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

Susan Swindells, A. Gregory DiRienzo, Timothy Wilkin, Courtney V Fletcher, David M. Margolis, Gary D. Thal, Catherine Godfrey, Barbara Bastow, M. Graham Ray, Hongying Wang, Robert W. Coombs, John McKinnon, John W. Mellors

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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 ≥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.

Original languageEnglish (US)
Pages (from-to)806-814
Number of pages9
JournalJournal of the American Medical Association
Volume296
Issue number7
DOIs
StatePublished - Aug 16 2006

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Ritonavir
Maintenance
HIV-1
RNA
Reverse Transcriptase Inhibitors
CD4 Lymphocyte Count
Semen
Protease Inhibitors
Nucleosides
Therapeutics
Lipids
Atazanavir Sulfate
Drug Resistance
HIV Infections
Acquired Immunodeficiency Syndrome
Outcome Assessment (Health Care)
Clinical Trials
HIV
Confidence Intervals
Safety

ASJC Scopus subject areas

  • Medicine(all)

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Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression. / Swindells, Susan; DiRienzo, A. Gregory; Wilkin, Timothy; Fletcher, Courtney V; Margolis, David M.; Thal, Gary D.; Godfrey, Catherine; Bastow, Barbara; Ray, M. Graham; Wang, Hongying; Coombs, Robert W.; McKinnon, John; Mellors, John W.

In: Journal of the American Medical Association, Vol. 296, No. 7, 16.08.2006, p. 806-814.

Research output: Contribution to journalArticle

Swindells, S, DiRienzo, AG, Wilkin, T, Fletcher, CV, Margolis, DM, Thal, GD, Godfrey, C, Bastow, B, Ray, MG, Wang, H, Coombs, RW, McKinnon, J & Mellors, JW 2006, 'Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression', Journal of the American Medical Association, vol. 296, no. 7, pp. 806-814. https://doi.org/10.1001/jama.296.7.806
Swindells, Susan ; DiRienzo, A. Gregory ; Wilkin, Timothy ; Fletcher, Courtney V ; Margolis, David M. ; Thal, Gary D. ; Godfrey, Catherine ; Bastow, Barbara ; Ray, M. Graham ; Wang, Hongying ; Coombs, Robert W. ; McKinnon, John ; Mellors, John W. / Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression. In: Journal of the American Medical Association. 2006 ; Vol. 296, No. 7. pp. 806-814.
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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 ≥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.",
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AU - Fletcher, Courtney V

AU - Margolis, David M.

AU - Thal, Gary D.

AU - Godfrey, Catherine

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N2 - 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 ≥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.

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