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A nucleoside- and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naïve HIV-infected patients: SPARTAN study results.

TitleA nucleoside- and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naïve HIV-infected patients: SPARTAN study results.
Publication TypeJournal Article
Year of Publication2012
AuthorsKozal MJ, Lupo S, Dejesus E, Molina J-, McDonald C, Raffi F, Benetucci J, Mancini M, Yang R, Wirtz V, Percival L, Zhang J, Zhu L, Arikan D, Farajallah A, Nguyen B-, Leavitt R, McGrath D, Lataillade M
JournalHIV Clin Trials
Volume13
Issue3
Pagination119-30
Date Published2012 May-Jun
ISSN1528-4336
KeywordsAdult, Anti-HIV Agents, Atazanavir Sulfate, CD4 Lymphocyte Count, DNA, Viral, Drug Resistance, Viral, Drug Therapy, Combination, Female, HIV Infections, Humans, Lipids, Male, Nucleosides, Oligopeptides, Pyridines, Pyrrolidinones, Raltegravir Potassium, Ritonavir
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.

DOI10.1310/hct1303-119
Alternate JournalHIV Clin Trials
PubMed ID22592092