• Robert W Shafer, Laura M Smeaton, Gregory K Robbins, Victor De Gruttola, Sally W Snyder, Richard T D'Aquila, Victoria A Johnson, Gene D Morse, Mostafa A Nokta, Ana I Martinez, Barbara M Gripshover, Pamposh Kaul, Richard Haubrich, Mary Swingle, S Debra McCarty, Stefano Vella, Martin S Hirsch, Thomas C Merigan, and AIDS Clinical Trials Group 384 Team.
• Stanford University Medical Center, Stanford, Calif, USA. grobbins@partners.org
• N. Engl. J. Med. 2003 Dec 11; 349 (24): 230423152304-15.

BackgroundIt is unclear whether therapy for human immunodeficiency virus type 1 (HIV-1) should be initiated with a four-drug or two sequential three-drug regimens.MethodsIn this multicenter trial we compared initial therapy involving four-drug regimens containing efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine and lamivudine with therapy involving two consecutive three-drug regimens the first of which contained either efavirenz or nelfinavir.ResultsA total of 980 subjects were followed for a median of 2.3 years. There was no significant difference in the occurrence of regimen failures between the group that received the four-drug regimen containing didanosine, stavudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with didanosine, stavudine, and nelfinavir (hazard ratio for regimen failure, 1.24) or didanosine, stavudine, and efavirenz (hazard ratio, 1.01). There was no significant difference between the group that received the four-drug regimen containing zidovudine, lamivudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with zidovudine, lamivudine, and nelfinavir (hazard ratio, 1.06) or zidovudine, lamivudine, and efavirenz (hazard ratio, 1.45). A four-drug regimen was associated with a longer time to the first regimen failure than the three-drug regimens containing didanosine, stavudine, and nelfinavir (hazard ratio for a first regimen failure, 0.55); didanosine, stavudine, and efavirenz (hazard ratio, 0.63); or zidovudine, lamivudine, and nelfinavir (hazard ratio, 0.49), but not the three-drug regimen containing zidovudine, lamivudine, and efavirenz (hazard ratio, 1.21).ConclusionsThere was no significant difference in the duration of successful HIV-1 treatment between a single four-drug regimen and two consecutive three-drug regimens. Among these treatment strategies, initiating therapy with the three-drug regimen of zidovudine, lamivudine, and efavirenz is the optimal choice.Copyright 2003 Massachusetts Medical Society

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