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 350:1850-1861 April 29, 2004 Number 18 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited.

Methods This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine–lamivudine–abacavir, zidovudine–lamivudine plus efavirenz, and zidovudine–lamivudine–abacavir plus efavirenz.

REsults We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log₁₀ (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P<0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups.

Conclusions In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.

Source Information

From the Weill Medical College of Cornell University, New York (R.M.G., B.R.S.); the Statistical and Data Analysis Center, Harvard School of Public Health, Boston (H.J.R., S.L.); the University of Hawaii, Honolulu (C.M.S.); the University of Southern California Medical Center, Los Angeles (K.E.S.); Quest Diagnostics, Baltimore (W.A.M.); the University of Alabama at Birmingham, Birmingham (E.P.A.); the University of North Carolina at Chapel Hill, Chapel Hill (C.D.P.); Northwestern University, Chicago (R.L.M.); Ohio State University, Columbus (W.E.M.); the Harbor–UCLA Medical Center, Los Angeles (M.D.W.); the University of Rochester Medical Center, Rochester, N.Y. (R.C.R.); Social and Scientific Systems, Silver Spring, Md. (S.S.); the Division of AIDS, National Institute of Allergy and Infectious Disease, Bethesda, Md. (K.L.K.); and Brigham and Women's Hospital and Harvard Medical School, Boston (D.R.K.).

Address reprint requests to Dr. Gulick at the Cornell Clinical Trials Unit, Box 566, 525 E. 68th St., New York, NY 10021, or at rgulick{at}med.cornell.edu.

Full Text of this Article

Related Letters:

Triple-Nucleoside Regimens versus Efavirenz
De Luca A., Di Giambenedetto S., Maida I., Nuñez M., Soriano V., Gulick R. M., Ribaudo H., Kuritzkes D., the AIDS Clinical Trials Study Group A5095 Team
Extract | Full Text | PDF  
N Engl J Med 2004; 351:717-719, Aug 12, 2004. Correspondence

This article has been cited by other articles:

