Comparison of Sequential Three-Drug Regimens as Initial Therapy for HIV-1 Infection

Gregory K. Robbins, Victor De Gruttola, Robert W. Shafer, Laura M. Smeaton, Sally W. Snyder, Carla Pettinelli, Michael P. Dubé, Margaret A. Fischl, Richard B Pollard, Robert Delapenha, Linda Gedeon, Charles Van Der Horst, Robert L. Murphy, Mark I. Becker, Richard T. D'Aquila, Stefano Vella, Thomas C. Merigan, Martin S. Hirsch

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

BACKGROUND: The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies. METHODS: This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen. RESULTS: A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression. CONCLUSIONS: The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study.

Original languageEnglish (US)
Pages (from-to)2293-2303
Number of pages11
JournalNew England Journal of Medicine
Volume349
Issue number24
DOIs
StatePublished - Dec 11 2003

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efavirenz
Lamivudine
Zidovudine
Virus Diseases
HIV-1
Nelfinavir
Stavudine
Didanosine
Pharmaceutical Preparations
Therapeutics
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Robbins, G. K., De Gruttola, V., Shafer, R. W., Smeaton, L. M., Snyder, S. W., Pettinelli, C., ... Hirsch, M. S. (2003). Comparison of Sequential Three-Drug Regimens as Initial Therapy for HIV-1 Infection. New England Journal of Medicine, 349(24), 2293-2303. https://doi.org/10.1056/NEJMoa030264

Comparison of Sequential Three-Drug Regimens as Initial Therapy for HIV-1 Infection. / Robbins, Gregory K.; De Gruttola, Victor; Shafer, Robert W.; Smeaton, Laura M.; Snyder, Sally W.; Pettinelli, Carla; Dubé, Michael P.; Fischl, Margaret A.; Pollard, Richard B; Delapenha, Robert; Gedeon, Linda; Van Der Horst, Charles; Murphy, Robert L.; Becker, Mark I.; D'Aquila, Richard T.; Vella, Stefano; Merigan, Thomas C.; Hirsch, Martin S.

In: New England Journal of Medicine, Vol. 349, No. 24, 11.12.2003, p. 2293-2303.

Research output: Contribution to journalArticle

Robbins, GK, De Gruttola, V, Shafer, RW, Smeaton, LM, Snyder, SW, Pettinelli, C, Dubé, MP, Fischl, MA, Pollard, RB, Delapenha, R, Gedeon, L, Van Der Horst, C, Murphy, RL, Becker, MI, D'Aquila, RT, Vella, S, Merigan, TC & Hirsch, MS 2003, 'Comparison of Sequential Three-Drug Regimens as Initial Therapy for HIV-1 Infection', New England Journal of Medicine, vol. 349, no. 24, pp. 2293-2303. https://doi.org/10.1056/NEJMoa030264
Robbins GK, De Gruttola V, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C et al. Comparison of Sequential Three-Drug Regimens as Initial Therapy for HIV-1 Infection. New England Journal of Medicine. 2003 Dec 11;349(24):2293-2303. https://doi.org/10.1056/NEJMoa030264
Robbins, Gregory K. ; De Gruttola, Victor ; Shafer, Robert W. ; Smeaton, Laura M. ; Snyder, Sally W. ; Pettinelli, Carla ; Dubé, Michael P. ; Fischl, Margaret A. ; Pollard, Richard B ; Delapenha, Robert ; Gedeon, Linda ; Van Der Horst, Charles ; Murphy, Robert L. ; Becker, Mark I. ; D'Aquila, Richard T. ; Vella, Stefano ; Merigan, Thomas C. ; Hirsch, Martin S. / Comparison of Sequential Three-Drug Regimens as Initial Therapy for HIV-1 Infection. In: New England Journal of Medicine. 2003 ; Vol. 349, No. 24. pp. 2293-2303.
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T1 - Comparison of Sequential Three-Drug Regimens as Initial Therapy for HIV-1 Infection

AU - Robbins, Gregory K.

AU - De Gruttola, Victor

AU - Shafer, Robert W.

AU - Smeaton, Laura M.

AU - Snyder, Sally W.

AU - Pettinelli, Carla

AU - Dubé, Michael P.

AU - Fischl, Margaret A.

AU - Pollard, Richard B

AU - Delapenha, Robert

AU - Gedeon, Linda

AU - Van Der Horst, Charles

AU - Murphy, Robert L.

AU - Becker, Mark I.

AU - D'Aquila, Richard T.

AU - Vella, Stefano

AU - Merigan, Thomas C.

AU - Hirsch, Martin S.

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Y1 - 2003/12/11

N2 - BACKGROUND: The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies. METHODS: This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen. RESULTS: A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression. CONCLUSIONS: The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study.

AB - BACKGROUND: The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies. METHODS: This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen. RESULTS: A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression. CONCLUSIONS: The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study.

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