Wierzbicki Anthony S, Purdon Scott D, Hardman Timothy C, Kulasegaram Ranjababu, Peters Barry S
Department of Chemical Pathology, St. Thomas' Hospital, London, UK.
Curr Med Res Opin. 2008 Mar;24(3):609-24. doi: 10.1185/030079908X272742.
The introduction of highly active antiretroviral therapy (HAART) around 1996 markedly reduced mortality and morbidity from human immunodeficiency virus (HIV) infection. As life expectancy has improved, the chronic complications of HIV and HAART have become increasingly relevant.
This article provides an overview of the HIV-associated lipodystrophy, its pathogenesis and its clinical consequences (based on a search strategy in PubMed including literature published to November 2007).
Lipodystrophy syndrome is characterized by abnormal fat distribution syndrome associated with metabolic disturbances and includes insulin resistance, deranged glucose and lipid metabolism. It is associated with increased risks of progression to type 2 diabetes and cardiovascular disease. Robust diagnostic criteria are required for lipodystrophy, and subsequent prospective cohort studies and randomized controlled trials are then required to determine the etiology and prognosis of lipodystrophy, and to evaluate therapeutic interventions for this consequence of HAART. Therapies to improve insulin resistance have been tried but they are frequently ineffective, and are limited by potential toxicity in this population. Hence, current management options for HIV associated lipodystrophy are limited and are mostly based on avoidance of risk factors and switching of antiretroviral drugs.
As the '3 by 5 strategy' of providing HIV drugs to the developing world is implemented worldwide, the numbers of patients adhering to antiretroviral medicines is dramatically increasing. One must be aware that in reducing the burden of acute retroviral disease, the treatments proposed might lead to significant rates of metabolic complications and further exacerbation of the epidemic of diabetes and cardiovascular disease.
1996年左右引入的高效抗逆转录病毒疗法(HAART)显著降低了人类免疫缺陷病毒(HIV)感染导致的死亡率和发病率。随着预期寿命的提高,HIV及HAART的慢性并发症变得越来越重要。
本文概述了HIV相关脂肪代谢障碍、其发病机制及其临床后果(基于对PubMed的检索策略,包括截至2007年11月发表的文献)。
脂肪代谢障碍综合征的特征是与代谢紊乱相关的异常脂肪分布综合征,包括胰岛素抵抗、葡萄糖和脂质代谢紊乱。它与进展为2型糖尿病和心血管疾病的风险增加有关。脂肪代谢障碍需要可靠的诊断标准,随后需要进行前瞻性队列研究和随机对照试验,以确定脂肪代谢障碍的病因和预后,并评估针对HAART这一后果的治疗干预措施。改善胰岛素抵抗的疗法已经尝试过,但往往无效,且受该人群潜在毒性的限制。因此,目前针对HIV相关脂肪代谢障碍的管理选择有限,主要基于避免危险因素和更换抗逆转录病毒药物。
随着在全球范围内实施向发展中世界提供HIV药物的“3乘5战略”,坚持服用抗逆转录病毒药物的患者数量急剧增加。必须意识到,在减轻急性逆转录病毒疾病负担的同时,所提出的治疗方法可能会导致较高的代谢并发症发生率,并进一步加剧糖尿病和心血管疾病的流行。