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 349:1036-1046 September 11, 2003 Number 11 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material 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 We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved.

Methods We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter.

Results At 12 months, the Kaplan–Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups.

Conclusions When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.

Source Information

From the Hospital Clínic, Barcelona (E.M., J.A.A., A.C., E.L., J.M.G.); Hospital de Bellvitge, L'Hospitalet (D.P.); Hospital de Mútua de Terrassa, Terrassa (D.D.); Hospital de Vall d'Hebrón, Barcelona (E.R.); Hospital de la Santa Creu i Sant Pau, Barcelona (P.D.); Hospital del Mar, Barcelona (H.K.); Hospital Son Dureta, Palma de Mallorca (M.R.); Hospital General de Granollers, Granollers (E.P.); Hospital de Mataró, Mataró (L.F.); Hospital Sant Jaume, Calella (J.M.L.); Hospital Parc Taulí, Sabadell (F.S.); Hospital Joan XXIII–Universitat Rovira i Virgili, Tarragona (C.R.); Hospital Creu Roja, L'Hospitalet (C.C.); Hospital de Viladecans, Viladecans (M.J.); and Hospital de Terrassa, Terrassa (M.A.) — all in Spain.

Address reprint requests to Dr. Martinez at the Infectious Diseases Unit, Hospital Clinic–Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain, or at esteban{at}fundsoriano.es.

Full Text of this Article

Related Letters:

Substitution for Protease Inhibitors in HIV Therapy
Hirschel B., Mikhail E., Martínez E., de Lazzari E., Gatell J. M.
Extract | Full Text | PDF  
N Engl J Med 2003; 349:2460-2461, Dec 18, 2003. Correspondence

This article has been cited by other articles:

