February 5, 2001
Thalidomide is used to treat HIV-related aphthous ulcers in the mouth and esophagus, and also may have a role in the treatment of the wasting syndrome. An immunomodulator, it appears to work through alteration of cytokines such as TNF-alpha, although its mechanism of action is certainly more complex and is still not fully understood. Both its well-known teratogenecity as well as several common subjective side effects, which include sedation, rash, constipation, and peripheral neuropathy, have limited the use of thalidomide. However, considerable interest remains about the potentially salutory effects of thalidomide on HIV-related immune function.
In order to explore this concept further, researchers at Rockefeller University took cells from HIV-positive patients who also had CMV. These cells were then exposed to HIV and CMV antigens under three conditions: without any treatment, with the addition of thalidomide, and with an experimental analogue of the drug that is in the early phases of development and is hoped to have no teratogenic effects and fewer side effects. The experiment showed that the treated cells (both with thalidomide and the analogue) consistently had higher numbers of virus-specific, cytokine-secreting CD8 cells -- cells which are known to be critical for control of HIV replication.
As an extension of the above findings, thalidomide was given at a dose of 200mg a day for three weeks to two patients who were on combination antiretroviral therapy and had a viral load <50 copies. In both patients, there was a marked boosting of the number of virus-specific CD8 cells during thalidomide therapy.
While the bulk of the information presented in this poster was based on in vitro experiments, and must be considered preliminary, the principal investigator stated that the data would form the basis for a clinical study evaluating the immune effects of thalidomide in patients with suppressed viral load. It is possible that in the future immunomodulators such as thalidomide -- especially if less toxic alternatives are developed -- will become an important adjunct to standard antiretroviral therapy.