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 less than or equal to 1.0 mu M zidovudine and resistant at >1.0 mu M 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.