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 346:2039-2046 June 27, 2002 Number 26 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Hammer, S. M. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Lopinavir is a newly developed inhibitor of human immunodeficiency virus (HIV) protease that, when formulated with ritonavir, yields mean trough plasma lopinavir concentrations that are at least 75 times as high as that needed to inhibit replication of wild-type HIV by 50 percent.

Methods We conducted a double-blind trial in which 653 HIV-infected adults who had not received antiretroviral therapy for more than 14 days were randomly assigned to receive either lopinavir–ritonavir (400 mg of lopinavir plus 100 mg of ritonavir twice daily) with nelfinavir placebo or nelfinavir (750 mg three times daily) with lopinavir–ritonavir placebo. All patients also received open-label stavudine and lamivudine. The primary efficacy end points were the presence of fewer than 400 HIV RNA copies per milliliter of plasma at week 24 and the time to the loss of virologic response through week 48.

Results At week 48, greater proportions of patients treated with lopinavir–ritonavir than of patients treated with nelfinavir had fewer than 400 copies of HIV RNA per milliliter (75 percent vs. 63 percent, P<0.001) and fewer than 50 copies per milliliter (67 percent vs. 52 percent, P<0.001). The time to the loss of virologic response was greater in the lopinavir–ritonavir group than in the nelfinavir group (hazard ratio, 2.0; 95 percent confidence interval, 1.5 to 2.7; P<0.001). The estimated proportion of patients with a persistent virologic response through week 48 was 84 percent for patients receiving lopinavir–ritonavir and 66 percent for those receiving nelfinavir. Both regimens were well tolerated, with the rate of discontinuation related to the study drugs at 3.4 percent among patients receiving lopinavir–ritonavir and 3.7 percent among patients receiving nelfinavir. Among patients with more than 400 copies of HIV RNA per milliliter at some point from week 24 through week 48, resistance mutations in HIV protease were demonstrated in viral isolates from 25 of 76 nelfinavir-treated patients (33 percent) and none of 37 patients treated with lopinavir–ritonavir (P<0.001).

Conclusions For the initial treatment of HIV-infected adults, a combination regimen that includes lopinavir–ritonavir is well tolerated and has antiviral activity superior to that of a nelfinavir-containing regimen.

Source Information

From Toronto Hospital, University Health Network, University of Toronto, Toronto (S.W.); Abbott Laboratories, Abbott Park, Ill. (B.B., M.K., A.J., S.B., E.S.); Servico VIH–Medicina Interna II, Hopital Universitario La Paz, Madrid (J.A.); Harbor UCLA Medical Center, Torrance, Calif. (G.B.); Tower Infectious Diseases, Los Angeles (P.R.); Royal Free Hospital, London (M.J.); Johannesburg, South Africa (D.J.); and Montreal Chest Institute, Royal Victoria Hospital, Montreal (R.L.).

Address reprint requests to Dr. Walmsley at Toronto General Hospital, Division of Infectious Diseases, Rm. EN G-219, 200 Elizabeth St., Toronto, ON M5G 2C4, Canada, or at sharon.walmsley{at}uhn.on.ca.

Full Text of this Article

This article has been cited by other articles:

