Development and application of a genotypic AZT resistance assay: quantitative assessment of the resistance profile of clinical samples and the relative predictive ability of a resistance index.
OBJECTIVE
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.
Kyriakides
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TC
Department of Epidemiology and Public Health, Yale Unversity School of Medicine, New Haven, Connecticut, USA. tassos@connix.com
Heimer
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RR
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D004352:Drug Resistance, Microbial / Q000235:genetics / Q000276:immunology*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D009154:Mutation; D011446:Prospective Studies; D015203:Reproducibility of Results; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine