Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial
Jeffrey L. Lennox, Edwin DeJesus, Adriano Lazzarin, Richard B Pollard, Jose Valdez Ramalho Madruga, Daniel S. Berger, Jing Zhao, Xia Xu, Angela Williams-Diaz, Anthony J. Rodgers, Richard JO Barnard, Michael D. Miller, Mark J. DiNubile, Bach Yen Nguyen, Randi Leavitt, Peter Sklar
Background: Use of raltegravir with optimum background therapy is effective and well tolerated in treatment-experienced patients with multidrug-resistant HIV-1 infection. We compared the safety and efficacy of raltegravir with efavirenz as part of combination antiretroviral therapy for treatment-naive patients. Methods: Patients from 67 study centres on five continents were enrolled between Sept 14, 2006, and June 5, 2008. Eligible patients were infected with HIV-1, had viral RNA (vRNA) concentration of more than 5000 copies per mL, and no baseline resistance to efavirenz, tenofovir, or emtricitabine. Patients were randomly allocated by interactive voice response system in a 1:1 ratio (double-blind) to receive 400 mg oral raltegravir twice daily or 600 mg oral efavirenz once daily, in combination with tenofovir and emtricitabine. The primary efficacy endpoint was achievement of a vRNA concentration of less than 50 copies per mL at week 48. The primary analysis was per protocol. The margin of non-inferiority was 12%. This study is registered with ClinicalTrials.gov, number NCT00369941. Findings: 566 patients were enrolled and randomly allocated to treatment, of whom 281 received raltegravir, 282 received efavirenz, and three were never treated. At baseline, 297 (53%) patients had more than 100 000 vRNA copies per mL and 267 (47%) had CD4 counts of 200 cells per μL or less. The main analysis (with non-completion counted as failure) showed that 86·1% (n=241 patients) of the raltegravir group and 81·9% (n=230) of the efavirenz group achieved the primary endpoint (difference 4·2%, 95% CI -1·9 to 10·3). The time to achieve such viral suppression was shorter for patients on raltegravir than on efavirenz (log-rank test p<0·0001). Significantly fewer drug-related clinical adverse events occurred in patients on raltegravir (n=124 [44·1%]) than those on efavirenz (n=217 [77·0%]; difference -32·8%, 95% CI -40·2 to -25·0, p<0·0001). Serious drug-related clinical adverse events occurred in less than 2% of patients in each drug group. Interpretation: Raltegravir-based combination treatment had rapid and potent antiretroviral activity, which was non-inferior to that of efavirenz at week 48. Raltegravir is a well tolerated alternative to efavirenz as part of a combination regimen against HIV-1 in treatment-naive patients. Funding: Merck.
efavirenz
Tenofovir
Raltegravir Potassium
Lennox, J. L., DeJesus, E., Lazzarin, A., Pollard, R. B., Madruga, J. V. R., Berger, D. S., ... Sklar, P. (2009). Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. The Lancet, 374(9692), 796-806. https://doi.org/10.1016/S0140-6736(09)60918-1
Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection : a multicentre, double-blind randomised controlled trial. / Lennox, Jeffrey L.; DeJesus, Edwin; Lazzarin, Adriano; Pollard, Richard B; Madruga, Jose Valdez Ramalho; Berger, Daniel S.; Zhao, Jing; Xu, Xia; Williams-Diaz, Angela; Rodgers, Anthony J.; Barnard, Richard JO; Miller, Michael D.; DiNubile, Mark J.; Nguyen, Bach Yen; Leavitt, Randi; Sklar, Peter.
In: The Lancet, Vol. 374, No. 9692, 2009, p. 796-806.
Lennox, JL, DeJesus, E, Lazzarin, A, Pollard, RB, Madruga, JVR, Berger, DS, Zhao, J, Xu, X, Williams-Diaz, A, Rodgers, AJ, Barnard, RJO, Miller, MD, DiNubile, MJ, Nguyen, BY, Leavitt, R & Sklar, P 2009, 'Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial', The Lancet, vol. 374, no. 9692, pp. 796-806. https://doi.org/10.1016/S0140-6736(09)60918-1
Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JVR, Berger DS et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. The Lancet. 2009;374(9692):796-806. https://doi.org/10.1016/S0140-6736(09)60918-1
Lennox, Jeffrey L. ; DeJesus, Edwin ; Lazzarin, Adriano ; Pollard, Richard B ; Madruga, Jose Valdez Ramalho ; Berger, Daniel S. ; Zhao, Jing ; Xu, Xia ; Williams-Diaz, Angela ; Rodgers, Anthony J. ; Barnard, Richard JO ; Miller, Michael D. ; DiNubile, Mark J. ; Nguyen, Bach Yen ; Leavitt, Randi ; Sklar, Peter. / Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection : a multicentre, double-blind randomised controlled trial. In: The Lancet. 2009 ; Vol. 374, No. 9692. pp. 796-806.
