FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 349:2304-2315 December 11, 2003 Number 24 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Aragorn Editorial by Skolnik, P. R. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background It 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.

Methods In 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.

Results A 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).

Conclusions There 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.

Source Information

From Stanford University Medical Center, Stanford, Calif. (R.W.S., T.C.M.); the Harvard School of Public Health (L.M.S., V.D.G.) and Harvard Medical School (G.K.R., M.S.H.) — both in Boston; Social & Scientific Systems, Silver Spring, Md. (S.W.S.); the Vanderbilt University Medical Center, Nashville (R.T.D.); the Birmingham Veterans Affairs Medical Center and the University of Alabama at Birmingham School of Medicine, Birmingham (V.A.J.); the State University of New York, Buffalo (G.D.M.); the University of Texas Medical Branch, Galveston (M.A.N.); the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. (A.I.M.); Case Western Reserve University, Cleveland (B.M.G.); the University of Cincinnati College of Medicine, Cincinnati (P.K.); the University of California–San Diego, San Diego (R.H.); Bristol-Myers Squibb, Plainsboro, N.J. (M.S.); GlaxoSmithKline, Research Triangle Park, N.C. (S.D.M.); and the Istituto Superiore di Sanita, Rome (S.V.).

Address reprint requests to Dr. Robbins at Massachusetts General Hospital, Infectious Disease Unit, 55 Fruit St., Boston, MA 02114, or at grobbins{at}partners.org.

Full Text of this Article

This article has been cited by other articles:

• Bendavid, E., Young, S. D., Katzenstein, D. A., Bayoumi, A. M., Sanders, G. D., Owens, D. K. (2008). Cost-effectiveness of HIV Monitoring Strategies in Resource-Limited Settings: A Southern African Analysis. Arch Intern Med 168: 1910-1918 [Abstract] [Full Text]  
• Gulick, R. M., Ribaudo, H. J., Shikuma, C. M., Lalama, C., Schackman, B. R., Meyer, W. A. III, Acosta, E. P., Schouten, J., Squires, K. E., Pilcher, C. D., Murphy, R. L., Koletar, S. L., Carlson, M., Reichman, R. C., Bastow, B., Klingman, K. L., Kuritzkes, D. R., for the AIDS Clinical Trials Group (ACTG) A5095 St, (2006). Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial.. JAMA 296: 769-781 [Abstract] [Full Text]  
• Vingerhoets, J., Azijn, H., Fransen, E., De Baere, I., Smeulders, L., Jochmans, D., Andries, K., Pauwels, R., de Bethune, M.-P. (2005). TMC125 Displays a High Genetic Barrier to the Development of Resistance: Evidence from In Vitro Selection Experiments. J. Virol. 79: 12773-12782 [Abstract] [Full Text]  
• Smith, P. F., Robbins, G. K., Shafer, R. W., Wu, H., Yu, S., Hirsch, M. S., Merigan, T. C., Park, J.-G., Forrest, A., Fischl, M. A., Morse, G. D., the ACTG 384-5006 Team, (2005). Pharmacokinetics of Nelfinavir and Efavirenz in Antiretroviral-Naive, Human Immunodeficiency Virus-Infected Subjects when Administered Alone or in Combination with Nucleoside Analog Reverse Transcriptase Inhibitors. Antimicrob. Agents Chemother. 49: 3558-3561 [Abstract] [Full Text]  
• Torti, C., Maggiolo, F., Patroni, A., Suter, F., Ladisa, N., Paraninfo, G., Pierotti, P., Orani, A. M., Minoli, L., Arici, C., Sighinolfi, L., Tinelli, C., Carosi, G., for the MASTER Cohort, (2005). Exploratory analysis for the evaluation of lopinavir/ritonavir-versus efavirenz-based HAART regimens in antiretroviral-naive HIV-positive patients: results from the Italian MASTER Cohort. J Antimicrob Chemother 56: 190-195 [Abstract] [Full Text]  
• Orkin, C., Stebbing, J., Nelson, M., Bower, M., Johnson, M., Mandalia, S., Jones, R., Moyle, G., Fisher, M., Gazzard, B. (2005). A randomized study comparing a three- and four-drug HAART regimen in first-line therapy (QUAD study). J Antimicrob Chemother 55: 246-251 [Abstract] [Full Text]  
• Post, F. A., Easterbrook, P. J. (2005). Antiretroviral Therapy in Advanced HIV-1 Infection. J Int Assoc Physicians AIDS Care (Chic Ill) 4: 8-15 [Abstract]  
• Greenberg, M. L., Cammack, N. (2004). Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 54: 333-340 [Abstract] [Full Text]  
• Yeni, P. G., Hammer, S. M., Hirsch, M. S., Saag, M. S., Schechter, M., Carpenter, C. C. J., Fischl, M. A., Gatell, J. M., Gazzard, B. G., Jacobsen, D. M., Katzenstein, D. A., Montaner, J. S. G., Richman, D. D., Schooley, R. T., Thompson, M. A., Vella, S., Volberding, P. A. (2004). Treatment for Adult HIV Infection: 2004 Recommendations of the International AIDS Society-USA Panel. JAMA 292: 251-265 [Abstract] [Full Text]  
• Clay, P. G (2004). Single-Class Therapy for HIV Is Not Optimal Care. The Annals of Pharmacotherapy 38: 1307-1309 [Full Text]  
• Stebbing, J., Gazzard, B., Mandalia, S., Teague, A., Waterston, A., Marvin, V., Nelson, M., Bower, M. (2004). Antiretroviral Treatment Regimens and Immune Parameters in the Prevention of Systemic AIDS-Related Non-Hodgkin's Lymphoma. JCO 22: 2177-2183 [Abstract] [Full Text]  
• (2004). AZT/3TC/Efavirenz Is a Good Choice for Initial HIV Treatment. JWatch General 2004: 3-3 [Full Text]  
• (2004). Refining the Choices for Initial HIV Therapy. JWatch Infect. Diseases 2004: 4-4 [Full Text]  
• (2004). ACTG 384 -- Complicated, but Worth the Work. AIDS Clin Care 2004: 1-1 [Full Text]  
• Robbins, G. K., De Gruttola, V., Shafer, R. W., Smeaton, L. M., Snyder, S. W., Pettinelli, C., Dube, M. P., Fischl, M. A., Pollard, R. B., Delapenha, R., Gedeon, L., van der Horst, C., Murphy, R. L., Becker, M. I., D'Aquila, R. T., Vella, S., Merigan, T. C., Hirsch, M. S., the AIDS Clinical Trials Group 384 Team, (2003). Comparison of Sequential Three-Drug Regimens as Initial Therapy for HIV-1 Infection. NEJM 349: 2293-2303 [Abstract] [Full Text]  
• Skolnik, P. R. (2003). HIV Therapy -- What Do We Know, and When Do We Know It?. NEJM 349: 2351-2352 [Full Text]