University of Pittsburgh School of Medicine, PA 15213, USA.
Clin Infect Dis. 2012 Sep;55(5):631-8. doi: 10.1093/cid/cis463. Epub 2012 May 4.
The effect of peginterferon alpha/ribavirin (PEG-IFN/RBV) and hepatitis C virus (HCV) clearance on lipid and insulin resistance (IR) profiles in HCV/human immunodeficiency virus (HIV) coinfection is unknown.
We measured fasting total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoproteins (HDL-C), triglycerides (TG), glucose, and insulin at defined intervals in the A5178 study (N = 329), a prospective treatment trial in HCV/HIV coinfection. Changes from baseline and the relation between baseline values of these variables to sustained virologic response (SVR) were determined.
Of 182 subjects with metabolic data, 98 achieved early virologic response (EVR) and continued PEG-IFN/RBV. Among those, median pretreatment HCV RNA was 6.6 log(10 )IU/mL; 73% had HCV genotype 1. Median pretreatment TC was 176 mg/dL (interquartile range [IQR],150-205]; median LDL-C was 99 mg/dL (IQR, 79-123); median HDL-C was 40 mg/dL (IQR, 31-47); and median TG was 147 mg/dL (IQR, 101-221). Median homeostasis model assessment of IR (HOMA-IR) was 3.3 (IQR, 1.7-5.3). The EVRs demonstrated a decline in TC, LDL-C, and HDL-C, whereas TG increased on treatment but returned to near baseline 24 weeks after end of treatment (EOT). The HOMA-IR decline from entry to 24 weeks after EOT was significant among non-sustained virologic responders and nonsignificant among sustained virologic responders; this difference was offset after adjusting for higher HOMA-IR at baseline among the former. Among all 182 subjects, entry LDL-C was associated with SVR in a joint logistic model adjusted for HCV genotype, race, and prior IFN (odds ratio, 1.17 per 10 mg/dL increase; 95% confidence interval, 1.03-1.32), but TC, HDL, TG, and IR were not.
Peginterferon alpha and RBV can significantly affect lipid profile and IR in HCV/HIV-coinfected persons. Although the lipid profile returns to near pretreatment levels after completion of treatment, our data suggest persistent modest improvement in IR with treatment. Clinical Trials Registration. NCT00078403.
聚乙二醇干扰素 α/利巴韦林（PEG-IFN/RBV）和丙型肝炎病毒（HCV）清除对 HCV/人类免疫缺陷病毒（HIV）合并感染的脂质和胰岛素抵抗（IR）谱的影响尚不清楚。
我们在 A5178 研究（N=329）中以定义的间隔测量空腹总胆固醇（TC）、低密度脂蛋白（LDL-C）、高密度脂蛋白（HDL-C）、甘油三酯（TG）、葡萄糖和胰岛素，这是一项 HCV/HIV 合并感染的前瞻性治疗试验。确定从基线的变化以及这些变量的基线值与持续病毒学应答（SVR）之间的关系。
在有代谢数据的 182 名受试者中，98 名达到早期病毒学应答（EVR）并继续接受 PEG-IFN/RBV 治疗。其中，中位预处理 HCV RNA 为 6.6 log（10）IU/mL；73%为 HCV 基因型 1。中位预处理 TC 为 176 mg/dL（四分位距[IQR]，150-205）；中位 LDL-C 为 99 mg/dL（IQR，79-123）；中位 HDL-C 为 40 mg/dL（IQR，31-47）；中位 TG 为 147 mg/dL（IQR，101-221）。中位稳态模型评估的胰岛素抵抗（HOMA-IR）为 3.3（IQR，1.7-5.3）。EVR 显示 TC、LDL-C 和 HDL-C 下降，而 TG 在治疗期间增加，但在治疗结束后 24 周（EOT）时恢复到接近基线。在非持续病毒学应答者中，从入组到 EOT 后 24 周的 HOMA-IR 下降具有统计学意义，而在持续病毒学应答者中则无统计学意义；在调整前者中较高的 HOMA-IR 后，这种差异被抵消。在所有 182 名受试者中，在调整 HCV 基因型、种族和既往 IFN 的联合逻辑模型中，入组时的 LDL-C 与 SVR 相关（优势比，每增加 10 mg/dL 增加 1.17；95%置信区间，1.03-1.32），但 TC、HDL、TG 和 IR 则不然。
聚乙二醇干扰素 α 和 RBV 可显著影响 HCV/HIV 合并感染人群的脂质谱和 IR。尽管在治疗完成后，脂质谱恢复到接近预处理水平，但我们的数据表明，治疗后 IR 仍有持续适度改善。临床试验注册。NCT00078403。
