Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression.

TitleRegimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression.
Publication TypeJournal Article
Year of Publication2006
AuthorsSwindells S, A DiRienzo G, Wilkin T, Fletcher CV, Margolis DM, Thal GD, Godfrey C, Bastow B, M Ray G, Wang H, Coombs RW, McKinnon J, Mellors JW
Corporate AuthorsAIDS Clinical Trials Group 5201 Study Team
JournalJAMA
Volume296
Issue7
Pagination806-14
Date Published2006 Aug 16
ISSN1538-3598
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Atazanavir Sulfate, CD4 Lymphocyte Count, Female, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Male, Middle Aged, Oligopeptides, Patient Compliance, Pilot Projects, Pyridines, Ritonavir, RNA, Messenger, Viral Load
Abstract

CONTEXT: The long-term adverse effects, expense, and difficulty of adherence to antiretroviral regimens have led to studies of simpler maintenance therapies. Maintenance therapy with ritonavir-boosted atazanavir alone is a possible option because of low pill burden, once-daily dosing, safety, and unique resistance profile.

OBJECTIVE: To assess whether simplified maintenance therapy with atazanavir-ritonavir alone after virologic suppression increases the risk of virologic failure (2 consecutive human immunodeficiency virus type 1 [HIV-1] RNA measurements of > or =200 copies/mL).

DESIGN, SETTING, AND PARTICIPANTS: Single-group, open-label, multicenter, 24-week pilot study of 36 HIV-infected adults with virologic suppression for 48 weeks or longer receiving their first protease inhibitor (PI)-based regimen. The study was conducted between September 1, 2004, and April 18, 2006, at 12 participating AIDS clinical trial units in the United States.

INTERVENTION: Participants switched PIs to atazanavir-ritonavir at entry and discontinued nucleoside analog reverse transcriptase inhibitors (NRTIs) after 6 weeks.

MAIN OUTCOME MEASURES: Virologic failure within 24 weeks of discontinuing NRTIs. Other measures included HIV-1 drug resistance, plasma atazanavir concentrations, adverse events, CD4 cell counts, plasma lipid levels, and HIV-1 RNA levels in seminal plasma.

RESULTS: Thirty-six participants enrolled and 2 discontinued before simplification to atazanavir-ritonavir alone. Thirty-four patients were included in the analysis of the primary end point after 24 weeks: 1 withdrew voluntarily, and 33 continued the regimen. Virologic success (absence of failure) through 24 weeks of simplified therapy occurred in 91% (31 of 34 patients; lower 90% confidence interval limit = 85%). Three participants experienced virologic failure 12, 14, and 20 weeks after simplification, with plasma HIV-1 RNA levels of 4730, 1285, and 28 397 copies/mL, respectively. Resistance testing at failure did not identify PI resistance mutations. Plasma atazanavir concentrations at failure were low or below detection in 2 of 3 participants experiencing failure. There were no treatment discontinuations for adverse events after simplification; no significant changes in CD4 cell counts or plasma lipid levels; and no detectable HIV-1 RNA in seminal plasma from all 8 participants tested.

CONCLUSIONS: These preliminary data suggest that simplified maintenance therapy with atazanavir-ritonavir alone may be efficacious for maintaining virologic suppression in carefully selected patients with HIV infection. These findings require confirmation in larger, randomized trials of this strategy.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00084019.

DOI10.1001/jama.296.7.806
Alternate JournalJAMA
PubMed ID16905786
Grant ListAI25868 / AI / NIAID NIH HHS / United States
AI25897 / AI / NIAID NIH HHS / United States
AI27661 / AI / NIAID NIH HHS / United States
AI27666 / AI / NIAID NIH HHS / United States
AI32770 / AI / NIAID NIH HHS / United States
AI34832 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI39156 / AI / NIAID NIH HHS / United States
AI46376 / AI / NIAID NIH HHS / United States
AI46383 / AI / NIAID NIH HHS / United States
AI46386 / AI / NIAID NIH HHS / United States
KL2 TR000146 / TR / NCATS NIH HHS / United States
U01 AI38858 / AI / NIAID NIH HHS / United States