Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine.
Author(s): Kempf DJ, King MS, Bernstein B, Cernohous P, Bauer E, Moseley J, Gu K, Hsu A, Brun S, Sun E
Affiliation(s): Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois, USA. dale.kempf@abbott.com
Publication date & source: 2004-01-01, J Infect Dis., 189(1):51-60. Epub 2003 Dec 31.
Publication type: Clinical Trial; Clinical Trial, Phase III; Multicenter Study; Randomized Controlled Trial
Study M98-863 was a double-blind, randomized, phase 3 study that compared lopinavir/ritonavir with nelfinavir, each coadministered with stavudine and lamivudine, in 653 antiretroviral therapy-naive human immunodeficiency virus (HIV) type 1-infected subjects. The incidence of HIV drug resistance was analyzed using baseline and rebound virus isolates from subjects with plasma HIV RNA >400 copies/mL from weeks 24 to 108 of therapy. No evidence of genotypic or phenotypic resistance to lopinavir/ritonavir, defined as any active site or primary mutation in HIV protease, was detected in virus isolates from 51 lopinavir/ritonavir-treated subjects with available genotypes. Primary mutations related to nelfinavir resistance (D30N and/or L90M) were observed in 43 (45%) of 96 nelfinavir-treated subjects. Resistance to lamivudine and stavudine was also significantly higher in nelfinavir-treated versus lopinavir/ritonavir-treated subjects. These differences suggest substantially different genetic and pharmacological barriers to resistance for these 2 protease inhibitors and may have implications for strategies for initiating antiretroviral therapy.
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