title: Efficacy, safety and pharmacokinetics of atazanavir (200mg twice daily) plus raltegravir (400mg twice daily) dual regimen in the clinical setting.
abstract: Unboosted atazanavir with raltegravir has been investigated at 300mg twice daily showing frequent hyperbilirubinemia and selection of resistance-associated mutations.
  
  
  
  Atazanavir 200mg twice daily could increase tolerability and plasma exposure.
  
  
  
  Patients on atazanavir/raltegravir (200/400 twice daily), with self-reported adherence >95% and no concomitant interacting drugs were retrospectively evaluated.
  
  
  
  102 patients [72.5% male, age 46.4 years (42-54), BMI 24kg/m2(22-26)] were included. CD4+ T lymphocytes were 417 cell/μL (302-704) and 76 patients (74.5%) had HIV-RNA <50 copies/ml. After 123 weeks 18.6% patients showed virological failure and 3.9% discontinued for intolerance. Available genotypes showed selection of major integrase (7/10 patients) and protease resistance-associated mutations (5/13 patients). In patients switching with dyslipidemia (n=67) total, LDL cholesterol and triglycerides significantly decreased. Patients switching with eCRCL<60ml/min (n=27) had no significant changes while patients with eCRCL >60ml/min showed significant decrease (-9.8ml/min, p=0.003) at 96-weeks. Atazanavir and raltegravir trough concentrations were 321ng/mL (147-720) and 412ng/mL (225-695). Self-reported non-adherence (n=4) was significantly associated with virological failure (p=0.02); patients with virological success had borderline longer previous virological control (33 vs. 18 months, p=0.07).
  
  
  
  Switch to atazanavir/raltegravir was safe and well tolerated allowing optimal drugs' plasma exposure. However, a concerning rate (18.6%) failed with newly selected mutations and stopped ATV/RAL because of DDI and intolerance issues or were lost to follow-up. This regimen might be considered in selected patients, without history of protease inhibitors failure or HBV infection, showing optimal adherence and prolonged suppression.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: letizia.marinaro@gmail.com.
authors.forename: Letizia
authors.initials: L
authors.lastname: Marinaro
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: andrea.calcagno@unito.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calcagno
authors.affiliation: Infectious Diseases Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. Electronic address: diego.ripamonti@hotmail.com.
authors.forename: Diego
authors.initials: D
authors.lastname: Ripamonti
authors.affiliation: Department of Infectious Diseases, Ente Ospedaliero Ospedali Galliera, Genova, Italy. Electronic address: giovanni.cenderello@galliera.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cenderello
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: veronica_pirriatore@hotmail.com.
authors.forename: Veronica
authors.initials: V
authors.lastname: Pirriatore
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: lauratrentini@yahoo.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Trentini
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: salassa@aslto2.piemonte.it.
authors.forename: Bernardino
authors.initials: B
authors.lastname: Salassa
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: bramato@tiscali.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Bramato
authors.affiliation: Department of Infectious Diseases, "Divisione A", Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: orofino@aslto2.piemonte.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Orofino
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: antonio.davolio@unito.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.affiliation: Infectious Diseases Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. Electronic address: mrizzi@hpg23.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Rizzi
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: giovanni.diperri@unito.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Unit of Infectious Diseases, University of Milano, Ospedale Luigi Sacco, Milano, Italy. Electronic address: stefano.rusconi@unimi.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rusconi
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Ospedale Amedeo di Savoia, Torino, Italy. Electronic address: stefano.bonora@unito.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D000069446:Atazanavir Sulfate / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010949:Plasma / Q000737:chemistry; D000068898:Raltegravir Potassium / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D012189:Retrospective Studies; D012641:Selection, Genetic; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate
keywords: Atazanavir; HIV; NRTI-sparing antiretroviral therapy; Raltegravir; Treatment-experienced patients