A double-blind placebo-controlled phase II trial of thalidomide in asymptomatic HIV-positive patients: clinical tolerance and effect on activation markers and cytokines

AIDS Res Hum Retroviruses. 1997 Dec 10;13(18):1625-31. doi: 10.1089/aid.1997.13.1625.


A randomized double-blind, placebo-controlled study was performed to determine the safety, efficacy, and effect of thalidomide on a variety of immunological and biochemical parameters in asymptomatic human immunodeficiency virus (HIV)-positive patients. Nineteen male patients with elevated markers of immune activation and CD4 cell counts above 400/mm3 were randomized to either placebo or thalidomide at 100 mg/day for 24 weeks. However, only 3 (of 10) patients receiving thalidomide completed all 24 weeks compared to 6 (of 9) patients receiving placebo. This was mainly due to fatigue (somnolence is a recognized side effect), although this was also seen to a lesser extent in the placebo group and so may not be drug attributable. No significant changes in CD4/CD8 count, activation markers, TNF-alpha, or TNFR1 were observed. However, a nonsignificant trend toward inhibition of mitogen-induced TNF-alpha production was observed in the thalidomide arm. The lack of systemic effect and the lower tolerance of thalidomide (at this dose) in asymptomatic patients highlights the need for pharmacokinetic analysis to address possible absorption problems and the need for more potent and less toxic TNF-alpha inhibitors to be developed for use in this type of study.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Antigens, CD / metabolism
  • Biomarkers
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cytokines / metabolism
  • Double-Blind Method
  • Follow-Up Studies
  • HIV Seropositivity / drug therapy*
  • HIV Seropositivity / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Male
  • Neopterin / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Thalidomide / adverse effects
  • Thalidomide / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism
  • beta 2-Microglobulin / metabolism


  • Anti-HIV Agents
  • Antigens, CD
  • Biomarkers
  • CD4 Antigens
  • CD8 Antigens
  • Cytokines
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • beta 2-Microglobulin
  • Interleukin-10
  • Interleukin-4
  • Thalidomide
  • Neopterin
  • Interferon-gamma