@article{b8347fd59b194fe49c325ddb77496ac7,
title = "Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial",
abstract = "Background: Use of raltegravir with optimum background therapy is effective and well tolerated in treatment-experienced patients with multidrug-resistant HIV-1 infection. We compared the safety and efficacy of raltegravir with efavirenz as part of combination antiretroviral therapy for treatment-naive patients. Methods: Patients from 67 study centres on five continents were enrolled between Sept 14, 2006, and June 5, 2008. Eligible patients were infected with HIV-1, had viral RNA (vRNA) concentration of more than 5000 copies per mL, and no baseline resistance to efavirenz, tenofovir, or emtricitabine. Patients were randomly allocated by interactive voice response system in a 1:1 ratio (double-blind) to receive 400 mg oral raltegravir twice daily or 600 mg oral efavirenz once daily, in combination with tenofovir and emtricitabine. The primary efficacy endpoint was achievement of a vRNA concentration of less than 50 copies per mL at week 48. The primary analysis was per protocol. The margin of non-inferiority was 12{\%}. This study is registered with ClinicalTrials.gov, number NCT00369941. Findings: 566 patients were enrolled and randomly allocated to treatment, of whom 281 received raltegravir, 282 received efavirenz, and three were never treated. At baseline, 297 (53{\%}) patients had more than 100 000 vRNA copies per mL and 267 (47{\%}) had CD4 counts of 200 cells per μL or less. The main analysis (with non-completion counted as failure) showed that 86·1{\%} (n=241 patients) of the raltegravir group and 81·9{\%} (n=230) of the efavirenz group achieved the primary endpoint (difference 4·2{\%}, 95{\%} CI -1·9 to 10·3). The time to achieve such viral suppression was shorter for patients on raltegravir than on efavirenz (log-rank test p<0·0001). Significantly fewer drug-related clinical adverse events occurred in patients on raltegravir (n=124 [44·1{\%}]) than those on efavirenz (n=217 [77·0{\%}]; difference -32·8{\%}, 95{\%} CI -40·2 to -25·0, p<0·0001). Serious drug-related clinical adverse events occurred in less than 2{\%} of patients in each drug group. Interpretation: Raltegravir-based combination treatment had rapid and potent antiretroviral activity, which was non-inferior to that of efavirenz at week 48. Raltegravir is a well tolerated alternative to efavirenz as part of a combination regimen against HIV-1 in treatment-naive patients. Funding: Merck.",
author = "Lennox, {Jeffrey L.} and Edwin DeJesus and Adriano Lazzarin and Pollard, {Richard B} and Madruga, {Jose Valdez Ramalho} and Berger, {Daniel S.} and Jing Zhao and Xia Xu and Angela Williams-Diaz and Rodgers, {Anthony J.} and Barnard, {Richard JO} and Miller, {Michael D.} and DiNubile, {Mark J.} and Nguyen, {Bach Yen} and Randi Leavitt and Peter Sklar",
journal = "The Lancet",
T1 - Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection
T2 - a multicentre, double-blind randomised controlled trial
AU - Lennox, Jeffrey L.
AU - DeJesus, Edwin
AU - Lazzarin, Adriano
AU - Pollard, Richard B
AU - Madruga, Jose Valdez Ramalho
AU - Berger, Daniel S.
AU - Zhao, Jing
AU - Xu, Xia
AU - Williams-Diaz, Angela
AU - Rodgers, Anthony J.
AU - Barnard, Richard JO
AU - Miller, Michael D.
AU - DiNubile, Mark J.
