Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1: A randomized trial

Eric S. Daar, Camlin Tierney, Margaret A Fischl, Paul E. Sax, Katie Mollan, Chakra Budhathoki, Catherine Godfrey, Nasreen C. Jahed, Laurie Myers, David Katzenstein, Awny Farajallah, James F. Rooney, Keith A. Pappa, William C. Woodward, Kristine Patterson, Hector Bolivar, Constance A. Benson, Ann C. Collier

Research output: Contribution to journalArticle

252 Citations (Scopus)

Abstract

Background: Limited data compare once-daily options for initial therapy for HIV-1.Objective: To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.Design: A randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks. Regimens were assigned by using a central computer, stratified by screening HIV-1 RNA level less than 100 000 copies/mL or 100 000 copies/mL or greater; blinding was known only to the site pharmacist. (ClinicalTrials.gov registration number: NCT00118898)Setting: 59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.Patients: Antiretroviral-naive patients.Intervention: Open-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.Measurements: Primary outcomes were time to virologic failure, safety, and tolerability events. Secondary end points included proportion of patients with HIV-1 RNA level less than 50 copies/mL, emergence of drug resistance, changes in CD4 cell counts, calculated creatinine clearance, and lipid levels.Results: 463 eligible patients were randomly assigned to receive atazanavir plus ritonavir and 465 were assigned to receive efavirenz, both with abacavir-lamivudine; 322 (70%)and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF-emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received atazanavir plus ritonavir and and the group that received efavirenz and did not differ according to whether abacavir-lamivudine or tenofovir DF-emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P = 0.048) and tolerability (P < 0.001) events was longer in persons given atazanavir plus ritonavir than in those given efavirenz with abacavir-lamivudine but not with tenofovir DF-emtricitabine.Limitations: Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, atazanavir plus ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug.Conclusion: Atazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine. Primary Funding Source: National Institutes of Health.

Original languageEnglish
Pages (from-to)445-456
Number of pages12
JournalAnnals of Internal Medicine
Volume154
Issue number7
StatePublished - Apr 1 2011

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efavirenz
Tenofovir
Ritonavir
HIV-1
Pharmaceutical Preparations
Safety
Therapeutics
RNA
Puerto Rico
Reverse Transcriptase Inhibitors
HLA-B Antigens
National Institutes of Health (U.S.)
Standard of Care
CD4 Lymphocyte Count
Atazanavir Sulfate
Viral Load
Nucleosides
Pharmacists
Drug Resistance
Signs and Symptoms

ASJC Scopus subject areas

  • Internal Medicine

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Daar, E. S., Tierney, C., Fischl, M. A., Sax, P. E., Mollan, K., Budhathoki, C., ... Collier, A. C. (2011). Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1: A randomized trial. Annals of Internal Medicine, 154(7), 445-456.

Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1 : A randomized trial. / Daar, Eric S.; Tierney, Camlin; Fischl, Margaret A; Sax, Paul E.; Mollan, Katie; Budhathoki, Chakra; Godfrey, Catherine; Jahed, Nasreen C.; Myers, Laurie; Katzenstein, David; Farajallah, Awny; Rooney, James F.; Pappa, Keith A.; Woodward, William C.; Patterson, Kristine; Bolivar, Hector; Benson, Constance A.; Collier, Ann C.

In: Annals of Internal Medicine, Vol. 154, No. 7, 01.04.2011, p. 445-456.

