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HIV & AIDS
Immunosuppressive Effects of Drug Therapies Common in HIV-infected Patients
a report by
David J Feola, PharmD, PhD
1
and Alice C Thornton, MD
2
1. Assistant Professor, Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy;
2. Associate Professor, Division of Infectious Diseases, Department of Internal Medicine, University of Kentucky College of Medicine
High Risk for Drug Toxicity expression on the surface of these progenitors and by decreasing the
Advances in the treatment of HIV infection have increased patient survival expression of TNF-α.
5
In addition, the virological control that results from
rates and decreased morbidity and mortality. With the availability of more ART decreases the incidence of AIDS-associated neoplasms—including
effective antiretroviral regimens, researchers and clinicians have prolonged Kaposi’s sarcoma and non-Hodgkin’s lymphoma—through the restoration
the time interval during which viral replication is controlled and therefore of immune surveillance for cells that have undergone oncogenic
effective immune function is maintained, prohibiting opportunistic transformation.
6,7
infections (OIs) and other complications of HIV infection. As a result, these
patients undergo long-term exposure to a large number of drugs, Simultaneously, bone marrow suppression in this patient population can
be caused by a variety of insults. In addition to the effects of the virus
itself, iatrogenic suppression from HIV therapy, neoplasms, malnutrition,
and some OIs can adversely affect bone marrow cell survival and
Clinicians should have an understanding
replication.
8
This can result in anemia, thrombocytopenia, lymphopenia,
and neutropenia, which increase in incidence in patients who have
of the potential impact of drug therapy
progressed to AIDS. In addition to viral effects, drug regimens also have
on the bone marrow and overall
significant harmful effects on immune functions. Zidovudine (AZT) is
associated with the most potent myelosuppressive effects among
immunosuppression in patients
available antiretrovirals.
9,10
The reported clinical incidence of bone
infected with HIV.
marrow toxicities associated with AZT—including anemia, neutropenia,
and granulocytopenia—ranges from 2 to 45%.
11–13
Several groups have
shown that AZT affects lymphocytes in their early stages of development
in the bone marrow.
14–16
The monophosphorylated form of the drug is
including those that comprise antiretroviral therapy (ART), antibiotic responsible for its toxicity through a mechanism of thymidylate kinase
therapy for the prophylaxis and treatment of OI, and adjunct treatments inhibition, which lowers intracellular thymidine pools,
14
which in turn is
for additional disease states. While agents in each category have been associated with an inhibition of the highly replicating hematopoietic
shown to be extremely effective, certain agents have adverse progenitors in the bone marrow.
15,16
consequences on immune function, with many causing toxicity to the
bone marrow. The degree to which this has an impact on patient care has
David J Feola, PharmD, PhD, is an Assistant Professor in the
not been systematically investigated. However, clinicians should have an
Department of Pharmacy Practice and Science at the
understanding of the potential impact of drug therapy on the bone University of Kentucky College of Pharmacy. His research
marrow and overall immunosuppression in patients infected with HIV.
focuses on the immunotoxicity and immunomodulation of
therapeutic agents in the contexts of both HIV disease and
Iatrogenic immunosuppression from drug exposure could adversely
cystic fibrosis. Dr Feola received both of his degrees from the
influence the outcome of HIV therapy, as well as enhancing patient University of Kentucky, where his research involved the
susceptibility to OI and malignancy.
synergistic bone marrow toxicity of zidovudine and
sulfamethoxazole–trimethoprim. He has held board-certified
pharmacotherapy specialist status since 2001.
Antiretroviral Therapy and Bone Marrow
ART controls viral replication in infected patients by targeting a variety of
Alice C Thornton, MD, is an Associate Professor in the Division
viral processes, thereby increasing CD4
+
T-cell counts and improving
of Infectious Diseases, Department of Internal Medicine at the
patient survival.
1–3
ART also has several positive effects on the bone University of Kentucky College of Medicine. She is also the
marrow of infected individuals. HIV infection increases the apoptosis rate
Director of the Bluegrass Care Clinic, which serves the HIV-
infected population of the central Kentucky area. Dr Thornton
of CD34
+
progenitor cells in the bone marrow through an increased
received her medical degree from the Marshall University
surface expression of Fas, a ‘death receptor’ through which cells are School of Medicine and completed her residency training at
stimulated to undergo apoptosis, and an overproduction of tumor
Wake Forest University and an infectious diseases fellowship
at the Indiana University Medical Center.
necrosis factor-α (TNF-α), a cytokine that can also increase apoptosis
rates.
4,5
ART has been shown to limit this destruction by decreasing Fas
© T OUCH BRIEFINGS 2007
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