• Calza, L, Manfredi, R, Pocaterra, D, Chiodo, F (2008). Efficacy and tolerability of a fosamprenavir-ritonavir-based versus a lopinavir-ritonavir-based antiretroviral treatment in 82 therapy-nayive patients with HIV-1 infection. Int J STD AIDS 19: 541-544 [Abstract] [Full Text]  
• 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]  
• Torpey, K., Kasonde, D., Goma, F. (2008). The experience of patients taking the lopinavir/ritonavir (LPV/r) tablet compared with the LPV/r soft-gel capsule in Zambia. Int J STD AIDS 19: 1-4 [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]  
• Dekhtyar, T., Ng, T. I., Lu, L., Masse, S., DeGoey, D. A., Flosi, W. J., Grampovnik, D. J., Klein, L. L., Kempf, D. J., Molla, A. (2008). Characterization of a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor, A-790742. Antimicrob. Agents Chemother. 52: 1337-1344 [Abstract] [Full Text]  
• Palmer, S., Maldarelli, F., Wiegand, A., Bernstein, B., Hanna, G. J., Brun, S. C., Kempf, D. J., Mellors, J. W., Coffin, J. M., King, M. S. (2008). Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc. Natl. Acad. Sci. USA 105: 3879-3884 [Abstract] [Full Text]  
• Burgoyne, R. W., Tan, D. H. S. (2008). Prolongation and quality of life for HIV-infected adults treated with highly active antiretroviral therapy (HAART): a balancing act. J Antimicrob Chemother 61: 469-473 [Abstract] [Full Text]  
• Hodder, S. (2008). Know Your Patient: What Conditions Affect Initial HIV Treatment Success?. J Int Assoc Physicians AIDS Care (Chic Ill) 7: S5-S9 [Abstract]  
• Youle, M. (2007). Overview of boosted protease inhibitors in treatment-experienced HIV-infected patients. J Antimicrob Chemother 60: 1195-1205 [Abstract] [Full Text]  
• Ofotokun, I., Chuck, S. K., Binongo, J. N., Palau, M., Lennox, J. L., Acosta, E. P. (2007). Lopinavir/Ritonavir Pharmacokinetic Profile: Impact of Sex and Other Covariates Following a Change From Twice-Daily to Once-Daily Therapy. J Clin Pharmacol 47: 970-977 [Abstract] [Full Text]  
• Cameron, D. W., Becker, S., King, M. S., da Silva, B., Klein, C., Tokimoto, D., Foit, C., Calhoun, D., Bernstein, B., Hanna, G. J. (2007). Exploratory study comparing the metabolic toxicities of a lopinavir/ritonavir plus saquinavir dual protease inhibitor regimen versus a lopinavir/ritonavir plus zidovudine/lamivudine nucleoside regimen. J Antimicrob Chemother 59: 957-963 [Abstract] [Full Text]  
• Fulco, P. P., Vora, U. B, Bearman, G. M. (2006). Acid Suppressive Therapy and the Effects on Protease Inhibitors. The Annals of Pharmacotherapy 40: 1974-1983 [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]  
• Carosi, G., Torti, C., Andreoni, M., Angarano, G., Antinori, A., Bonora, S., Borderi, M., Castagna, A., Castelli, F., Cauda, R., Chiodo, F., D'arminio-Monforte, A., De Luca, A., Di Perri, G., Dianzani, F., Filice, G., Galli, M., Lazzarin, A., Maggiolo, F., Maserati, R., Mazzotta, F., Moroni, M., Perno, C. F., Vullo, V., on behalf of the Members of the Italian HIV Guidel, (2006). Key questions in antiretroviral therapy: Italian Consensus Workshop (2005). J Antimicrob Chemother 57: 1055-1064 [Abstract] [Full Text]  
• Peng, J. Z., Pulido, F., Causemaker, S. J. K., Li, J., Lorenzo, A., Cepeda, C., Cabanillas, J. A. G., DaSilva, B., Brun, S. C., Arribas, J. (2006). Pharmacokinetics of Lopinavir/Ritonavir in HIV/Hepatitis C Virus-Coinfected Subjects With Hepatic Impairment.. J Clin Pharmacol 46: 265-274 [Abstract] [Full Text]  
• Khouli, H., Afrasiabi, A., Shibli, M., Hajal, R., Barrett, C. R., Homel, P. (2005). Outcome of Critically Ill Human Immunodeficiency Virus-Infected Patients in the Era of Highly Active Antiretroviral Therapy. J Intensive Care Med 20: 279-285 [Abstract]  
• 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]  
• Hammer, S. M. (2005). Clinical practice. Management of newly diagnosed HIV infection.. NEJM 353: 1702-1710 [Full Text]  
• Seminari, E., Gentilini, G., Galli, L., Hasson, H., Danise, A., Carini, E., Dorigatti, F., Soldarini, A., Lazzarin, A., Castagna, A. (2005). Higher plasma lopinavir concentrations are associated with a moderate rise in cholestasis markers in HIV-infected patients. J Antimicrob Chemother 56: 790-792 [Abstract] [Full Text]  
• Kaplan, S. S., Hicks, C. B. (2005). Safety and antiviral activity of lopinavir/ritonavir-based therapy in human immunodeficiency virus type 1 (HIV-1) infection. J Antimicrob Chemother 56: 273-276 [Abstract] [Full Text]  