• Rotger, M., Bayard, C., Taffe, P., Martinez, R., Cavassini, M., Bernasconi, E., Battegay, M., Hirschel, B., Furrer, H., Witteck, A., Weber, R., Ledergerber, B., Telenti, A., Tarr, P. E., the Swiss HIV Cohort Study, (2009). Contribution of Genome-Wide Significant Single-Nucleotide Polymorphisms and Antiretroviral Therapy to Dyslipidemia in HIV-Infected Individuals: A Longitudinal Study. Circ Cardiovasc Genet 2: 621-628 [Abstract] [Full Text]  
• Maggiolo, F. (2009). Efavirenz: a decade of clinical experience in the treatment of HIV. J Antimicrob Chemother 64: 910-928 [Abstract] [Full Text]  
• Perez-Elias, M. J., Moreno, A., Casado, J. L., Dronda, F., Antela, A., Lopez, D., Quereda, C., Navas, E., Hermida, J. M., Del Sol, E., Moreno, S. (2009). Observational Study to Evaluate Clinical Outcomes After First-Line Efavirenz-or Lopinavir-Ritonavir-Based HAART in Treatment-Naive Patients. J Int Assoc Physicians AIDS Care (Chic Ill) 8: 308-313 [Abstract]  
• Gutierrez-Valencia, A., Viciana, P., Palacios, R., Ruiz-Valderas, R., Lozano, F., Terron, A., Rivero, A., Lopez-Cortes, L. F., for the Sociedad Andaluza de Enfermedades Infeccio, (2009). Stepped-Dose Versus Full-Dose Efavirenz for HIV Infection and Neuropsychiatric Adverse Events: A Randomized Trial. ANN INTERN MED 151: 149-156 [Abstract] [Full Text]  
• Girard, P.-M., Cabie, A., Michelet, C., Verdon, R., Katlama, C., Mercie, P., Morand-Joubert, L., Petour, P., Monchecourt, F., Chene, G., Trylesinski, A., on behalf of the COOL Study Team, (2009). A randomized trial of two-drug versus three-drug tenofovir-containing maintenance regimens in virologically controlled HIV-1 patients. J Antimicrob Chemother 64: 126-134 [Abstract] [Full Text]  
• Waters, L (2009). Considering the individual - principles of treatment choice. Int J STD AIDS 20: 2-6 [Abstract] [Full Text]  
• Rey, D., Hoen, B., Chavanet, P., Schmitt, M. P., Hoizey, G., Meyer, P., Peytavin, G., Spire, B., Allavena, C., Diemer, M., May, T., Schmit, J. L., Duong, M., Calvez, V., Lang, J. M. (2009). High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients. J Antimicrob Chemother 63: 380-388 [Abstract] [Full Text]  
• Puoti, M., Nasta, P., Gatti, F., Matti, A., Prestini, K., Biasi, L., Carosi, G. (2009). HIV-Related Liver Disease: ARV Drugs, Coinfection, and Other Risk Factors. J Int Assoc Physicians AIDS Care (Chic Ill) 8: 30-42 [Abstract]  
• Brown, T. T. (2008). Approach to the Human Immunodeficiency Virus-Infected Patient with Lipodystrophy. J. Clin. Endocrinol. Metab. 93: 2937-2945 [Abstract] [Full Text]  
• Perez-Molina, J. A., Domingo, P., Martinez, E., Moreno, S. (2008). The role of efavirenz compared with protease inhibitors in the body fat changes associated with highly active antiretroviral therapy. J Antimicrob Chemother 62: 234-245 [Abstract] [Full Text]  
• Wierzbicki, A. S, Purdon, S. D, Hardman, T. C, Kulasegaram, R., Peters, B. S (2008). Review: Clinical aspects of the management of HIV lipodystrophy. British Journal of Diabetes & Vascular Disease 8: 113-119 [Abstract]  
• Hakeem, L., Campbell, I. W, Bhattacharyya, D. N. (2008). HIV-associated lipodystrophy - a new metabolic syndrome. British Journal of Diabetes & Vascular Disease 8: 129-134 [Abstract]  
• Clotet, B. (2008). Once-daily dosing of nevirapine in HAART. J Antimicrob Chemother 61: 13-16 [Abstract] [Full Text]  
• Soriano, V., Garcia-Gasco, P., Vispo, E., Ruiz-Sancho, A., Blanco, F., Martin-Carbonero, L., Rodriguez-Novoa, S., Morello, J., de Mendoza, C., Rivas, P., Barreiro, P., Gonzalez-Lahoz, J. (2008). Efficacy and safety of replacing lopinavir with atazanavir in HIV-infected patients with undetectable plasma viraemia: final results of the SLOAT trial. J Antimicrob Chemother 61: 200-205 [Abstract] [Full Text]  
• Falutz, J., Allas, S., Blot, K., Potvin, D., Kotler, D., Somero, M., Berger, D., Brown, S., Richmond, G., Fessel, J., Turner, R., Grinspoon, S. (2007). Metabolic Effects of a Growth Hormone-Releasing Factor in Patients with HIV. NEJM 357: 2359-2370 [Abstract] [Full Text]  
• Rivero, A., Mira, J. A., Pineda, J. A. (2007). Liver toxicity induced by non-nucleoside reverse transcriptase inhibitors. J Antimicrob Chemother 59: 342-346 [Abstract] [Full Text]  
• Negredo, E., Bonjoch, A., Clotet, B. (2006). Benefits and concerns of simplification strategies in HIV-infected patients. J Antimicrob Chemother 58: 235-242 [Abstract] [Full Text]  
• Stebbing, J, Bower, M, Holmes, P, Gazzard, B, Nelson, M (2006). A single centre cohort experience with a new once daily antiretroviral drug.. Postgrad. Med. J. 82: 343-346 [Abstract] [Full Text]  
• Pulido, F., Ribera, E., Moreno, S., Munoz, A., Podzamczer, D., del Pozo, M. A., Rivero, A., Rodriguez, F., Sanjoaquin, I., Teira, R., Viciana, P., Villalonga, C., Antela, A., Carmena, J., Ena, J., Gonzalez, E., Kindelan, J. M., Mallolas, J., Marquez, M., Martinez, E. (2005). Once-daily antiretroviral therapy: Spanish Consensus Statement. J Antimicrob Chemother 56: 808-818 [Abstract] [Full Text]  
• Milinkovic, A., Martinez, E. (2005). Current perspectives on HIV-associated lipodystrophy syndrome. J Antimicrob Chemother 56: 6-9 [Abstract] [Full Text]  
• Maggiolo, F., Ripamonti, D., Suter, F. (2005). Switch strategies in patients on effective HAART. J Antimicrob Chemother 55: 821-823 [Abstract] [Full Text]  
• Duong, M., Buisson, M., Peytavin, G., Kohli, E., Piroth, L., Martha, B., Grappin, M., Chavanet, P., Portier, H. (2005). Low Trough Plasma Concentrations of Nevirapine Associated with Virologic Rebounds in HIV-Infected Patients Who Switched from Protease Inhibitors. The Annals of Pharmacotherapy 39: 603-609 [Abstract] [Full Text]  
• Grinspoon, S., Carr, A. (2005). Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults. NEJM 352: 48-62 [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]  
• Bucher, H. C., Young, J., Battegay, M. (2004). Protease inhibitor-sparing simplified maintenance therapy: a need for perspective. J Antimicrob Chemother 54: 303-305 [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]  
• 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]  
• 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]  
• Hadri, K. E., Glorian, M., Monsempes, C., Dieudonne, M.-N., Pecquery, R., Giudicelli, Y., Andreani, M., Dugail, I., Feve, B. (2004). In Vitro Suppression of the Lipogenic Pathway by the Nonnucleoside Reverse Transcriptase Inhibitor Efavirenz in 3T3 and Human Preadipocytes or Adipocytes. J. Biol. Chem. 279: 15130-15141 [Abstract] [Full Text]  
• Hirschel, B., Mikhail, E., Martinez, E., de Lazzari, E., Gatell, J. M. (2003). Substitution for Protease Inhibitors in HIV Therapy. NEJM 349: 2460-2461 [Full Text]  
• (2003). PI Substitution Strategies -- The Definitive Study (For Now). AIDS Clin Care 2003: 10-10 [Full Text]  
• (2003). Simplifying HIV Therapy: History Counts. JWatch Infect. Diseases 2003: 3-3 [Full Text]