Hematologic Complications of HIV Infection
Hematologic Complications of HIV Infection
The article by Hambleton provides a compendium of the causes of hematopoietic defects in HIV-infected individuals. For the busy practicing physician who treats patients with HIV, these defects are not trivial. Cytopenias are a continuous problem that impact on most clinical decisions. For example, anemia and neutropenia are more common in patients with 100 CD4 cells/mcL or less. In general, these patients also have the highest titers of virus and are at greatest risk of developing symptomatic Mycobacterium avium or cytomegalovirus infection. Thus, physicians often find themselves trying to decide which patients should undergo a more extensive evaluation and which should receive "less" myelosuppressive therapy.
Compromises in treatment are made. Instead of using zidovudine (Retrovir) and lamivudine (3TC), doctors choose ddI (didanosine [Videx]) and stavudine (d4T [Zerit]). Instead of using rifabutin (Mycobutin), they use clarithromycin (Biaxin). Instead of using ganciclovir (Cytovene), they use foscarnet (Foscavir). While some of these alternatives are relatively interchangeable in efficacy, the limitations imposed by cytopenias must ultimately affect patients' quantity and quality of life.
Effective Therapies Available for Nearly All Complications
Fortunately, effective therapies are available for nearly all of these complications. Parvovirus infection (which is underdiagnosed) can be detected with DNA polymerase chain reaction (PCR) and can be eliminated with high-dose gamma globulin. Infection with M avium can be treated with clarithromycin-based regimens, which prolong survival. Cytomegalovirus infection can be treated with the combination of ganciclovir and foscarnet or cidofavir.
Both granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) and granulocyte-macrophage CSF (GM-CSF, sargramostim [Leukine]) increase white blood cell counts, protect against the development of neutropenia, reverse existing neutropenia, and increase both the duration and amount of myelosuppressive drugs that patients with HIV infection can tolerate [1,2]. Erythropoietin (Epogen, Procrit), an underutilized therapy, increases hematocrit, decreases transfusion requirements, and improves work capacity, energy level, and quality of life in anemic patients with HIV infection. In the not too distant future, thrombocytopenia may be treated with thrombopoietin.
Appropriate Management of Hematologic Complications Has Assumed New Importance
The tremendous advances made in the comprehensive treatment of patients with HIV infections has come at some cost. As a consequence of the advances in antiretroviral therapy, such as the protease inhibitors, patients are living longer with more profound immunosuppression. In turn, the more advanced stages of HIV infection are more often complicated by cytopenias with causes such as those enumerated by Hambleton. Given the efficacy of hematopoietic therapy, the appropriate diagnosis of anemia, neutropenia, and (soon) thrombocytopenia has taken on new importance.
Erythropoietin, G-CSF, and GM-CSF are all licensed in the United States. Clinical trials of human stem-cell factor, flk ligand, hemin, and TPO (thrombopoeitin) are planned or underway. Undoubtedly, these additional cytokines will provide even more avenues of therapy. The optimism about HIV therapy is likely to continue as increases in survival are reported. Dealing with the complications of HIV and improving quality of life will become more important. As in the erythropoietin trials,3 hematopoietic treatment may soon become a matter of quality of life for many patients with HIV.
1. Groopman J, Mitsuyasu R, DeLeo M: Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med 317:593-598, 1987.
2. Miles, SA, Mitsuyasu RT, Moreno J, et al: Combined therapy with recombinant G-CSF and EPO decreases hematologic toxicity from zidovudine. Blood 77:2109-2117, 1991
3. Henry D, Beall G, Benson C: Recombinant human erythropoietin in the therapy of anemia associated with HIV infection and zidovudine therapy: Overview of four clinical trials. Ann Intern Med 117:739-748, 1992.