Placebo-controlled trial of cyclosporin-A in HIV-1 disease: implications for solid organ transplantation.
OBJECTIVE
Earlier open-label clinical trials have provided conflicting data on the effects of cyclosporin-A (CsA) on the clinical course and immune status of patients with HIV disease. With the prospects for wider use of CsA in the setting of solid organ transplantation in HIV-infected persons, data on the safety and immunologic activity of this agent are needed. We report here the results of a randomized, double-blind, placebo-controlled trial to assess the safety and immunologic activity of CsA administration in early HIV disease.


METHODS
Twenty-eight patients with confirmed HIV infection, CD4 cell counts greater than 500 x 106/L, and plasma HIV RNA >600 copies/mL were randomized to receive 2 mg/kg of CsA (Neoral) twice daily or identical placebo for 12 weeks. Subjects were stratified for the presence or absence of stable concomitant antiviral therapy. The primary end point was the effect of therapy on immune activation as assessed by the levels of soluble interleukin-2 receptors. Secondary end points included safety and effects of treatment on plasma HIV RNA, CD4 cell count, and other markers of immune activation and function.


RESULTS
The low dose of CsA used in this study did not suppress immune activation or increase circulating CD4 cell counts. Delayed-type hypersensitivity responses were not affected; however, lymphocyte proliferative responses tended to decrease. CsA-treated patients experienced a small but significant rise in plasma HIV RNA levels.


CONCLUSIONS
Low-dose CsA has no benefit in patients with stable early HIV disease, and its administration may be associated with an increase in plasma HIV RNA. The use of CsA in HIV-infected patients undergoing organ transplantation should be undertaken with caution
Calabrese
Leonard H
LH
Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. calabrl@ccf.org
Lederman
Michael M
MM
Spritzler
John
J
Coombs
Robert W
RW
Fox
Lawrence
L
Schock
Barbara
B
Yen-Lieberman
Belinda
B
Johnson
Ronald
R
Mildvan
Donna
D
Parekh
Namita
N
D000328:Adult; D018791:CD4 Lymphocyte Count; D016572:Cyclosporine / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D016377:Organ Transplantation; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D012367:RNA, Viral; D016572:Cyclosporine