A RAPID, DIRECT TEST FOR ZIDOVUDINE SUSCEPTIBILITY IN CLINICAL ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) FROM INFECTED CHILDREN

Background: Existing phenotypic tests of antiretroviral susceptibility in clinical isolates of human immunodeficiency virus (HIV) are expens ive and slow, and require passage of virus in cell culture with the po ssible consequence of selecting variants. Objectives: We sought to dev elop a rapid 14-day assay for zidovudine susceptibility of cell-associ ated HIV performed directly in patient blood samples. Study design: Tw enty-three tests were performed prospectively in 21 children, and the results were compared with those of the AIDS Clinical Trials Group/Dep artment of Defense consensus drug susceptibility assay (DSA) as well a s certain clinical parameters. Results: Five strains from ZDV-naive ch ildren were sensitive by the rapid test. Three were tested by DSA, and all were sensitive. Six strains from children who had received greate r-than-or-equal-to 24 months of ZDV were resistant by the rapid assay. Four of these strains were tested by the DSA, and all were shown resi stant. The viral strains from children who received < 24 months of the rapy or who had switched from ZDV to other antiviral therapy exhibited variable sensitivity by both tests. Changes in CD4 cells in the subse quent 6 months, as well as weight gain during this time were both corr elated to the results of the rapid test. The syncytium-inducing capaci ty of the virus strains was analyzed similarly. Conclusions: The rapid intracellular virus susceptibility assay is a test of drug sensitivit y performed on HIV growing in cells obtained directly from an infected patient. The test has a two-week turn-around time and, in this prelim inary report, gives results which correlate with both time on zidovudi ne and also subsequent CD4 cell changes.