Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia.
Clin Infect Dis. 2010 Sep 1;51(5):591-9. doi: 10.1086/655765.
Lipoatrophy and metabolic complications of treatment of human immunodeficiency virus (HIV) infection may share common associations with adipose tissue pathology and inflammation. To investigate these relationships, we undertook a large-scale study of adipose tissue, body composition, and metabolic outcomes among HIV-infected adult men at a tertiary hospital HIV cohort during the period 2001-2007.
Assessments included adipose biopsies (n = 211) for investigation of adipocyte mitochondrial DNA content, adipocytokine expression, and adipose macrophage content; and whole-body dual-energy x-ray absorptiometry (DEXA) scans (n = 225) for objective body composition changes; 138 individuals contributed both biopsy and DEXA data.
Compared with 78 treatment-naive control subjects, 98 zidovudine recipients (48%) and 49 stavudine recipients (67%) had leg fat measures <10% threshold value. Adipose samples associated with current stavudine or zidovudine (n = 99) revealed significant adipocyte mitochondrial DNA depletion, adipose tissue macrophage infiltration, and elevated proinflammatory cytokine levels, compared with samples from control subjects and nonthymidine nucleoside reverse-transcriptase inhibitor (NRTI) recipients (all P < .05). Improvements in adipose pathology after NRTI switching (n = 21 longitudinal samples) correlated with increased preswitch adipose inflammation and less severe fat loss (both P < .05). Elevated ratios of total to high-density lipoprotein cholesterol levels and Homeostatic Metabolic Assessment scores correlated independently with lipoatrophy severity (P < .05) and increased body mass index (P < .05) in thymidine NRTI-experienced individuals. No effect of demographic or HIV-related variables, or HIV protease inhibitor therapy exposure was detected.
Adipose tissue pathology and lipoatrophic fat loss are highly prevalent among recipients of stavudine- or zidovudine-based HIV treatment and are associated with adverse metabolic outcomes. Restoring adipose tissue health appears to be an important issue in the long-term treatment of this patient population.
人类免疫缺陷病毒（HIV）感染治疗中的脂肪萎缩和代谢并发症可能与脂肪组织病理学和炎症存在共同关联。为了研究这些关系，我们对 2001 年至 2007 年期间在一家三级医院 HIV 队列中接受 HIV 感染的成年男性进行了一项大规模的脂肪组织、身体成分和代谢结果研究。
评估包括脂肪活检（n=211）以研究脂肪细胞线粒体 DNA 含量、脂肪细胞因子表达和脂肪巨噬细胞含量；全身双能 X 射线吸收法（DEXA）扫描（n=225）以评估身体成分的客观变化；138 人同时提供了活检和 DEXA 数据。
与 78 名未经治疗的对照组相比，98 名齐多夫定（AZT）接受者（48%）和 49 名司他夫定（d4T）接受者（67%）的腿部脂肪量低于 10%的阈值。与对照组和非胸苷核苷逆转录酶抑制剂（NRTI）接受者相比，当前使用司他夫定或 AZT 的脂肪样本（n=99）显示出明显的脂肪细胞线粒体 DNA 耗竭、脂肪组织巨噬细胞浸润和升高的促炎细胞因子水平（均 P<0.05）。NRTI 转换后的脂肪病理学改善（n=21 个纵向样本）与转换前脂肪炎症增加和脂肪丢失程度减轻相关（均 P<0.05）。总胆固醇与高密度脂蛋白胆固醇比值和稳态代谢评估评分升高与脂肪萎缩严重程度独立相关（P<0.05），并与胸苷 NRTI 经验丰富的个体的体重指数增加相关（P<0.05）。未发现人口统计学或 HIV 相关变量或 HIV 蛋白酶抑制剂治疗暴露的影响。
基于司他夫定或 AZT 的 HIV 治疗的接受者中，脂肪组织病理学和脂肪萎缩性脂肪丢失非常普遍，并且与不良代谢结果相关。恢复脂肪组织健康似乎是该患者群体长期治疗的一个重要问题。
