antiretroviral (ARV) in both naive and experienced HIV-infected patients. We analyzed a multicenter cohort of HIV-infected patients, both naive and experienced, starting an ARV, including an INI. Chi-square test and nonparametric tests were used to assess differences in categorical and continuous variables, respectively. Kaplan-Meier survival analysis was performed to estimate the probability of maintaining the study drug and Cox-regression analysis to evaluate predictors of discontinuation. We enrolled 4,343 patients: 3,143 (72.4%) were males, with a median age of 49 years (interquartile range 41-55). Naive patients were 733 (16.9%), of whom 168 (22.9%) were AIDS presenters. Overall, 2,282 patients (52.5%) started dolutegravir (DTG), 1,426 (32.8%) raltegravir (RAL), and 635 (14.7%) elvitegravir (EVG). During 10,032 patient years of follow-up (PYFU), we observed 1,278 discontinuations (13 per 100 PYFU); 448 of them (35%) due to simplification and 355 (28%) to toxicities (98 for central nervous system toxicity). Reasons of discontinuation were different between INIs. Estimated probability of maintaining DTG at 3 and 4 years were 81.5% [95% confidence interval (CI): 80.5-82.5] and 76.3% (95% CI: 73.9-78.7), respectively; RAL 61.6% (95% CI: 60.2-63.0) and 54.1% (95% CI: 52.7-55.5); EVG 71.6% (95% CI: 69.2-74.0) and 68.3% (95% CI: 65.3-71.3) (p < .001). At a multivariable analysis, being on a RAL-based ARV [vs. DTG, adjusted hazard ratio (aHR) 2.9, 95% CI: 2.3-3.6, p < .001], a EVG-based ARV (vs. DTG, aHR 1.3 95% CI: 1.1-1.7, p = .049), and a peak HIV-RNA >500k cp/mL (aHR 1.3, 95% CI: 1.1-1.6, p = .006) predicted INI discontinuation. Our data confirm the good tolerability of INIs in clinical practice. Differences emerge between the three drugs in reasons for discontinuation.

Original languageEnglish
Pages (from-to)4-10
Number of pages7
JournalAIDS Res. Hum. Retroviruses
Issue number1
Publication statusPublished - Jan 2021


  • HIV Infections/drug therapy
  • HIV Integrase Inhibitors/adverse effects
  • Heterocyclic Compounds, 3-Ring/adverse effects
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Oxazines/therapeutic use
  • Piperazines/therapeutic use
  • Raltegravir Potassium/adverse effects


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