Dual resistance to zidovudine and lamivudine in patients treated with zidovudine-lamivudine combination therapy:: Association with therapy failure

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-I, 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.