title: Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study.
abstract: BACKGROUND
  Drug-related toxicity has been one of the main causes of antiretroviral treatment discontinuation. However, its determinants are not fully understood. Aim of this study was to investigate predictors of first-line antiretroviral therapy discontinuation due to adverse events and their evolution in recent years.
  
  
  METHODS
  Patients starting first-line antiretroviral therapy were retrospectively selected. Primary end-point was the time to discontinuation of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and multivariable Cox regression models upon clinical/demographic/chemical baseline patients' markers.
  
  
  RESULTS
  1,096 patients were included: 302 discontinuations for adverse events were observed over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism, lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated with an increased hazard of adverse events were: older age, CDC stage C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz (actually recommended for first-line regimens) were associated to an increased hazard of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher risk of adverse events.
  
  
  CONCLUSIONS
  After starting antiretroviral therapy, the probability of remaining free from adverse events seems to decrease over time. Among drugs associated with increased toxicity, only one is currently recommended for first-line regimens but with improved drug formulation. Older age, CDC stage, MSM risk factor and gender are also associated with an increased hazard of toxicity and should be considered when designing a first-line regimen.
authors.affiliation: Viral Immunodeficiency Unit, National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy. mauro.zaccarelli@gmail.com
authors.forename: Mattia C F
authors.initials: MC
authors.lastname: Prosperi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fabbiani
authors.forename: Iuri
authors.initials: I
authors.lastname: Fanti
authors.forename: Mauro
authors.initials: M
authors.lastname: Zaccarelli
authors.forename: Manuela
authors.initials: M
authors.lastname: Colafigli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mondi
authors.forename: Alessandro
authors.initials: A
authors.lastname: D'Avino
authors.forename: Alberto
authors.initials: A
authors.lastname: Borghetti
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods*; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011247:Pregnancy; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D028761:Withholding Treatment
chemical_list: D044966:Anti-Retroviral Agents