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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.
The article by Hambleton provides a compendium of the causes ofhematopoietic defects in HIV-infected individuals. For the busypracticing physician who treats patients with HIV, these defectsare not trivial. Cytopenias are a continuous problem that impacton most clinical decisions. For example, anemia and neutropeniaare more common in patients with 100 CD4 cells/mcL or less. Ingeneral, these patients also have the highest titers of virusand are at greatest risk of developing symptomatic Mycobacteriumavium or cytomegalovirus infection. Thus, physicians oftenfind themselves trying to decide which patients should undergoa 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 usingganciclovir (Cytovene), they use foscarnet (Foscavir). While someof 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 allof these complications. Parvovirus infection (which is underdiagnosed)can be detected with DNA polymerase chain reaction (PCR) and canbe eliminated with high-dose gamma globulin. Infection with Mavium can be treated with clarithromycin-based regimens, whichprolong survival. Cytomegalovirus infection can be treated withthe 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 thedevelopment of neutropenia, reverse existing neutropenia, andincrease both the duration and amount of myelosuppressive drugsthat 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 HIVinfection. In the not too distant future, thrombocytopenia maybe treated with thrombopoietin.
Appropriate Management of Hematologic Complications Has AssumedNew Importance
The tremendous advances made in the comprehensive treatment ofpatients with HIV infections has come at some cost. As a consequenceof the advances in antiretroviral therapy, such as the proteaseinhibitors, patients are living longer with more profound immunosuppression.In turn, the more advanced stages of HIV infection are more oftencomplicated by cytopenias with causes such as those enumeratedby Hambleton. Given the efficacy of hematopoietic therapy, theappropriate diagnosis of anemia, neutropenia, and (soon) thrombocytopeniahas taken on new importance.
Erythropoietin, G-CSF, and GM-CSF are all licensed in the UnitedStates. Clinical trials of human stem-cell factor, flkligand, hemin, and TPO (thrombopoeitin) are planned or underway.Undoubtedly, these additional cytokines will provide even moreavenues of therapy. The optimism about HIV therapy is likely tocontinue as increases in survival are reported. Dealing with thecomplications of HIV and improving quality of life will becomemore important. As in the erythropoietin trials,3 hematopoietictreatment may soon become a matter of quality of life for manypatients with HIV.
1. Groopman J, Mitsuyasu R, DeLeo M: Effect of recombinant humangranulocyte-macrophage colony-stimulating factor on myelopoiesisin the acquired immunodeficiency syndrome. N Engl J Med 317:593-598,1987.
2. Miles, SA, Mitsuyasu RT, Moreno J, et al: Combined therapywith recombinant G-CSF and EPO decreases hematologic toxicityfrom zidovudine. Blood 77:2109-2117, 1991
3. Henry D, Beall G, Benson C: Recombinant human erythropoietinin the therapy of anemia associated with HIV infection and zidovudinetherapy: Overview of four clinical trials. Ann Intern Med 117:739-748,1992.