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 339:1269-1276 October 29, 1998 Number 18 Next

	Full Text PDF Editorial by Cooper, D. A. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background The long-term effectiveness of potent three-drug antiretroviral regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection is limited by problems related to compliance and tolerability. We investigated whether two-drug maintenance therapy would suppress viral replication after a three-month period of aggressive triple-drug induction therapy.

Methods A total of 378 HIV-1–infected adults who had not received previous antiretroviral treatment received three months of induction therapy consisting of 300 mg of zidovudine every 12 hours, 150 mg of lamivudine every 12 hours, and 800 mg of indinavir every 8 hours. The 279 patients in whom the plasma HIV-1 RNA titer fell below 500 copies per milliliter after two months of triple-drug therapy, and who completed the induction phase, were randomly assigned at month 3 to one of the following three open-label maintenance regimens: zidovudine, lamivudine, and indinavir; zidovudine and lamivudine; or zidovudine and indinavir. The primary end point was an increase in HIV-1 RNA levels to 500 copies or more per milliliter during the maintenance phase.

Results The proportion of patients who reached the primary end point was significantly higher among patients receiving zidovudine plus lamivudine (29 of 93 patients, P<0.001) or zidovudine plus indinavir (21 of 94, P=0.01) than among patients receiving continued triple-drug therapy (8 of 92). This higher failure rate in the groups treated with the two-drug maintenance regimens was also observed in the subgroup of patients with maximally suppressed HIV-1 RNA (below 50 copies per milliliter) at the time of randomization to maintenance therapy.

Conclusions In HIV-1–infected adults not previously treated with antiretroviral drugs whose plasma HIV-1 RNA levels fell below 500 copies per milliliter after three months of induction therapy with zidovudine, lamivudine, and indinavir, two-drug maintenance therapy was less effective in sustaining a reduced viral load than continued three-drug therapy.

Source Information

From the Hôpital de l'Institut Pasteur and Assistance Publique–Hôpitaux de Paris, Paris (G.P.); Hôpital de l'Hôtel Dieu, Nantes (F.R.); Hôpital Bichat–Claude Bernard, Paris (F.B.-V., P.Y.); INSERM Service Commun 10, Villejuif (V.M., P.F., J.-P.A.); Paoli Calmettes Institut and Hôpital Sainte Marguerite, Marseilles (J.-A.G.); Hôpital de l'Archet, Nice (P.D.); and Hôpital Bicêtre, Le Kremlin Bicêtre (J.-F.D.) — all in France.

Address reprint requests to Dr. Pialoux at the Service des Maladies Infectieuses, Hôpital Rothschild, 33 Blvd. de Picpus, 75012 Paris, France.

Full Text of this Article

This article has been cited by other articles:

