Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients.
BACKGROUND
Atazanavir (ATV), the first once-daily protease inhibitor approved for the treatment of HIV-1 infection, is recommended for use in antiretroviral (ARV) treatment-naive and -experienced patients. Study AI424-089 was a prospective, randomized, open-label, 96-week study comparing 2 ATV-based treatment regimens in ARV-naive HIV-infected patients.


METHODS
Adults with HIV RNA levels > or =2000 copies/mL were randomized (1:1) to once-daily ATV at a dose of 300 mg with ritonavir at a dose of 100 mg (ATV300/RTV) or ATV at a dose of 400 mg (ATV400); both regimens included lamivudine and an investigational extended-release formulation of stavudine. The primary endpoint for this noninferiority study was the proportion of patients (response rate) with an HIV RNA load <400 copies/mL at week 48.


RESULTS
Response rates at week 48 were 86% and 85% on the ATV300/RTV and ATV400 regimens, respectively (difference estimate [95% confidence interval] = 1.5 [-8.2 to 11.1]). There were 3 and 10 patients with virologic failure in the ATV300/RTV and ATV400 groups, respectively. One patient (ATV400) developed phenotypic resistance to ATV associated with an I50L substitution. Adverse event-related discontinuations were 8% among ATV300/RTV-treated patients and <1% among ATV400-treated patients. Plasma lipid elevations were low with both regimens. Both regimens were well tolerated.


CONCLUSIONS
These findings demonstrate the safety and efficacy of the ATV300/RTV regimen and confirm the safety and efficacy of ATV400 in an ARV-naive patient population.
Malan
D R
DR
Triple M Research, Port Elizabeth, South Africa. nielm@iafrica.com
Krantz
Edrich
E
David
Neal
N
Wirtz
Victoria
V
Hammond
Janet
J
McGrath
Donnie
D
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use; D019562:Viral Load; D028761:Withholding Treatment
D019380:Anti-HIV Agents; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D019259:Lamivudine; D000069446:Atazanavir Sulfate; D018119:Stavudine; D019438:Ritonavir