• Domingo, P., Suarez-Lozano, I., Torres, F., Teira, R., Lopez-Aldeguer, J., Vidal, F., Munoz, A., Viciana, P., Lozano, F., Vergara, A., Roca, B., Garcia Alcalde, M. L., Cosin, J., Terron, A., Galindo, M. J., Geijo, P., Ribera, E., Gonzalez, J., Sanchez, T., Lacalle, J. R., Garrido, M. (2008). First-line antiretroviral therapy with efavirenz or lopinavir/ritonavir plus two nucleoside analogues: the SUSKA study, a non-randomized comparison from the VACH cohort. J Antimicrob Chemother 61: 1348-1358 [Abstract] [Full Text]  
• Riddler, S. A., Haubrich, R., DiRienzo, A. G., Peeples, L., Powderly, W. G., Klingman, K. L., Garren, K. W., George, T., Rooney, J. F., Brizz, B., Lalloo, U. G., Murphy, R. L., Swindells, S., Havlir, D., Mellors, J. W., the AIDS Clinical Trials Group Study A5142 Team, (2008). Class-Sparing Regimens for Initial Treatment of HIV-1 Infection. NEJM 358: 2095-2106 [Abstract] [Full Text]  
• Garcia-Gasco, P., Maida, I., Blanco, F., Barreiro, P., Martin-Carbonero, L., Vispo, E., Gonzalez-Lahoz, J., Soriano, V. (2008). Episodes of low-level viral rebound in HIV-infected patients on antiretroviral therapy: frequency, predictors and outcome. J Antimicrob Chemother 61: 699-704 [Abstract] [Full Text]  
• Nicol, A F, Nuovo, G J, Salomao-Estevez, A, Grinsztein, B, Tristao, A, Russomano, F, Lapa e Silva, J R, Oliveira, M P, Pirmez, C (2008). Immune factors involved in the cervical immune response in the HIV/HPV co-infection. J. Clin. Pathol. 61: 84-88 [Abstract] [Full Text]  
• Go, R., Steigbigel, R. (2007). Interleukin 2 and HIV RNA Levels. Arch Intern Med 167: 2144-2145 [Full Text]  
• Ribaudo, H. J., Kuritzkes, D. R., Gulick, R. M. (2007). A Comparison of Three Initial Antiretroviral AIDS Regimens. NEJM 357: 1056-1057 [Full Text]  
• Cruchaga, C., Anso, E., Rouzaut, A., Martinez-Irujo, J. J. (2006). Selective Excision of Chain-terminating Nucleotides by HIV-1 Reverse Transcriptase with Phosphonoformate as Substrate. J. Biol. Chem. 281: 27744-27752 [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]  
• Hammer, S. M., Saag, M. S., Schechter, M., Montaner, J. S. G., Schooley, R. T., Jacobsen, D. M., Thompson, M. A., Carpenter, C. C. J., Fischl, M. A., Gazzard, B. G., Gatell, J. M., Hirsch, M. S., Katzenstein, D. A., Richman, D. D., Vella, S., Yeni, P. G., Volberding, P. A. (2006). Treatment for Adult HIV Infection: 2006 Recommendations of the International AIDS Society-USA Panel. JAMA 296: 827-843 [Abstract] [Full Text]  
• Deeks, S. G (2006). Antiretroviral treatment of HIV infected adults.. BMJ 332: 1489-1489 [Full Text]  
• Zuniga, J. M. (2006). State of HIV Treatment: Results of the International Association of Physicians in AIDS Care Surveys of HIV-Positive Patients and HIV-Treating Physicians in the United States. J Int Assoc Physicians AIDS Care (Chic Ill) 5: 51-56 [Abstract]  
• Parikh, U. M., Bacheler, L., Koontz, D., Mellors, J. W. (2006). The K65R Mutation in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Exhibits Bidirectional Phenotypic Antagonism with Thymidine Analog Mutations.. J. Virol. 80: 4971-4977 [Abstract] [Full Text]  
• Mocroft, A, Neaton, J, Bebchuk, J, Staszewski, S, Antunes, F, Knysz, B, Law, M, Phillips, A N, Lundgren, J D (2006). The feasibility of clinical endpoint trials in HIV infection in the highly active antiretroviral treatment (HAART) era. Clin Trials 3: 119-132 [Abstract]  
• Stebbing, J., Mazhar, D., Lewis, R., Palmieri, C., Hatzimichael, E., Nelson, M., Gazzard, B., Bower, M. (2006). The presentation and survival of patients with non-cutaneous AIDS-associated Kaposi's sarcoma. Ann Oncol 17: 503-506 [Abstract] [Full Text]  
• Severe, P., Leger, P., Charles, M., Noel, F., Bonhomme, G., Bois, G., George, E., Kenel-Pierre, S., Wright, P. F., Gulick, R., Johnson, W. D. Jr., Pape, J. W., Fitzgerald, D. W. (2005). Antiretroviral therapy in a thousand patients with AIDS in Haiti.. NEJM 353: 2325-2334 [Abstract] [Full Text]  
• Clifford, D. B., Evans, S., Yang, Y., Acosta, E. P., Goodkin, K., Tashima, K., Simpson, D., Dorfman, D., Ribaudo, H., Gulick, R. M., for the A5097s Study Team*, (2005). Impact of Efavirenz on Neuropsychological Performance and Symptoms in HIV-Infected Individuals. ANN INTERN MED 143: 714-721 [Abstract] [Full Text]  
• Hammer, S. M. (2005). Clinical practice. Management of newly diagnosed HIV infection.. NEJM 353: 1702-1710 [Full Text]  
• Delaunay, C., Brun-Vezinet, F., Landman, R., Collin, G., Peytavin, G., Trylesinski, A., Flandre, P., Miller, M., Descamps, D., the Tonus Trial Study Group, (2005). Comparative Selection of the K65R and M184V/I Mutations in Human Immunodeficiency Virus Type 1-Infected Patients Enrolled in a Trial of First-Line Triple-Nucleoside Analog Therapy (Tonus IMEA 021). J. Virol. 79: 9572-9578 [Abstract] [Full Text]  
• Stanic, A., Schneider, T. K. (2005). Overview of Antiretroviral Agents in 2005. Journal of Pharmacy Practice 18: 228-246 [Abstract]  
• Latham, V., Stebbing, J., Mandalia, S., Michailidis, C., Davies, E., Bower, M., Gazzard, B., Nelson, M. (2005). Adherence to trizivir and tenofovir as a simplified salvage regimen is associated with suppression of viraemia and a decreased cholesterol. J Antimicrob Chemother 56: 186-189 [Abstract] [Full Text]  
• Wainberg, M. A., Brenner, B. G., Turner, D. (2005). Changing Patterns in the Selection of Viral Mutations among Patients Receiving Nucleoside and Nucleotide Drug Combinations Directed against Human Immunodeficiency Virus Type 1 Reverse Transcriptase. Antimicrob. Agents Chemother. 49: 1671-1678 [Full Text]  
• Parikh, U. M., Koontz, D. L., Chu, C. K., Schinazi, R. F., Mellors, J. W. (2005). In Vitro Activity of Structurally Diverse Nucleoside Analogs against Human Immunodeficiency Virus Type 1 with the K65R Mutation in Reverse Transcriptase. Antimicrob. Agents Chemother. 49: 1139-1144 [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]  
• Maggon, K. (2004). Regulatory reforms and GCP clinical trials with new drugs in India. Clin Trials 1: 461-467 [Abstract]  
• (2004). Other articles noted. Evid. Based Med. 9: e5-e5 [Full Text]  
• Arribas, J. R. (2004). The rise and fall of triple nucleoside reverse transcriptase inhibitor (NRTI) regimens. J Antimicrob Chemother 54: 587-592 [Abstract] [Full Text]  
• De Luca, A., Di Giambenedetto, S., Maida, I., Nunez, M., Soriano, V., Gulick, R. M., Ribaudo, H., Kuritzkes, D., the AIDS Clinical Trials Study Group A5095 Team, (2004). Triple-Nucleoside Regimens versus Efavirenz. NEJM 351: 717-719 [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]  
• Shaefer, M. S (2004). Abacavir/Lamivudine/Zidovudine Continues to Be a Valid and Useful Antiretroviral Regimen. The Annals of Pharmacotherapy 38: 1314-1316 [Full Text]  
• (2004). ACTG 5095: Triple Nucleosides Redux. AIDS Clin Care 2004: 2-2 [Full Text]  
• (2004). Insights into Initial HIV Therapy. JWatch Infect. Diseases 2004: 2-2 [Full Text]  
• (2004). Alternatives to Protease Inhibitors for HIV Treatment. JWatch General 2004: 1-1 [Full Text]