MYELOTOXICITY OF RIFABUTIN AND 3'-AZIDO-3'-DEOXYTHYMIDINE, ALONE AND IN COMBINATION, TO HUMAN HEMATOPOIETIC PROGENITOR CELLS-INVITRO

Mycobacterial infection is a common complication of acquired immunodef iciency syndrome (AIDS) frequently requiring antimycobacterial medicat ion. It was of interest to determine if one such agent, rifabutin, cou ld be tolerated by AIDS patients in conjunction with 3'-azido-3'-deoxy thymidine (AZT) therapy. We evaluated the in vitro myelotoxic effects of rifabutin on human hematopoietic progenitor cells, alone and in com bination with AZT (rifabutin: AZT, 1:10 ratio) over a range of concent rations in a microcapillary assay. Both rifabutin and AZT at 5 muM wer e moderately toxic to hematopoletic progenitors, inhibiting colony for mation by 57-65% and 59-63%, respectively. The combination of rifabuti n (5 muM) and AZT (50 muM) inhibited colony formation by 59-73%. Granu locyte-macrophage progenitors were less sensitive to this combination than erythroid progenitors. The combination of rifabutin and AZT did n ot exceed the in vitro myelotoxicity to human progenitors of AZT alone . These results suggest that rifabutin may be tolerated in AIDS patien ts, with no anticipated increase in myelotoxicity when given with AZT.