Calabrese Leonard H, Lederman Michael M, Spritzler John, Coombs Robert W, Fox Lawrence, Schock Barbara, Yen-Lieberman Belinda, Johnson Ronald, Mildvan Donna, Parekh Namita
Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
J Acquir Immune Defic Syndr. 2002 Apr 1;29(4):356-62. doi: 10.1097/00126334-200204010-00005.
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.
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.
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.
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
早期的开放标签临床试验关于环孢素A（CsA）对HIV疾病患者临床病程和免疫状态的影响提供了相互矛盾的数据。鉴于在HIV感染者实体器官移植中更广泛使用CsA的前景，需要有关该药物安全性和免疫活性的数据。我们在此报告一项随机、双盲、安慰剂对照试验的结果，以评估在早期HIV疾病中给予CsA的安全性和免疫活性。
28例确诊为HIV感染、CD4细胞计数大于500×10⁶/L且血浆HIV RNA>600拷贝/mL的患者被随机分为两组，一组每天两次接受2mg/kg的CsA（新山地明），另一组接受相同的安慰剂，为期12周。根据是否存在稳定的伴随抗病毒治疗对受试者进行分层。主要终点是通过可溶性白细胞介素-2受体水平评估的治疗对免疫激活的影响。次要终点包括安全性以及治疗对血浆HIV RNA、CD4细胞计数和其他免疫激活及功能标志物的影响。
本研究中使用的低剂量CsA并未抑制免疫激活或增加循环CD4细胞计数。迟发型超敏反应未受影响；然而，淋巴细胞增殖反应有下降趋势。接受CsA治疗的患者血浆HIV RNA水平有小幅但显著的升高。
低剂量CsA对早期HIV病情稳定的患者无益处，且其使用可能与血浆HIV RNA升高有关。在接受器官移植的HIV感染患者中使用CsA应谨慎。
