title: The safety, efficacy, and pharmacokinetic profile of a switch in antiretroviral therapy to saquinavir, ritonavir, and atazanavir alone for 48 weeks and a switch in the saquinavir formulation.
abstract: BACKGROUND
  Toxicities observed with current combination antiretroviral therapy (CART) warrant a search for novel options, such as class-sparing regimens. Ritonavir-boosted double-protease inhibitor (PI)-only regimens are such an option but are prone to pharmacokinetic interactions.
  
  
  METHODS
  This 48-week randomized study examined the safety and efficacy of a switch in CART to a once-daily regimen of saquinavir (SQV), ritonavir (RTV), and atazanavir (ATV) that did not include nucleoside reverse-transcriptase inhibitors (NRTIs). The study also assessed the pharmacokinetic profile of a change in the SQV formulation, from 200 mg to 500 mg, in 2 regimens (SQV-RTV twice per day plus NRTIs [arm 1] and SQV-RTV-ATV once per day without NRTIs [arm 2]) in human immunodeficiency virus type 1-infected subjects (plasma human immunodeficiency virus RNA level, <50 copies/mL). Patients underwent an initial SQV formulation change or a CART change to SQV-RTV-ATV with intense pharmacokinetic sampling. All patients were subsequently assigned to receive SQV-RTV-ATV (1500, 100, and 300 mg once per day, respectively) without NRTIs for 48 weeks. The primary end point was the percentage of patients who experienced virologic failure.
  
  
  RESULTS
  Of 25 subjects enrolled, scleral icterus was the most common adverse event (3 patients [12.5%]). Three subjects (12.5%) experienced virologic failure; and mean (+/- standard error of the mean) increase in the CD4(+) lymphocyte count was 63 +/- 36 cells/ mu L over 48 weeks (P=.012). The SQV geometric mean area under the time curve parameters were not significantly altered for the 2 SQV formulations (arm 1, 23.32 vs. 18.76 ngxh/mL [geometric mean ratio, 0.80] for the 200-mg vs. 500-mg formulations, respectively; arm 2, 50.31 vs. 44.79 ngxh/mL [geometric mean ratio, 0.88], for the 200-mg vs. 500-mg formulations, respectively).
  
  
  CONCLUSIONS
  A CART regimen of SQV-RTV-ATV alone demonstrated sustained virologic efficacy and was associated with significant increases in the CD4(+) lymphocyte count.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. a.winston@imperial.ac.uk
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.forename: Patrick W G
authors.initials: PW
authors.lastname: Mallon
authors.forename: Claudette
authors.initials: C
authors.lastname: Satchell
authors.forename: Karen
authors.initials: K
authors.lastname: MacRae
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Williams
authors.forename: Malte
authors.initials: M
authors.lastname: Schutz
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019258:Saquinavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019258:Saquinavir; D019438:Ritonavir