• Winston, A., Boffito, M. (2005). The management of HIV-1 protease inhibitor pharmacokinetic interactions. J Antimicrob Chemother 56: 1-5 [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]  
• Bongiovanni, M., Chiesa, E., Di Biagio, A., Meraviglia, P., Capetti, A., Tordato, F., Cicconi, P., Biasi, P., Bini, T., d'Arminio Monforte, A. (2005). Use of lopinavir/ritonavir in HIV-infected patients failing a first-line protease-inhibitor-containing HAART. J Antimicrob Chemother 55: 1003-1007 [Abstract] [Full Text]  
• Montes, M. L., Pulido, F., Barros, C., Condes, E., Rubio, R., Cepeda, C., Dronda, F., Antela, A., Sanz, J., Navas, E., Miralles, P., Berenguer, J., Perez, S., Zapata, A., Gonzalez-Garcia, J. J., Pena, J. M., Vazquez, J. J., Arribas, J. R. (2005). Lipid disorders in antiretroviral-naive patients treated with lopinavir/ritonavir-based HAART: frequency, characterization and risk factors. J Antimicrob Chemother 55: 800-804 [Abstract] [Full Text]  
• Scott, J. D. (2005). Simplifying the treatment of HIV infection with ritonavir-boosted protease inhibitors in antiretroviral-experienced patients. Am J Health Syst Pharm 62: 809-815 [Abstract] [Full Text]  
• Mo, H., King, M. S., King, K., Molla, A., Brun, S., Kempf, D. J. (2005). Selection of Resistance in Protease Inhibitor-Experienced, Human Immunodeficiency Virus Type 1-Infected Subjects Failing Lopinavir- and Ritonavir-Based Therapy: Mutation Patterns and Baseline Correlates. J. Virol. 79: 3329-3338 [Abstract] [Full Text]  
• Jerico, C., Knobel, H., Montero, M., Ordonez-Llanos, J., Guelar, A., Gimeno, J. L., Saballs, P., Lopez-Colomes, J. L., Pedro-Botet, J. (2005). Metabolic Syndrome Among HIV-Infected Patients: Prevalence, characteristics, and related factors. Diabetes Care 28: 132-137 [Abstract] [Full Text]  
• Waters, L., Stebbing, J., Jones, R., Michailidis, C., Sawleshwarkar, S., Mandalia, S., Bower, M., Nelson, M., Gazzard, B. (2004). A comparison of the CD4 response to antiretroviral regimens in patients commencing therapy with low CD4 counts. J Antimicrob Chemother 54: 503-507 [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]  
• Bangsberg, D. R., Moss, A. R., Deeks, S. G. (2004). Paradoxes of adherence and drug resistance to HIV antiretroviral therapy. J Antimicrob Chemother 53: 696-699 [Abstract] [Full Text]  
• Kinloch-de Loes, S. (2004). Role of therapeutic vaccines in the control of HIV-1. J Antimicrob Chemother 53: 562-566 [Abstract] [Full Text]  
• Clotet, B., Skolnik, P. R. (2004). Comparison of Regimens as Initial Therapy for HIV. NEJM 350: 1053-1054 [Full Text]  
• Furfine, E. S., Baker, C. T., Hale, M. R., Reynolds, D. J., Salisbury, J. A., Searle, A. D., Studenberg, S. D., Todd, D., Tung, R. D., Spaltenstein, A. (2004). Preclinical Pharmacology and Pharmacokinetics of GW433908, a Water-Soluble Prodrug of the Human Immunodeficiency Virus Protease Inhibitor Amprenavir. Antimicrob. Agents Chemother. 48: 791-798 [Abstract] [Full Text]  
• Yazdanpanah, Y., Sissoko, D., Egger, M., Mouton, Y., Zwahlen, M., Chene, G. (2004). Clinical efficacy of antiretroviral combination therapy based on protease inhibitors or non-nucleoside analogue reverse transcriptase inhibitors: indirect comparison of controlled trials. BMJ 328: 249- [Abstract] [Full Text]  
• Zeldin, R. K., Petruschke, R. A. (2004). Pharmacological and therapeutic properties of ritonavir-boosted protease inhibitor therapy in HIV-infected patients. J Antimicrob Chemother 53: 4-9 [Abstract] [Full Text]  
• Turner, D., Brenner, B., Wainberg, M. A. (2004). Relationships among various nucleoside resistance-conferring mutations in the reverse transcriptase of HIV-1. J Antimicrob Chemother 53: 53-57 [Abstract] [Full Text]  
• Saag, M. (2003). Is It Time To Proactively Switch Successful Antiretroviral Therapy? Carefully Check Your SWATCH. ANN INTERN MED 139: 148-149 [Full Text]  
• Pulido, F., Arribas, J. R. (2003). Treatment of advanced HIV infection. J Antimicrob Chemother 51: 225-227 [Full Text]  
• (2002). Lopinavir/Ritonavir vs. Nelfinavir in Treatment-Naive Patients. AIDS Clin Care 2002: 3-3 [Full Text]  
• (2002). Lopinavir-Ritonavir Eclipses Nelfinavir's Antiretroviral Potency. JWatch Infect. Diseases 2002: 4-4 [Full Text]