Effect of antiviral drugs and hematopoietic growth factors on in vitro erythropoiesis

Background: The purpose of these studies was to improve our understanding of nucleoside analog, antiviral, drug-induced anemia in HIV infection. Methods: Peripheral blood erythroid progenitor cells (BFU-E) from HIV-positive (HIV+) patients and normal donors were compared in methylcellulose cultures with erythropoietin, with and without antiviral drugs, and with and without the hematopoietic growth factors, stem cell factor (SCF), hemin, and interleukin-3 (IL-3). Results: Normal numbers of BFU-E-derived colonies were observed in cultures from HIV+ patients (mean ± 1 SD BFU-E/10⁵ cells plated: normal = 14.1 ± 7.9, HIV+ = 17.2 ± 14.2, p = 0.39). The antiviral drugs zidovudine (AZT), dideoxyinosine (ddI), and diedehydrodideoxythymidine (d4T) all inhibited erythroid colonies in HIV+ and normal cultures. AZT was the most erythropoietically inhibitory drug (AZT ID₅₀, mean ± 1 SD for normal cultures = 2.64 ± 4.15 μM, for HIV+ cultures = 6.28 ± 10.79 μM, p = 0.24). Hematologic toxicity was less with ddI and d4T. However, doses of ddI and d4T ≤ 10 μM inhibited colony growth in 9/14 and 8/12 cultures, respectively, from HIV+ patients. Conclusions: Stem cell factor (SCF), hemin, and interleukin-3 (IL-3) increased colony growth in HIV+ and normal cultures. In control cultures, hematopoietic growth factors added singly increased growth 1.3- to 8-fold. Hematopoietic growth factors increased growth even in cultures containing antiviral drugs. In some instances growth factors restored growth to control levels. SCF, hemin, and IL-3 were most effective when combined.