• Sanders, G. D., Bayoumi, A. M., Holodniy, M., Owens, D. K. (2008). Cost-Effectiveness of HIV Screening in Patients Older than 55 Years of Age. ANN INTERN MED 148: 889-903 [Abstract] [Full Text]  
• Swindells, S., DiRienzo, A. G., Wilkin, T., Fletcher, C. V., Margolis, D. M., Thal, G. D., Godfrey, C., Bastow, B., Ray, M. G., Wang, H., Coombs, R. W., McKinnon, J., Mellors, J. W., for the AIDS Clinical Trials Group 5201 Study Team, (2006). Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression.. JAMA 296: 806-814 [Abstract] [Full Text]  
• Sanders, G. D., Bayoumi, A. M., Sundaram, V., Bilir, S. P., Neukermans, C. P., Rydzak, C. E., Douglass, L. R., Lazzeroni, L. C., Holodniy, M., Owens, D. K. (2005). Cost-Effectiveness of Screening for HIV in the Era of Highly Active Antiretroviral Therapy. NEJM 352: 570-585 [Abstract] [Full Text]  
• Van Herrewege, Y., Vanham, G., Michiels, J., Fransen, K., Kestens, L., Andries, K., Janssen, P., Lewi, P. (2004). A Series of Diaryltriazines and Diarylpyrimidines Are Highly Potent Nonnucleoside Reverse Transcriptase Inhibitors with Possible Applications as Microbicides. Antimicrob. Agents Chemother. 48: 3684-3689 [Abstract] [Full Text]  
• Martinez, E., Arnaiz, J. A., Podzamczer, D., Dalmau, D., Ribera, E., Domingo, P., Knobel, H., Riera, M., Pedrol, E., Force, L., Llibre, J. M., Segura, F., Richart, C., Cortes, C., Javaloyas, M., Aranda, M., Cruceta, A., de Lazzari, E., Gatell, J. M., the Nevirapine, Efavirenz, and Abacavir (NEFA) Stu, (2003). Substitution of Nevirapine, Efavirenz, or Abacavir for Protease Inhibitors in Patients with Human Immunodeficiency Virus Infection. NEJM 349: 1036-1046 [Abstract] [Full Text]  
• Martinez-Picado, J., Negredo, E., Ruiz, L., Shintani, A., Fumaz, C. R., Zala, C., Domingo, P., Vilaro, J., Llibre, J. M., Viciana, P., Hertogs, K., Boucher, C., D'Aquila, R. T., Clotet, B., the SWATCH Study Team*, (2003). Alternation of Antiretroviral Drug Regimens for HIV Infection: A Randomized, Controlled Trial. ANN INTERN MED 139: 81-89 [Abstract] [Full Text]  
• Trabattoni, D., Lo Caputo, S., Biasin, M., Seminari, E., Di Pietro, M., Ravasi, G., Mazzotta, F., Maserati, R., Clerici, M. (2002). Modulation of Human Immunodeficiency Virus (HIV)-Specific Immune Response by Using Efavirenz, Nelfinavir, and Stavudine in a Rescue Therapy Regimen for HIV-Infected, Drug-Experienced Patients. CVI 9: 1114-1118 [Abstract] [Full Text]  
• Yeni, P. G., Hammer, S. M., Carpenter, C. C. J., Cooper, D. A., Fischl, M. A., Gatell, J. M., Gazzard, B. G., Hirsch, M. S., Jacobsen, D. M., Katzenstein, D. A., Montaner, J. S. G., Richman, D. D., Saag, M. S., Schechter, M., Schooley, R. T., Thompson, M. A., Vella, S., Volberding, P. A. (2002). Antiretroviral Treatment for Adult HIV Infection in 2002: Updated Recommendations of the International AIDS Society-USA Panel. JAMA 288: 222-235 [Abstract] [Full Text]  
• Havlir, D. V. (2002). Structured intermittent treatment for HIV disease: Necessary concession or premature compromise?. Proc. Natl. Acad. Sci. USA 99: 4-6 [Full Text]  
• Tedeschi, R., Enbom, M., Bidoli, E., Linde, A., De Paoli, P., Dillner, J. (2001). Viral Load of Human Herpesvirus 8 in Peripheral Blood of Human Immunodeficiency Virus-Infected Patients with Kaposi's Sarcoma. J. Clin. Microbiol. 39: 4269-4273 [Abstract] [Full Text]  