Research output: Contribution to journalArticle

Daar, ES, Tierney, C, Fischl, MA, Sax, PE, Mollan, K, Budhathoki, C, Godfrey, C, Jahed, NC, Myers, L, Katzenstein, D, Farajallah, A, Rooney, JF, Pappa, KA, Woodward, WC, Patterson, K, Bolivar, H, Benson, CA & Collier, AC 2011, 'Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1: A randomized trial', Annals of Internal Medicine, vol. 154, no. 7, pp. 445-456.
Daar, Eric S. ; Tierney, Camlin ; Fischl, Margaret A ; Sax, Paul E. ; Mollan, Katie ; Budhathoki, Chakra ; Godfrey, Catherine ; Jahed, Nasreen C. ; Myers, Laurie ; Katzenstein, David ; Farajallah, Awny ; Rooney, James F. ; Pappa, Keith A. ; Woodward, William C. ; Patterson, Kristine ; Bolivar, Hector ; Benson, Constance A. ; Collier, Ann C. / Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1 : A randomized trial. In: Annals of Internal Medicine. 2011 ; Vol. 154, No. 7. pp. 445-456.
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abstract = "Background: Limited data compare once-daily options for initial therapy for HIV-1.Objective: To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.Design: A randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks. Regimens were assigned by using a central computer, stratified by screening HIV-1 RNA level less than 100 000 copies/mL or 100 000 copies/mL or greater; blinding was known only to the site pharmacist. (ClinicalTrials.gov registration number: NCT00118898)Setting: 59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.Patients: Antiretroviral-naive patients.Intervention: Open-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.Measurements: Primary outcomes were time to virologic failure, safety, and tolerability events. Secondary end points included proportion of patients with HIV-1 RNA level less than 50 copies/mL, emergence of drug resistance, changes in CD4 cell counts, calculated creatinine clearance, and lipid levels.Results: 463 eligible patients were randomly assigned to receive atazanavir plus ritonavir and 465 were assigned to receive efavirenz, both with abacavir-lamivudine; 322 (70{\%})and 324 (70{\%}), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF-emtricitabine were 465 and 464; 342 (74{\%}) and 343 (74{\%}) completed follow-up. Primary efficacy was similar in the group that received atazanavir plus ritonavir and and the group that received efavirenz and did not differ according to whether abacavir-lamivudine or tenofovir DF-emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95{\%} CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P = 0.048) and tolerability (P < 0.001) events was longer in persons given atazanavir plus ritonavir than in those given efavirenz with abacavir-lamivudine but not with tenofovir DF-emtricitabine.Limitations: Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, atazanavir plus ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32{\%} of patients modified or discontinued treatment with their third drug.Conclusion: Atazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine. Primary Funding Source: National Institutes of Health.",
author = "Daar, {Eric S.} and Camlin Tierney and Fischl, {Margaret A} and Sax, {Paul E.} and Katie Mollan and Chakra Budhathoki and Catherine Godfrey and Jahed, {Nasreen C.} and Laurie Myers and David Katzenstein and Awny Farajallah and Rooney, {James F.} and Pappa, {Keith A.} and Woodward, {William C.} and Kristine Patterson and Hector Bolivar and Benson, {Constance A.} and Collier, {Ann C.}",
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TY - JOUR

T1 - Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1

T2 - A randomized trial

AU - Daar, Eric S.

AU - Tierney, Camlin

AU - Fischl, Margaret A

AU - Sax, Paul E.

AU - Mollan, Katie

AU - Budhathoki, Chakra

AU - Godfrey, Catherine

AU - Jahed, Nasreen C.

AU - Myers, Laurie

AU - Katzenstein, David

AU - Farajallah, Awny

AU - Rooney, James F.

AU - Pappa, Keith A.

AU - Woodward, William C.

AU - Patterson, Kristine

AU - Bolivar, Hector

AU - Benson, Constance A.

AU - Collier, Ann C.

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Background: Limited data compare once-daily options for initial therapy for HIV-1.Objective: To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.Design: A randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks. Regimens were assigned by using a central computer, stratified by screening HIV-1 RNA level less than 100 000 copies/mL or 100 000 copies/mL or greater; blinding was known only to the site pharmacist. (ClinicalTrials.gov registration number: NCT00118898)Setting: 59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.Patients: Antiretroviral-naive patients.Intervention: Open-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.Measurements: Primary outcomes were time to virologic failure, safety, and tolerability events. Secondary end points included proportion of patients with HIV-1 RNA level less than 50 copies/mL, emergence of drug resistance, changes in CD4 cell counts, calculated creatinine clearance, and lipid levels.Results: 463 eligible patients were randomly assigned to receive atazanavir plus ritonavir and 465 were assigned to receive efavirenz, both with abacavir-lamivudine; 322 (70%)and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF-emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received atazanavir plus ritonavir and and the group that received efavirenz and did not differ according to whether abacavir-lamivudine or tenofovir DF-emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P = 0.048) and tolerability (P < 0.001) events was longer in persons given atazanavir plus ritonavir than in those given efavirenz with abacavir-lamivudine but not with tenofovir DF-emtricitabine.Limitations: Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, atazanavir plus ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug.Conclusion: Atazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine. Primary Funding Source: National Institutes of Health.

AB - Background: Limited data compare once-daily options for initial therapy for HIV-1.Objective: To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.Design: A randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks. Regimens were assigned by using a central computer, stratified by screening HIV-1 RNA level less than 100 000 copies/mL or 100 000 copies/mL or greater; blinding was known only to the site pharmacist. (ClinicalTrials.gov registration number: NCT00118898)Setting: 59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.Patients: Antiretroviral-naive patients.Intervention: Open-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.Measurements: Primary outcomes were time to virologic failure, safety, and tolerability events. Secondary end points included proportion of patients with HIV-1 RNA level less than 50 copies/mL, emergence of drug resistance, changes in CD4 cell counts, calculated creatinine clearance, and lipid levels.Results: 463 eligible patients were randomly assigned to receive atazanavir plus ritonavir and 465 were assigned to receive efavirenz, both with abacavir-lamivudine; 322 (70%)and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF-emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received atazanavir plus ritonavir and and the group that received efavirenz and did not differ according to whether abacavir-lamivudine or tenofovir DF-emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P = 0.048) and tolerability (P < 0.001) events was longer in persons given atazanavir plus ritonavir than in those given efavirenz with abacavir-lamivudine but not with tenofovir DF-emtricitabine.Limitations: Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, atazanavir plus ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug.Conclusion: Atazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine. Primary Funding Source: National Institutes of Health.

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