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Immunosuppressive Effects of Drug Therapies Common in HIV-infected Patients
better tolerated than combining AZT with ganciclovir.
67
Nine percent of It is unknown, however, whether iatrogenic drug effects such as those of
patients given didanosine plus ganciclovir in this study developed dose- AZT and TMP/SMX contribute to this deficiency. We speculate that this
limiting hematological toxicity versus 28% of patients in the AZT plus drug–drug interaction could contribute to the impaired B-cell function
ganciclovir group. commonly seen in HIV patients.
Freund and colleagues investigated the combined toxicity of AZT and What the Future Holds
TMP/SMX in normal mice.
62
Macrophage and B-lymphocyte numbers in the While drug therapy has been extremely effective in decreasing morbidity
spleen, and red blood cells and granulocytes in the peripheral blood, were and improving the quality of life of patients infected with HIV, clinicians
decreased by treatment with TMP/SMX and AZT in combination, whereas and researchers must remember the harmful effects associated with
treatment with either agent alone had no effect on these parameters. Our many of the life-saving therapies for this complex disease state. Patients
research group has extended these studies to determine that TMP/SMX in should be treated cautiously with many of these drug combinations, and
combination with AZT significantly interferes with the development of any hematological abnormalities identified should be investigated as
B-lineage cells in the bone marrow of mice.
68,69
Cells undergoing a burst of potential iatrogenic reactions to the therapies being employed. The
proliferation during the pre-B-cell stage are the most sensitive to availability of newer antiretroviral medications—including abacavir,
combination exposure, indicative of the impact that both SMX and AZT emtricitabine, and enfuvirtide—offers a wider selection of agents that
have on DNA replication. Additionally, we have shown that AZT plus carry a lower risk of bone marrow toxicities. As these newer agents are
TMP/SMX exposure blunts antigen-specific antibody production to both being utilized at higher and higher rates, the need for AZT, which carries
influenza A and B in HIV-infected patients receiving the vaccine.
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Patients a majority of the toxicity in this group of drugs, is diminishing. However,
with AIDS have an abnormal B-cell response in that antibody production is more research in the area of antimicrobials for the treatment and
augmented causing a hypergammaglobulinemia,
50,71
but the ability of these prophylaxis of OI is needed, as adequate treatment options that bypass
patients to mount antigen-specific antibody responses is compromised.
72–75
these toxicities are limited. ■
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