TreatmentUpdate80 - Vol. 8, No. 0; August 1997
Sean Hosein

People with AIDS can develop painful ulcers in the mouth/throat as a result of herpes or syphilis. In some cases, however, cells of the immune system attacking those locations can cause ulcers to form (called apthous ulcers). Treatment can include corticosteroids (eg. prednisone) either placed on the ulcer or taken as tablets. Not all people respond to this therapy and the ulcers often recur. As well, long-term use of corticosteroids may further weaken an immune system already damaged by HIV. Thalidomide was a drug used as a sedative in the 1960s, but was banned because its use during pregnancy led to birth defects. It is still used to treat complications due to leprosy and in the late 1980s doctors began to report that it could help some ulcers heal in PHAs. An American study ATCG 251 suggests that thalidomide is an effective treatment for apthous ulcers in the short term (4 weeks), but that it causes the level of HIV in the blood (viral load) to rise.

Study details

Researchers assigned 57 volunteers with AIDS to receive at random either (a) thalidomide 200 mg at bedtime (29 subjects) or (b) fake thalidomide (placebo) also taken at bedtime (28 subjects). Fifty subjects were male and 7 female. CD4+ cell counts were on average low, with 50% of subjects on thalidomide having 17 cells. The equivalent figure for the placebo group was 28 cells.

Results

* Fifty percent of subjects receiving thalidomide recovered from their ulcers within 4 weeks

* Seven percent of subjects on placebo had a similar experience

This difference between the two groups was statistically significant, that is, not likely due to chance alone. In looking at everyone who obtained some benefit from thalidomide doctors found that:

* ninety percent of subjects on thalidomide had either complete or partial recovery from ulcers

* Among subjects in the placebo group, the equivalent figure was 25%. Again this difference was statistically significant.

Seven subjects whose ulcers did not completely heal received thalidomide 400 mg/day, taken as 200 mg twice daily. Five subjects experienced a complete recovery. After 4 weeks, doctors offered subjects who had been receiving placebo thalidomide. Those subjects who accepted had the same rate of recovery as the first group who took thalidomide.

Weight gain

Volunteers on thalidomide during the first 4 weeks of the study gained nearly 2 kg of weight while those on placebo did not gain any weight.

Immune system

According to the researchers, "There were no important changes in CD4+ or CD8+ [cell counts during the 4 weeks of the study]." Levels of the chemical messenger TNF-alpha (tumour necrosis factor-alpha) rose significantly among subjects receiving thalidomide, but the importance of this change is not clear.

HIV

At the start of the study, the level of HIV among subjects assigned to receive thalidomide was 120,000 copies while among the placebo group it was 83,000 copies. At the end of the study viral load increased in the thalidomide group to approximately 171,252 copies, significantly more than in those on placebo.

Toxicity

Twenty-one percent of subjects taking thalidomide left the study because of the drug's toxicity. By the 4th week, researchers estimated that nearly 50% of subjects receiving thalidomide had to reduce their dose. Side effects commonly seen with thalidomide included:

* drowsiness

* rash

(Note that another article on the side effects of thalidomide appears in the section "Thalidomide")

Overall

Thalidomide is "clearly effective" in treating apthous ulcers. The study doctors, however, "urge caution in using thalidomide...after the 2 to 4 weeks of short term treatment," because of the drug's effect on increasing levels of HIV in the blood. Thalidomide can weaken the immune system's ability to control infections so it is not surprising that viral load rose. Although thalidomide is not licensed in Canada it is available through the Special Access programme (formerly known as the Emergency Drug Release Programme).

REFERENCES:

1. Jacobson JM, Greenspan JS, Spritzler J, et al. Thalidomide for the treatment of oral apthous ulcers in patients with human immunodeficiency virus infection. New England Journal of Medicine 1997;336:1487-1493.

2. McHugh SM, Rifkin IR, Deighton J, et al. The immunosuppressive drug thalidomide induces T helper cell Type 2 (Th2) and concomitantly inhibits Th1 cytokine production in mitogen- and antigen-stimulated human peripheral blood mononuclear cell cultures. Clinical and Experimental Immunology 1995;99:160-167.

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Copyright © 1997 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca