title: Dual resistance to zidovudine and lamivudine in patients treated with zidovudine-lamivudine combination therapy: association with therapy failure.
abstract: Human immunodeficiency virus type 1 (HIV-1) strains dually resistant to zidovudine and lamivudine (3TC) may arise during zidovudine-3TC combination therapy. The objective of this cross-sectional study (n = 43 patients) was to test the association between therapy response (clinical and immunologic) to zidovudine-3TC and the level of phenotypic zidovudine resistance and zidovudine resistance-associated genotype of 3TC-resistant isolates. Other variables included were baseline CD4+ cell count, baseline Centers for Disease Control and Prevention (CDC) classification, virus load, and time receiving zidovudine. Phenotypic resistance was assessed using a recombinant virus assay. Genotypic analysis was based on population sequencing of plasma HIV-1. In a univariate analysis using a logistic regression model, it was found that therapy response was significantly associated with phenotypic and genotypic zidovudine resistance, baseline CD4+ cell count, and virus load. After adjustment for all variables, phenotypic resistance to zidovudine remained the only significantly associated factor, independent of baseline CD4+ cell count, baseline CDC classification, and virus load.
authors.affiliation: Zentrum der Inneren Medizin, Klinikum der J.W. Goethe-Universität, Frankfurt, Germany. miller@em.uni-frankfurt.de
authors.forename: V
authors.initials: V
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: Phillips
authors.forename: C
authors.initials: C
authors.lastname: Rottmann
authors.forename: S
authors.initials: S
authors.lastname: Staszewski
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: K
authors.initials: K
authors.lastname: Hertogs
authors.forename: M P
authors.initials: MP
authors.lastname: de Béthune
authors.forename: S D
authors.initials: SD
authors.lastname: Kemp
authors.forename: S
authors.initials: S
authors.lastname: Bloor
authors.forename: P R
authors.initials: PR
authors.lastname: Harrigan
authors.forename: B A
authors.initials: BA
authors.lastname: Larder
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine