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重组人生长激素在HIV相关消瘦和恶病质中的作用:病理生理学及治疗原理

Role of recombinant human growth hormone in HIV-associated wasting and cachexia: pathophysiology and rationale for treatment.

作者信息

Gelato Marie, McNurlan Margaret, Freedland Eric

机构信息

Department of Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.

出版信息

Clin Ther. 2007 Nov;29(11):2269-88. doi: 10.1016/j.clinthera.2007.11.004.

Abstract

BACKGROUND

Wasting, or cachexia, is a significant, debilitating, and potentially life-threatening complication of HIV infection. It is associated with reduced strength and functional ability, reduced ability to withstand opportunistic infections, and increased risk of mortality. Although the incidence of HIV-associated wasting may have declined since the introduction of highly active antiretroviral therapy (HAART), it continues to be a concern in this patient population.

OBJECTIVE

This paper reviews available data on the etiology and clinical impact of HIV-associated wasting, the role of the growth hormone/insulin-like growth factor-I axis in the pathophysiology of this condition, and the rationale for its treatment with recombinant human growth hormone (rhGH).

METHODS

MEDLINE was searched for articles published in English through August 2007 using the terms HIV, wasting (and related terms), and growth hormone. Preference was given to clinical studies (including randomized clinical studies), meta-analyses, and guidelines. Review articles were evaluated and the bibliographies examined for additional relevant articles. The analysis was restricted to studies conducted in developed countries.

RESULTS

Alterations in the growth hormone/insulin like growth factor-I axis have been observed in patients with HIV-associated wasting, including elevated levels of the former and reduced levels of insulin-like growth factor I. In randomized, placebo-controlled studies, rhGH significantly improved lean body mass by approximately 3 kg compared with placebo (P < 0.001) and total body weight by approximately 3 kg (P < 0.001), and was associated with significant improvements in physical endurance and quality of life (P < 0.001). Common adverse events with rhGH therapy include blood glucose elevations, arthralgia (36.4%), myalgia (30.4%), and peripheral edema (26.1%), but these usually respond to dose reduction or drug discontinuation.

CONCLUSIONS

Physicians should be alert to the possibility of wasting in HIV-infected patients receiving HAART and should consider treatment to improve patients' stamina and quality of life. The evidence supports a role for rhGH in the treatment of patients with HIV-associated wasting. Regular blood glucose monitoring is advised when treating wasting with rhGH.

摘要

背景

消瘦,即恶病质,是HIV感染的一种严重、使人衰弱且可能危及生命的并发症。它与力量和功能能力下降、抵御机会性感染的能力降低以及死亡风险增加有关。尽管自高效抗逆转录病毒疗法(HAART)引入以来,HIV相关消瘦的发病率可能有所下降,但在这一患者群体中仍是一个令人担忧的问题。

目的

本文综述了关于HIV相关消瘦的病因和临床影响、生长激素/胰岛素样生长因子-I轴在该病症病理生理学中的作用以及用重组人生长激素(rhGH)治疗的理论依据的现有数据。

方法

通过检索MEDLINE,查找截至2007年8月以英文发表的文章,使用的检索词为HIV、消瘦(及相关术语)和生长激素。优先选择临床研究(包括随机临床研究)、荟萃分析和指南。对综述文章进行评估,并查阅参考文献以寻找其他相关文章。分析仅限于在发达国家进行的研究。

结果

在HIV相关消瘦患者中观察到生长激素/胰岛素样生长因子-I轴的改变,包括前者水平升高和胰岛素样生长因子I水平降低。在随机、安慰剂对照研究中,与安慰剂相比,rhGH使瘦体重显著增加约3千克(P<0.001),总体重增加约3千克(P<0.001),并与身体耐力和生活质量的显著改善相关(P<0.001)。rhGH治疗的常见不良事件包括血糖升高、关节痛(36.4%)、肌痛(30.4%)和外周水肿(26.1%),但这些通常通过减少剂量或停药得到缓解。

结论

医生应警惕接受HAART的HIV感染患者出现消瘦的可能性,并应考虑进行治疗以改善患者的耐力和生活质量。证据支持rhGH在治疗HIV相关消瘦患者中的作用。在用rhGH治疗消瘦时,建议定期监测血糖。

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