Placebo-Controlled Trial of Cyclosporin-A in HIV-1 Disease: Implications for Solid Organ Transplantation

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 29; no. 4; pp. 356 - 362
• Main Authors: Calabrese, Leonard H, Lederman, Michael M, Spritzler, John, Coombs, Robert W, Fox, Lawrence, Schock, Barbara, Yen-Lieberman, Belinda, Johnson, Ronald, Mildvan, Donna, Parekh, Namita
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-04-2002; Lippincott Williams & Wilkins; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adult; Biological and medical sciences; CD4 Lymphocyte Count; Clinical trials; Cyclosporine - adverse effects; Cyclosporine - immunology; Cyclosporine - therapeutic use; Double-Blind Method; Drug therapy; Experimental viral diseases and models; Female; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - physiology; Human immunodeficiency virus; Human viral diseases; Humans; Immune system; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - immunology; Immunosuppressive Agents - therapeutic use; Infectious diseases; Male; Medical sciences; Organ Transplantation; RNA, Viral - blood; Transplants & implants; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Allergy; HIV-1 virus; Toxicity; Vision disorder; Transplantation; Interleukin 2; Antiviral; Ciclosporin; Human; Immunopathology; Use; Cytokine; Retroviridae; AIDS; Delayed hypersensitivity; Immune deficiency; Lentivirus; Infection; Virus; Eye disease; Treatment; Viral disease; Blindness; Human immunodeficiency virus; Lymphocyte
• ISSN: 1525-4135; 1944-7884
• DOI: 10.1097/00126334-200204010-00005

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 × 10/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