• Havlir, D. V., Bassett, R., Levitan, D., Gilbert, P., Tebas, P., Collier, A. C., Hirsch, M. S., Ignacio, C., Condra, J., Gunthard, H. F., Richman, D. D., Wong, J. K. (2001). Prevalence and Predictive Value of Intermittent Viremia With Combination HIV Therapy. JAMA 286: 171-179 [Abstract] [Full Text]  
• Savès, M., Raffi, F., Clevenbergh, P., Marchou, B., Waldner-Combernoux, A., Morlat, P., Le Moing, V., Rivière, C., Chêne, G., Leport, C., The APROCO Study Group, (2000). Hepatitis B or Hepatitis C Virus Infection Is a Risk Factor for Severe Hepatic Cytolysis after Initiation of a Protease Inhibitor-Containing Antiretroviral Regimen in Human Immunodeficiency Virus-Infected Patients. Antimicrob. Agents Chemother. 44: 3451-3455 [Abstract] [Full Text]  
• Nieuwkerk, P. T., Reijers, M. H. E., Weigel, H. M., Lange, J. M. A., Sprangers, M. A. G. (2000). Quality of Life in Maintenance vs Prolonged Induction Therapy for HIV. JAMA 284: 178-179 [Full Text]  
• Mouroux, M., Yvon-Groussin, A., Peytavin, G., Delaugerre, C., Legrand, M., Bossi, P., Do, B., Trylesinski, A., Diquet, B., Dohin, E., Delfraissy, J. F., Katlama, C., Calvez, V., The MIKADO Study Group, (2000). Early Virological Failure in Naive Human Immunodeficiency Virus Patients Receiving Saquinavir (Soft Gel Capsule)-Stavudine-Zalcitabine (MIKADO Trial) Is Not Associated with Mutations Conferring Viral Resistance. J. Clin. Microbiol. 38: 2726-2730 [Abstract] [Full Text]  
• Fleury, S., Rizzardi, G. P., Chapuis, A., Tambussi, G., Knabenhans, C., Simeoni, E., Meuwly, J.-Y., Corpataux, J.-M., Lazzarin, A., Miedema, F., Pantaleo, G. (2000). Long-term kinetics of T cell production in HIV-infected subjects treated with highly active antiretroviral therapy. Proc. Natl. Acad. Sci. USA 97: 5393-5398 [Abstract] [Full Text]  
• Markowitz, M. (2000). Resistance, Fitness, Adherence, and Potency: Mapping the Paths to Virologic Failure. JAMA 283: 250-251 [Full Text]  
• Davey, R. T. Jr., Bhat, N., Yoder, C., Chun, T.-W., Metcalf, J. A., Dewar, R., Natarajan, V., Lempicki, R. A., Adelsberger, J. W., Miller, K. D., Kovacs, J. A., Polis, M. A., Walker, R. E., Falloon, J., Masur, H., Gee, D., Baseler, M., Dimitrov, D. S., Fauci, A. S., Lane, H. C. (1999). HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc. Natl. Acad. Sci. USA 96: 15109-15114 [Abstract] [Full Text]  
• Muto, N. F., Martinand-Mari, C., Adelson, M. E., Suhadolnik, R. J. (1999). Inhibition of Replication of Reactivated Human Immunodeficiency Virus Type 1 (HIV-1) in Latently Infected U1 Cells Transduced with an HIV-1 Long Terminal Repeat-Driven PKR cDNA Construct. J. Virol. 73: 9021-9028 [Abstract] [Full Text]  
• Montaner, J. S. G. (1999). Induction/Maintenance Treatment Regimens for HIV. JAMA 281: 1680-1682 [Full Text]  
• Mayers, D. (1999). Maintenance Antiretroviral Treatment in HIV Infection. JAMA 281: 497-498 [Full Text]  
• Steinbrook, R. (1998). Caring for People with Human Immunodeficiency Virus Infection. NEJM 339: 1926-1928 [Full Text]  
• (1998). Induction Then Maintenance Therapy Ineffective for HIV Infection. JWatch Infect. Diseases 1998: 1-1 [Full Text]  
• (1998). Induction and Maintenance Strategy for Antiretroviral Therapy. AIDS Clin Care 1998: 3-3 [Full Text]  
• (1998). Antiretroviral Cocktails Can't Be Diluted. JWatch General 1998: 1-1 [Full Text]  
• Cooper, D. A., Emery, S. (1998). Therapeutic Strategies for HIV Infection -- Time to Think Hard. NEJM 339: 1319-1321 [Full Text]