RESUMO
OBJECTIVES: To develop and validate a rapid, genotypic, quantitative AZT resistance assay, and to evaluate the predictive ability of a resistance index. METHODS: AZT resistance profiles of paired samples from HIV-infected patients were determined by a ligase chain reaction (LCR) assay. AZT resistance levels and surrogate markers of HIV disease progression (viral load and CD4 counts) were used to compare AZT-naive and AZT-experienced patients. The ability of a "mutant/wild-type HIV-1 quasi-species" index to predict viral load was assessed. RESULTS: AZT resistance, evident at baseline in both AZT-experienced and AZT-naive patients, increased over 6 months of treatment. The resistance profile of AZT-naive patients differed from that of AZT-experienced patients ( p <.05); viral load and CD4 counts were similar. The relative predictive ability (for subsequent viral load) of the resistance index was similar to or higher than that of baseline viral load or CD4 count. CONCLUSIONS: This assay used to detect AZT resistance could be adapted for use with other antiretrovirals. The predictive ability of the proposed resistance index was equal to or surpassed that of viral load and CD4 count, lending further support to the use of resistance assays in selecting drug regimens both before and during antiretroviral therapy.
Assuntos
Fármacos Anti-HIV/farmacologia , Linfócitos T CD4-Positivos/imunologia , Resistência Microbiana a Medicamentos/imunologia , Infecções por HIV/imunologia , HIV-1/efeitos dos fármacos , Zidovudina/farmacologia , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Resistência Microbiana a Medicamentos/genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Humanos , Mutação , Estudos Prospectivos , Reprodutibilidade dos Testes , Carga Viral , Zidovudina/uso terapêuticoRESUMO
Changes in the susceptibility of bacterial pathogens and the availability of new antimicrobial drugs mean that physicians need to understand the underlying pharmacodynamics of each antimicrobial therapy. Antimicrobial pharmacodynamics determine clinical efficacy and should therefore be carefully considered when selecting appropriate antibiotic agents in the therapeutic setting.