Antiretroviral Therapy and Immunomodulators in Patients with AIDS JEROME
E. GROOPMAN,
M.D.,
Boston, Massachusetts
A number of studies have illustrated the effectiveness of hematopoietic growth factors in managing treatment-related cytopenias in patients with human immunodeficiency virus (HIV) infection. One of these factors, granulocyte-macrophage colony-stimulating factor, has been shown to restore absolute neutrophil counts in patients with acquired immunodeficiency syndrome (AIDS) and Kaposi’s sarcoma receiving a combination of zidovudine (AZT) and interferon alfa. A combination of granulocyte colony-stimulating factor and erythropoietin has also been demonstrated to alleviate both neutropenia and anemia in patients with advanced AIDS or AIDS-related complex receiving zidovudine. Hematopoietic growth factors, in combination with each other and with antiretroviral agents, thus have an important supportive role to play in the treatment of patients with HIV disease.
From the Division of Hematology/Oncology, Department of Medicine, New England Deaconess Hospital and Harvard Medical School, Boston, Massachusetts. Requests for reprints should be addressed to Jerome E. Groopman, M.D., Division of Hematology/Oncology, New England Deaconess Hospital, 110 Francis Street, Boston, Massachusetts 02215.
4A-18s
April 10, 1991
The American Journal of Medicine
A
multilevel approach is optimal in the therapy of human immunodeficiency virus (HIV) disease. First, therapy must be directed against the opportunistic infections and malignancies that arise as a result of compromised immune function. Second, the HIV infection itself must be controlled. Finally, if progression of the disease is to be halted, damage to the patient’s immune system must be remedied. In the decade since HIV disease was first recognized, dramatic progress has been made in the first two of these areas. For example, with prophylactic use of aerosolized pentamidine, the incidence of Pneumocystis ccwinii pneumonia, a major cause of mortality in acquired immunodeficiency syndrome (AIDS) patients, has declined appreciably. Moreover, agents are now available that directly attack the underlying HIV infection. The success of several antiretroviral agents, most notably zidovudine (AZT), in suppressing HIV replication has not only resulted in increased patient survival but has challenged the belief that retroviruses are untreatable [l-4]. In contrast, little progress has been made in restoring compromised host defenses in patients with AIDS. A complicating factor has been that many of the drugs most successfully used to treat patients with AIDS-including zidovudine, pentamidine, ganciclovir, sulfur-based antibiotics, and interferon alfa-are themselves myelosuppressive. Thus, attempts to treat the underlying HIV infection and the associated diseases may further impair the patient’s already damaged immune system. Recent studies, however, have demonstrated that hematopoietic growth factors can alleviate the myelosuppressive effects of some antiretroviral therapies [5,6]. This article reviews the results of trials with three growth factors-granulocyte colony-stimulating factor (G-CSF), granulocytemacrophage colony-stimulating factor (GM-CSF), and erythropoietin-in the treatment of patients with AIDS.
ROLESOF THREEGROWTHFACTORSIN HEMATOPOIESIS G-CSF, GM-CSF, and erythropoietin are all growth factors with important roles in directing
Volume 90 (suppl 4A)
SYMPOSIUM
I
lOOr
ON COMBINATION
ANTIRETROVIRAL
THERAPY / GROOPMAN
--
80 60 -
Figure 1. Percent of vrral suppression in monocytes and macrophages treated with granulocyte-macrophage colony-stimulating factor (GMCSF) 100 U/ml (0) or without GM-W (0) from day -5 and exposed to human immunodeficiency virus in presence of four different dideoxynucleoside analogues of deoxythymidine. Results shown are the mean i SEM of three or more separate experiments, except in the case of D4T, which was evaluated in only two experiments, AZT = zidovudine; AZddU = 3’.azido-2’,3’-dideoxyuridine; ddT = 2’,3’-dideoxythymidine; d4T = 2’,3’-dideoxy-2’,3’-didehydrothymidine; n.e. = p value not evaluated; *p ~0.05; **p
E. GROOPMAN,
M.D.,
Boston, Massachusetts
A number of studies have illustrated the effectiveness of hematopoietic growth factors in managing treatment-related cytopenias in patients with human immunodeficiency virus (HIV) infection. One of these factors, granulocyte-macrophage colony-stimulating factor, has been shown to restore absolute neutrophil counts in patients with acquired immunodeficiency syndrome (AIDS) and Kaposi’s sarcoma receiving a combination of zidovudine (AZT) and interferon alfa. A combination of granulocyte colony-stimulating factor and erythropoietin has also been demonstrated to alleviate both neutropenia and anemia in patients with advanced AIDS or AIDS-related complex receiving zidovudine. Hematopoietic growth factors, in combination with each other and with antiretroviral agents, thus have an important supportive role to play in the treatment of patients with HIV disease.
