Hematopoietic Growth Factors

Suppression of leukocyte or erythrocyte production can be a limiting factor in treating HIV infection or its complications. This problem has become less limiting with newer antiretroviral therapies and better control of HIV-1. However, for those patients who do develop severe cytopenia, hematopoietic growth factors are useful in raising cell counts. It is clear that in most patients with anemia due to HIV infection and or concomitant AZT therapy, with baseline serum erythropoietin concentrations <500 mU per milliliter, recombinant erythropoietin increases the hemoglobin and reduces the transfusion requirement. Use of the myeloid growth factors, granulocyte colony-stimulating factor (G-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) to ameliorate leukopenia due to HIV infection and or therapy with AZT, interferon-alpha, ganciclovir, or cancer chemotherapy has also been successful. Use of G-CSF has recently been shown to modestly reduce bacterial infection rates in HIV-infected individuals with neutrophil counts between 750 and 1000/mm³.

The major issue in the safety profile of the myeloid growth factors relates to their potential effects on replication of HIV. In vitro data indicate that HIV replication is stimulated by GM-CSF but not G-CSF. The data conflict as to whether this phenomenon occurs in vivo, but there are data that indicate that GM-CSF combined with AZT does not result in any increase in HIV-1 viral load.

Recent trials have indicated that the lymphopoietic cytokine interleukin-2 (IL-2) may be used to enhance lymphoid cell numbers, particularly CD4-positive T lymphocytes. Intermittent use of this cytokine has been shown to raise CD4 counts with tolerable toxicity in patients whose baseline CD4 count is greater than 200 cells/mm³ . Use of concurrent antiretroviral therapy is necessary to prevent enhanced virus replication. Whether this cytokine results in any clinical benefit remains controversial, and this approach should still be regarded as experimental pending data on clinical outcomes.

Neoplasms that occur with increased frequency in the setting of HIV disease are KS, B-cell lymphoma, and squamous cell neoplasia of the anogenital region. Smaller, but statistically meaningful increases have also been noted in Hodgkin's disease, leiomyosarcoma (in children only), seminoma, and plasmacytoma. Clinical management of AIDS-associated neoplasia must balance therapy directed at HIV-1 and opportunistic infections, as well as the tumors.