Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression.
JAMA
; 296(7): 806-14, 2006 Aug 16.
Article
em En
| MEDLINE
| ID: mdl-16905786
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, ANDPARTICIPANTS:
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 OUTCOMEMEASURES:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Piridinas
/
Infecções por HIV
/
Inibidores da Protease de HIV
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Ritonavir
/
Fármacos Anti-HIV
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article