From the Division of Hematology/Oncology, Department of Medicine, New England Deaconess Hospital and Harvard Medical School, Boston, Massachusetts. Requests for reprints should be addressed to Jerome E. Groopman, M.D., Division of Hematology/Oncology, New England Deaconess Hospital, 110 Francis Street, Boston, Massachusetts 02215.
4A-18s
April 10, 1991
The American Journal of Medicine
A
multilevel approach is optimal in the therapy of human immunodeficiency virus (HIV) disease. First, therapy must be directed against the opportunistic infections and malignancies that arise as a result of compromised immune function. Second, the HIV infection itself must be controlled. Finally, if progression of the disease is to be halted, damage to the patient’s immune system must be remedied. In the decade since HIV disease was first recognized, dramatic progress has been made in the first two of these areas. For example, with prophylactic use of aerosolized pentamidine, the incidence of Pneumocystis ccwinii pneumonia, a major cause of mortality in acquired immunodeficiency syndrome (AIDS) patients, has declined appreciably. Moreover, agents are now available that directly attack the underlying HIV infection. The success of several antiretroviral agents, most notably zidovudine (AZT), in suppressing HIV replication has not only resulted in increased patient survival but has challenged the belief that retroviruses are untreatable [l-4]. In contrast, little progress has been made in restoring compromised host defenses in patients with AIDS. A complicating factor has been that many of the drugs most successfully used to treat patients with AIDS-including zidovudine, pentamidine, ganciclovir, sulfur-based antibiotics, and interferon alfa-are themselves myelosuppressive. Thus, attempts to treat the underlying HIV infection and the associated diseases may further impair the patient’s already damaged immune system. Recent studies, however, have demonstrated that hematopoietic growth factors can alleviate the myelosuppressive effects of some antiretroviral therapies [5,6]. This article reviews the results of trials with three growth factors-granulocyte colony-stimulating factor (G-CSF), granulocytemacrophage colony-stimulating factor (GM-CSF), and erythropoietin-in the treatment of patients with AIDS.
ROLESOF THREEGROWTHFACTORSIN HEMATOPOIESIS G-CSF, GM-CSF, and erythropoietin are all growth factors with important roles in directing
Volume 90 (suppl 4A)
SYMPOSIUM
I
lOOr
ON COMBINATION
ANTIRETROVIRAL
THERAPY / GROOPMAN
--
80 60 -
Figure 1. Percent of vrral suppression in monocytes and macrophages treated with granulocyte-macrophage colony-stimulating factor (GMCSF) 100 U/ml (0) or without GM-W (0) from day -5 and exposed to human immunodeficiency virus in presence of four different dideoxynucleoside analogues of deoxythymidine. Results shown are the mean i SEM of three or more separate experiments, except in the case of D4T, which was evaluated in only two experiments, AZT = zidovudine; AZddU = 3’.azido-2’,3’-dideoxyuridine; ddT = 2’,3’-dideoxythymidine; d4T = 2’,3’-dideoxy-2’,3’-didehydrothymidine; n.e. = p value not evaluated; *p ~0.05; **p