AU - Nguyen, Bach Yen
AU - Leavitt, Randi
AU - Sklar, Peter
N2 - Background: Use of raltegravir with optimum background therapy is effective and well tolerated in treatment-experienced patients with multidrug-resistant HIV-1 infection. We compared the safety and efficacy of raltegravir with efavirenz as part of combination antiretroviral therapy for treatment-naive patients. Methods: Patients from 67 study centres on five continents were enrolled between Sept 14, 2006, and June 5, 2008. Eligible patients were infected with HIV-1, had viral RNA (vRNA) concentration of more than 5000 copies per mL, and no baseline resistance to efavirenz, tenofovir, or emtricitabine. Patients were randomly allocated by interactive voice response system in a 1:1 ratio (double-blind) to receive 400 mg oral raltegravir twice daily or 600 mg oral efavirenz once daily, in combination with tenofovir and emtricitabine. The primary efficacy endpoint was achievement of a vRNA concentration of less than 50 copies per mL at week 48. The primary analysis was per protocol. The margin of non-inferiority was 12%. This study is registered with ClinicalTrials.gov, number NCT00369941. Findings: 566 patients were enrolled and randomly allocated to treatment, of whom 281 received raltegravir, 282 received efavirenz, and three were never treated. At baseline, 297 (53%) patients had more than 100 000 vRNA copies per mL and 267 (47%) had CD4 counts of 200 cells per μL or less. The main analysis (with non-completion counted as failure) showed that 86·1% (n=241 patients) of the raltegravir group and 81·9% (n=230) of the efavirenz group achieved the primary endpoint (difference 4·2%, 95% CI -1·9 to 10·3). The time to achieve such viral suppression was shorter for patients on raltegravir than on efavirenz (log-rank test p<0·0001). Significantly fewer drug-related clinical adverse events occurred in patients on raltegravir (n=124 [44·1%]) than those on efavirenz (n=217 [77·0%]; difference -32·8%, 95% CI -40·2 to -25·0, p<0·0001). Serious drug-related clinical adverse events occurred in less than 2% of patients in each drug group. Interpretation: Raltegravir-based combination treatment had rapid and potent antiretroviral activity, which was non-inferior to that of efavirenz at week 48. Raltegravir is a well tolerated alternative to efavirenz as part of a combination regimen against HIV-1 in treatment-naive patients. Funding: Merck.
AB - Background: Use of raltegravir with optimum background therapy is effective and well tolerated in treatment-experienced patients with multidrug-resistant HIV-1 infection. We compared the safety and efficacy of raltegravir with efavirenz as part of combination antiretroviral therapy for treatment-naive patients. Methods: Patients from 67 study centres on five continents were enrolled between Sept 14, 2006, and June 5, 2008. Eligible patients were infected with HIV-1, had viral RNA (vRNA) concentration of more than 5000 copies per mL, and no baseline resistance to efavirenz, tenofovir, or emtricitabine. Patients were randomly allocated by interactive voice response system in a 1:1 ratio (double-blind) to receive 400 mg oral raltegravir twice daily or 600 mg oral efavirenz once daily, in combination with tenofovir and emtricitabine. The primary efficacy endpoint was achievement of a vRNA concentration of less than 50 copies per mL at week 48. The primary analysis was per protocol. The margin of non-inferiority was 12%. This study is registered with ClinicalTrials.gov, number NCT00369941. Findings: 566 patients were enrolled and randomly allocated to treatment, of whom 281 received raltegravir, 282 received efavirenz, and three were never treated. At baseline, 297 (53%) patients had more than 100 000 vRNA copies per mL and 267 (47%) had CD4 counts of 200 cells per μL or less. The main analysis (with non-completion counted as failure) showed that 86·1% (n=241 patients) of the raltegravir group and 81·9% (n=230) of the efavirenz group achieved the primary endpoint (difference 4·2%, 95% CI -1·9 to 10·3). The time to achieve such viral suppression was shorter for patients on raltegravir than on efavirenz (log-rank test p<0·0001). Significantly fewer drug-related clinical adverse events occurred in patients on raltegravir (n=124 [44·1%]) than those on efavirenz (n=217 [77·0%]; difference -32·8%, 95% CI -40·2 to -25·0, p<0·0001). Serious drug-related clinical adverse events occurred in less than 2% of patients in each drug group. Interpretation: Raltegravir-based combination treatment had rapid and potent antiretroviral activity, which was non-inferior to that of efavirenz at week 48. Raltegravir is a well tolerated alternative to efavirenz as part of a combination regimen against HIV-1 in treatment-naive patients. Funding: Merck.
JO - The Lancet
JF - The Lancet