Wallis Robert S, Kalayjian Robert, Jacobson Jeffrey M, Fox Lawrence, Purdue Lynette, Shikuma Cecilia M, Arakaki Richard, Snyder Stuart, Coombs Robert W, Bosch Ronald J, Spritzler John, Chernoff Miriam, Aga Evgenia, Myers Laurie, Schock Barbara, Lederman Michael M
The University Medicine and Dentistry of New Jersey--New Jersey Medical School, Newark, USA.
J Acquir Immune Defic Syndr. 2003 Mar 1;32(3):281-6. doi: 10.1097/00126334-200303010-00006.
Adult Clinical Trials Group Study 349 examined the immunology, virology, and safety of 40 mg/d prednisone as an adjunct to antiretroviral therapy in 24 HIV-infected subjects with >200 CD4+ T cells/mm in a randomized placebo-controlled trial. After 8 weeks, median lymphocyte and CD4+ cell numbers increased >40% above baseline values (p =.08). No effect was observed on markers of cell activation or apoptosis, although the proportion of CD28+ CD8+ T cells increased (p =.006). Prednisone inhibited monocyte TNFalpha production without affecting T-cell responses to antigens or mitogens. Two subjects assigned to prednisone were subsequently found to have asymptomatic osteonecrosis of the hip. Many questions remain regarding the role of activation-induced sequestration and apoptosis as causes of progressive CD4+ T-cell loss in AIDS. The potential role of corticosteroids as tools to examine this question will be limited by concerns regarding their toxicity; however, further studies of other agents to limit cellular activation in AIDS are warranted.
成人临床试验组研究349在一项随机安慰剂对照试验中,对24名CD4+ T细胞计数>200个/mm的HIV感染受试者,研究了40mg/d泼尼松作为抗逆转录病毒疗法辅助药物的免疫学、病毒学及安全性。8周后,淋巴细胞和CD4+细胞数量中位数较基线值增加>40%(p = 0.08)。尽管CD28+ CD8+ T细胞比例增加(p = 0.006),但未观察到对细胞活化或凋亡标志物有影响。泼尼松抑制单核细胞TNFα产生,而不影响T细胞对抗原或丝裂原的反应。随后发现,两名分配接受泼尼松治疗的受试者出现无症状性髋部骨坏死。关于激活诱导隔离和凋亡作为艾滋病中CD4+ T细胞进行性丢失原因的作用,仍存在许多问题。皮质类固醇作为研究该问题工具的潜在作用,将因对其毒性的担忧而受到限制;然而,有必要进一步研究其他限制艾滋病中细胞活化的药物。