title: A nucleoside- and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naïve HIV-infected patients: SPARTAN study results.
abstract: BACKGROUND
  Nucleoside and ritonavir (RTV) toxicities have led to increased interest in nucleoside reverse transcriptase inhibitors (NRTIs) and RTV-sparing antiretroviral regimens. SPARTAN was a multicenter, randomized, open-label, noncomparative pilot study evaluating the efficacy, safety, and resistance profile of an investigational NRTI- and RTV-sparing regimen (experimental atazanavir [ATV] dose 300 mg bid + raltegravir [RAL] 400 mg bid [ATV+RAL]). The reference regimen consisted of ATV 300 mg/RTV 100 mg qd + tenofovir (TDF) 300 mg/emtricitabine (FTC) 200 mg qd (ATV/r+TDF/FTC).
  
  
  METHODS
  Treatment-naïve HIV-infected patients with HIV-RNA ≥5,000 copies/mL were randomized 2:1 to receive twice-daily ATV+RAL (n=63) or once-daily ATV/r+TDF/FTC (n=31). Efficacy at 24 weeks was determined by confirmed virologic response (CVR; HIV-RNA <50 copies/mL) with noncom-pleters counted as failures based on all treated subjects.
  
  
  RESULTS
  The proportion of patients with CVR HIV RNA <50 copies/mL at week 24 was 74.6% (47/63) in the ATV+RAL arm and 63.3% (19/30) in the ATV/r+TDF/FTC arm. Systemic exposure to ATV in the ATV+RAL regimen was higher than historically observed with ATV/r+TDF/ FTC. Incidence of Grade 4 hyperbilirubinemia was higher on ATV+RAL (20.6%; 13/63) than on ATV/r+TDF/FTC (0%). The criteria for resistance testing (virologic failure [VF]: HIV-RNA ≥400 copies/mL) was met in 6/63 patients on ATV+RAL, and 1/30 on ATV/r+TDF/FTC; 4 VFs on ATV+RAL developed RAL resistance.
  
  
  CONCLUSIONS
  ATV+RAL, an experimental NRTI- and RTV-sparing regimen, achieved virologic suppression rates comparable to current standards of care for treatment-naïve patients. The overall profile did not appear optimal for further clinical development given its development of resistance to RAL and higher rates of hyperbilirubinemia with twice-daily ATV compared with ATV/RTV.
authors.affiliation: Yale University School of Medicine and VA CT Healthcare System, New Haven, Connecticut, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kozal
authors.forename: Sergio
authors.initials: S
authors.lastname: Lupo
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Cheryl
authors.initials: C
authors.lastname: McDonald
authors.forename: Francois
authors.initials: F
authors.lastname: Raffi
authors.forename: Jorge
authors.initials: J
authors.lastname: Benetucci
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Victoria
authors.initials: V
authors.lastname: Wirtz
authors.forename: Lisa
authors.initials: L
authors.lastname: Percival
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Dilek
authors.initials: D
authors.lastname: Arikan
authors.forename: Awny
authors.initials: A
authors.lastname: Farajallah
authors.forename: Bach-Yen
authors.initials: BY
authors.lastname: Nguyen
authors.forename: Randi
authors.initials: R
authors.lastname: Leavitt
authors.forename: Donnie
authors.initials: D
authors.lastname: McGrath
authors.forename: Max
authors.initials: M
authors.lastname: Lataillade
authors.lastname: The Spartan Study Team
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D009705:Nucleosides / Q000627:therapeutic use*; D009842:Oligopeptides / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D011760:Pyrrolidinones / Q000008:administration & dosage*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D008055:Lipids; D009705:Nucleosides; D009842:Oligopeptides; D011725:Pyridines; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate; D019438:Ritonavir