title: Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine.
abstract: 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.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois, USA. dale.kempf@abbott.com
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Kempf
authors.forename: Martin S
authors.initials: MS
authors.lastname: King
authors.forename: Barry
authors.initials: B
authors.lastname: Bernstein
authors.forename: Paul
authors.initials: P
authors.lastname: Cernohous
authors.forename: Eric
authors.initials: E
authors.lastname: Bauer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moseley
authors.forename: Kai
authors.initials: K
authors.lastname: Gu
authors.forename: Ann
authors.initials: A
authors.lastname: Hsu
authors.forename: Scott
authors.initials: S
authors.lastname: Brun
authors.forename: Eugene
authors.initials: E
authors.lastname: Sun
mesh_terms: D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D014943:Global Health; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D061466:Lopinavir; D009154:Mutation; D019888:Nelfinavir / Q000627:therapeutic use*; D010349:Patient Compliance; D011744:Pyrimidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use*; D013997:Time Factors; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D018119:Stavudine; D019888:Nelfinavir; D019438:Ritonavir