Class-sparing regimens for initial treatment of HIV-1 infection

Sharon A. Riddler, Richard Haubrich, A. Gregory DiRienzo, Lynne Peeples, William G. Powderly, Karin L. Klingman, Kevin W. Garren, Tania George, James F. Rooney, Barbara Brizz, Umesh G. Lalloo, Robert L. Murphy, Susan Swindells, Diane Havlir, John W. Mellors

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Abstract

Background: The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs. Methods: In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir-ritonavir plus two NRTIs (lopinavir-ritonavir group), and lopinavir-ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups. Results: At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group (P = 0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir-ritonavir group, and 83% in the NRTI-sparing group (P = 0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups. Conclusions: Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895.)

Original languageEnglish (US)
Pages (from-to)2095-2106
Number of pages12
JournalNew England Journal of Medicine
Volume358
Issue number20
DOIs
StatePublished - May 15 2008

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efavirenz
Lopinavir
Ritonavir
Reverse Transcriptase Inhibitors
Virus Diseases
Nucleosides
HIV-1
Therapeutics
Poisons
RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Riddler, S. A., Haubrich, R., DiRienzo, A. G., Peeples, L., Powderly, W. G., Klingman, K. L., ... Mellors, J. W. (2008). Class-sparing regimens for initial treatment of HIV-1 infection. New England Journal of Medicine, 358(20), 2095-2106. https://doi.org/10.1056/NEJMoa074609

Class-sparing regimens for initial treatment of HIV-1 infection. / Riddler, Sharon A.; Haubrich, Richard; DiRienzo, A. Gregory; Peeples, Lynne; Powderly, William G.; Klingman, Karin L.; Garren, Kevin W.; George, Tania; Rooney, James F.; Brizz, Barbara; Lalloo, Umesh G.; Murphy, Robert L.; Swindells, Susan; Havlir, Diane; Mellors, John W.

In: New England Journal of Medicine, Vol. 358, No. 20, 15.05.2008, p. 2095-2106.

Research output: Contribution to journalArticle

Riddler, SA, Haubrich, R, DiRienzo, AG, Peeples, L, Powderly, WG, Klingman, KL, Garren, KW, George, T, Rooney, JF, Brizz, B, Lalloo, UG, Murphy, RL, Swindells, S, Havlir, D & Mellors, JW 2008, 'Class-sparing regimens for initial treatment of HIV-1 infection', New England Journal of Medicine, vol. 358, no. 20, pp. 2095-2106. https://doi.org/10.1056/NEJMoa074609
Riddler SA, Haubrich R, DiRienzo AG, Peeples L, Powderly WG, Klingman KL et al. Class-sparing regimens for initial treatment of HIV-1 infection. New England Journal of Medicine. 2008 May 15;358(20):2095-2106. https://doi.org/10.1056/NEJMoa074609
Riddler, Sharon A. ; Haubrich, Richard ; DiRienzo, A. Gregory ; Peeples, Lynne ; Powderly, William G. ; Klingman, Karin L. ; Garren, Kevin W. ; George, Tania ; Rooney, James F. ; Brizz, Barbara ; Lalloo, Umesh G. ; Murphy, Robert L. ; Swindells, Susan ; Havlir, Diane ; Mellors, John W. / Class-sparing regimens for initial treatment of HIV-1 infection. In: New England Journal of Medicine. 2008 ; Vol. 358, No. 20. pp. 2095-2106.
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AU - Riddler, Sharon A.

AU - Haubrich, Richard

AU - DiRienzo, A. Gregory

AU - Peeples, Lynne

AU - Powderly, William G.

AU - Klingman, Karin L.

AU - Garren, Kevin W.

AU - George, Tania

AU - Rooney, James F.

AU - Brizz, Barbara

AU - Lalloo, Umesh G.

AU - Murphy, Robert L.

AU - Swindells, Susan

AU - Havlir, Diane

AU - Mellors, John W.

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N2 - Background: The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs. Methods: In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir-ritonavir plus two NRTIs (lopinavir-ritonavir group), and lopinavir-ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups. Results: At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group (P = 0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir-ritonavir group, and 83% in the NRTI-sparing group (P = 0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups. Conclusions: Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895.)

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