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, AIDS Clinical Trials Group Study A5142 Team, P Cain, M Cooper, M Dobson, M Dorosh, P Kondo, D Rusin, K Squires, P Tran, S Brun, R Rode, M Poblenz, M Hitchcock, K Coleman, B Sha, O Adeyemi, W K Henry, W Calvert, M Morgan, B Jackson, M Goldman, J Hernandez, H H Bolivar, M A Fischl, C J Fichtenbaum, J Baer, S Byars, M Stewart, M Edmondson-Melancon, C A Funk, J N Connor, M Torres, W E Maher, L Laughlin, M Adams, C Hurley, Z Zelasky, D Wohl, D McMahon, B Rutecki, P Kumar, I Vvedenskaya, G M Cox, D Wade, P Sax, J Gothing, A A Amod, B Rodriguez, B Philpotts, H Friedman, A Thomas, B Putnam, C Basler, W A O'Brien, G Casey, I Wiggins, G Casey, M Carlson, E Daar, A Olusanya, M Schreiber, C Davis, B Boyce, G-Y Kim, K Gray, J Volinski, J Norris, S Valle, J Hoffman, S Cahill, D Garmon, D Mildvan, J Forcht, C Gonzalez, K Tashima, D Perez, P Keiser, T Petersen, N Hanks, S Souza, A C Collier, S Storey, V Hughes, T Stroberg, G Smith, I Ofotokun, 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, AIDS Clinical Trials Group Study A5142 Team, P Cain, M Cooper, M Dobson, M Dorosh, P Kondo, D Rusin, K Squires, P Tran, S Brun, R Rode, M Poblenz, M Hitchcock, K Coleman, B Sha, O Adeyemi, W K Henry, W Calvert, M Morgan, B Jackson, M Goldman, J Hernandez, H H Bolivar, M A Fischl, C J Fichtenbaum, J Baer, S Byars, M Stewart, M Edmondson-Melancon, C A Funk, J N Connor, M Torres, W E Maher, L Laughlin, M Adams, C Hurley, Z Zelasky, D Wohl, D McMahon, B Rutecki, P Kumar, I Vvedenskaya, G M Cox, D Wade, P Sax, J Gothing, A A Amod, B Rodriguez, B Philpotts, H Friedman, A Thomas, B Putnam, C Basler, W A O'Brien, G Casey, I Wiggins, G Casey, M Carlson, E Daar, A Olusanya, M Schreiber, C Davis, B Boyce, G-Y Kim, K Gray, J Volinski, J Norris, S Valle, J Hoffman, S Cahill, D Garmon, D Mildvan, J Forcht, C Gonzalez, K Tashima, D Perez, P Keiser, T Petersen, N Hanks, S Souza, A C Collier, S Storey, V Hughes, T Stroberg, G Smith, I Ofotokun
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 [ClinicalTrials.gov].).
Conflict of interest statement
No other potential conflict of interest relevant to this article was reported.
Copyright 2008 Massachusetts Medical Society.
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Source: PubMed