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The immunomodulatory effects of thalidomide on human immunodeficiency virus-infected children
W A Hanekom1, J Hughes, P A Haslett
1Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021, USA. hanekow@rockefeller.edu
Insights
Low-dose thalidomide is safe for HIV-infected children, showing no effect on viral load but boosting CD8+ T cells. This study highlights thalidomide
Area of Science:
- Pediatric Immunology
- Infectious Diseases
- Pharmacology
Background:
- Human immunodeficiency virus (HIV) infection in children presents unique challenges.
- Understanding immunomodulatory effects of therapeutic agents is crucial for pediatric HIV management.
Purpose of the Study:
- To evaluate the safety and immune effects of low-dose thalidomide in HIV-infected children.
- To assess thalidomide's impact on viral load and T-cell activation markers.
Main Methods:
- A study involving 8 HIV-infected children (7-69 months old) receiving low-dose thalidomide (3 mg/kg/day for 28 days).
- Assessed viral load, CD8+ T-cell activation markers (CD38, HLA-DR), and memory cell markers (CD45RO).
- Monitored HIV gag-specific CD8+ T-cell frequency and clinical adverse events.
Main Results:
- Thalidomide treatment did not alter viral load in children not on antiretroviral therapy.
- Significant stimulation of CD8+ T cells observed, with increased expression of activation and memory markers.
- Increased frequency of HIV gag-specific CD8+ T cells noted in a subset of children.
Conclusions:
- Low-dose thalidomide is safe and well-tolerated in HIV-infected children.
- Thalidomide demonstrates immunomodulatory effects, enhancing CD8+ T-cell responses.
- This is the first report suggesting thalidomide may improve HIV-specific CD8+ T-cell function in children.
Abstract:
The safety and immune effects of low-dose thalidomide treatment (3 mg/kg/day for 28 days) were evaluated in a study involving 8 South African human immunodeficiency virus (HIV)-infected children. The children were 7-69 months old and in disease stages A1-C3. Thalidomide therapy did not affect virus load, even though none of the children was receiving antiretroviral therapy. Thalidomide stimulated CD8+ T cells in peripheral blood, which increased expression of the activation markers CD38 and human leukocyte antigen DR and of the memory cell marker CD45RO. The frequency of HIV gag-specific CD8+ T cells in peripheral blood increased in 3 of 4 children who were evaluated during treatment with thalidomide. Clinical adverse events were mild. In this study, thalidomide was found to be safe and well tolerated and caused significant immunomodulation at a low dose. This is the first report describing use of an oral drug that may enhance HIV-specific CD8+ T cell function in HIV-infected children.