IN-VITRO IMPROVEMENT OF BONE-MARROW-DERIVED HEMATOPOIETIC COLONY FORMATION IN HIV-POSITIVE PATIENTS BY ALPHA-D-TOCOPHEROL AND ERYTHROPOIETIN

The majority of patients with progressive HIV infection develop a seve re hematopoietic failure which is aggravated by the hematotoxic effect of azidothymidine (AZT) treatment. Since it was shown in a mouse mode l that alpha-D-tocopherol (vitamin E derivative) antagonizes the inhib itory influence of AZT on the growth of burst-forming units-erythrocyt e (BFU-E), it was the aim of this study to investigate whether alpha-D -tocopherol and high dosages of erythropoietin (EPO) increase the hema topoietic colony-forming capacity of bone marrow cells from patients w ith progressive HIV disease and especially if they reverse the inhibit ory effects of AZT. The data demonstrate that tocopherol (1-100 mu mol /l) significantly increases the growth of BFU-E and colony-forming uni ts granulocyte-monocyte (CFU-GM) from HIV-infected patients. This stim ulatory effect is dose-dependent (maximum at 30-100 mu mol/l) and only occurs when the agent is present from the beginning of the cultures. EPO (5-10 U/ml) also augments the numbers of BFU-E from HIV-infected p atients. Tocopherol equally ameliorates the growth of BFU-E and CFU-GM from the HIV-positive cohort in the presence of AZT (10-100 mu mol/l) . For healthy controls, no such increase was observed, either with toc opherol or with higher dosages of EPO. In conclusion, both tocopherol and EPO partially reverse the myelosuppressive action of AZT in HIV-po sitive patients.