Correlation of Clinical Progression in Human Immunodeficiency Virus-Infected Children with In Vitro Zidovudine Resistance Measured by a Direct Quantitative Peripheral Blood Lymphocyte Assay

A rapid method for determination of zidovudine resistance was developed and results were correlated with clinical outcome in human immunodeficiency virus (HIV)-infected children. The zidovudine susceptibilities of HIV-1 isolates from 34 children were determined through a direct quantitative peripheral blood lymphocyte assay and compared with results of the AIDS Clinical Trials Group resistance assay. Patients' peripheral blood lymphocytes were 5-fold diluted and cocultured with donor lymphocytes and varying concentrations of zidovudine. Isolates were defined as sensitive if inhibited by ≤1.0 μM zidovudine and resistant at >1.0 μM. Children (n = 21) with zidovudine-resistant virus had greater evidence of disease progression than did those with zidovudine-sensitive virus (n = 11) as demonstrated by failure to thrive (57% vs. 9%, P =.01) and opportunistic infections (48% vs. 0, P =.006). This assay may be useful as a screening tool for development of clinically relevant zidovudine resistance.