Class-Sparing Regimens for Initial Treatment of HIV-1 Infection
Sharon A. Riddler, M.D., M.P.H., Richard Haubrich, M.D., A. Gregory DiRienzo, Ph.D., Lynne Peeples, M.S., William G. Powderly, M.D., Karin L. Klingman, M.D., Kevin W. Garren, Ph.D., Tania George, Pharm.D., James F. Rooney, M.D., Barbara Brizz, M.H.S.Ed., B.S.N., Umesh G. Lalloo, M.D., Robert L. Murphy, M.D., Susan Swindells, M.B., B.S., Diane Havlir, M.D., John W. Mellors, M.D., for the AIDS Clinical Trials Group Study A5142 Team
Background The use of either efavirenz or lopinavir–ritonavirplus two nucleoside reverse-transcriptase inhibitors (NRTIs)is recommended for initial therapy for patients with human immunodeficiencyvirus type 1 (HIV-1) infection, but which of the two regimenshas greater efficacy is not known. The alternative regimen oflopinavir–ritonavir plus efavirenz may prevent toxic effectsassociated with NRTIs.
Methods In an open-label study, we compared three regimens forinitial therapy: efavirenz plus two NRTIs (efavirenz group),lopinavir–ritonavir plus two NRTIs (lopinavir–ritonavirgroup), and lopinavir–ritonavir plus efavirenz (NRTI-sparinggroup). We randomly assigned 757 patients with a median CD4count of 191 cells per cubic millimeter and a median HIV-1 RNAlevel of 4.8 log10 copies per milliliter to the three groups.
Results At a median follow-up of 112 weeks, the time to virologicfailure was longer in the efavirenz group than in the lopinavir–ritonavirgroup (P=0.006) but was not significantly different in the NRTI-sparinggroup from the time in either of the other two groups. At week96, the proportion of patients with fewer than 50 copies ofplasma HIV-1 RNA per milliliter was 89% in the efavirenz group,77% in the lopinavir–ritonavir group, and 83% in the NRTI-sparinggroup (P=0.003 for the comparison between the efavirenz groupand the lopinavir–ritonavir group). The groups did notdiffer significantly in the time to discontinuation becauseof toxic effects. At virologic failure, antiretroviral resistancemutations were more frequent in the NRTI-sparing group thanin the other two groups.
Conclusions Virologic failure was less likely in the efavirenzgroup than in the lopinavir–ritonavir group. The virologicefficacy of the NRTI-sparing regimen was similar to that ofthe efavirenz regimen but was more likely to be associated withdrug resistance. (ClinicalTrials.gov number, NCT00050895
[ClinicalTrials.gov]
.)
Source Information
From the University of Pittsburgh, Pittsburgh (S.A.R., J.W.M.); the University of California, San Diego, San Diego (R.H.); the Harvard School of Public Health, Boston (A.G.D., L.P.); University College Dublin, Dublin (W.G.P.); the Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD (K.L.K.); Abbott Laboratories, Abbott Park, IL (K.W.G.); Bristol-Myers Squibb, Plainsboro, NJ (T.G.); Gilead Sciences, Foster City, CA (J.F.R.); Social and Scientific Systems, Silver Spring, MD (B.B.); the University of KwaZulu Natal, Durban, South Africa (U.G.L.); Northwestern University, Chicago (R.L.M.); the University of Nebraska Medical Center, Omaha (S.S.); and the University of California, San Francisco, San Francisco (D.H.). Drs. Riddler and Haubrich contributed equally to this article. Ms. Brizz is deceased.
Address reprint requests to Dr. Riddler at 613 Falk Bldg., 3601 Fifth Ave., Pittsburgh, PA 15213, or at riddler{at}dom.pitt.edu.
Initial Treatment of HIV-1 Infection
Schulz T. R., Street A. C., Nicastri E., Narciso P., Andreoni M., Riddler S. A., Haubrich R., Mellors J. W.
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N Engl J Med 2008;
359:970-971, Aug 28, 2008.
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