title: Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.
abstract: BACKGROUND
  Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited.
  
  
  OBJECTIVE
  We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study.
  
  
  METHODS
  This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen.
  
  
  RESULTS
  Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years.
  
  
  CONCLUSIONS
  In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.
authors.affiliation: 1 Department of Internal Medicine, Hospital Dos Capuchos , Lisboa, Portugal.
authors.forename: Eugénio
authors.initials: E
authors.lastname: Teófilo
authors.forename: Nuno
authors.initials: N
authors.lastname: Rocha-Pereira
authors.forename: Birger
authors.initials: B
authors.lastname: Kuhlmann
authors.forename: Antonio
authors.initials: A
authors.lastname: Antela
authors.forename: Heribert
authors.initials: H
authors.lastname: Knechten
authors.forename: Jesús
authors.initials: J
authors.lastname: Santos
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Jiménez-Expósito
mesh_terms: D000293:Adolescent; D000328:Adult; D000069446:Atazanavir Sulfate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D015497:HIV-1; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000069446:Atazanavir Sulfate; D019438:Ritonavir
keywords: HIV-1; antiretroviral therapy; estimated glomerular filtration rate; hyperbilirubinemia; observational study; persistence; resistance; ritonavir-boosted atazanavir