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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.

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