HIV-1 drug resistance in subjects with advanced HIV-1 infection in whom antiretroviral combination therapy is failing: a substudy of AIDS Clinical Trials Group Protocol 388

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
Lisa M DemeterAIDS Clinical Trials Group Protocol 388

Abstract

We evaluated phenotypic and genotypic markers of drug resistance in human immunodeficiency virus type 1 (HIV-1) at the time of virologic failure (VF) in subjects in the AIDS Clinical Trials Group Protocol 388 (ACTG 388) who received lamivudine-zidovudine (or lamivudine-stavudine) and either indinavir, efavirenz-indinavir, or nelfinavir-indinavir. At VF, phenotypically susceptible HIV-1 was found in 55% of subjects in the nelfinavir-indinavir arm, compared with 22% in the indinavir arm (P=.006). Phenotypic resistance to lamivudine was less common in the efavirenz-indinavir arm (33% of subjects; P=.002) and the nelfinavir-indinavir arm (43%; P=.003), compared with the indinavir arm (78%). Isolated phenotypic resistance to efavirenz at VF occurred in HIV-1 recovered from 33% of subjects in the efavirenz-indinavir arm; 24% of the subjects had HIV-1 with both efavirenz and lamivudine resistance. Results of genotypic tests were similar. The lower frequency of resistance in the nelfinavir-indinavir arm likely reflects decreased drug exposure that is due to intolerance, which is consistent with the lower potency and tolerability of this combination in ACTG 388. The lower frequency of lamivudine resistance in the efavirenz-indinavir arm...Continue Reading

References

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Citations

Sep 10, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Daniel R Kuritzkes
Oct 16, 2007·Clinical Microbiology Reviews·Carrie Dykes, Lisa M Demeter
Mar 21, 2007·Expert Opinion on Drug Safety·Gabriele ArendtThorsten Nolting
May 30, 2007·Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research·R Scott BraithwaiteMark S Roberts
Dec 17, 2017·EMBO Molecular Medicine·Pargol HashemiIvan Sadowski

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