Jemsek Joseph G, Arathoon Eduardo, Arlotti Massimo, Perez Carlos, Sosa Nestor, Pokrovskiy Vadim, Thiry Alexandra, Soccodato Michael, Noor Mustafa A, Giordano Michael
Jemsek Clinic, Huntersville, NC 28078, USA.
Clin Infect Dis. 2006 Jan 15;42(2):273-80. doi: 10.1086/498505. Epub 2005 Dec 5.
Protease inhibitor treatment of human immunodeficiency virus (HIV)-infected individuals has been linked to the development of lipodystrophy. The effects of atazanavir on body fat distribution and related metabolic parameters were examined in antiretroviral-naive patients.
HIV-positive patients with CD4 cell counts > or = 100 cells/mm3 were randomized to 1 of 2 treatment arms: (1) atazanavir, 400 mg given once daily, plus efavirenz placebo; or (2) efavirenz, 600 mg given once daily, plus atazanavir placebo; each drug was administered with fixed-dose zidovudine (300 mg) and lamivudine (150 mg) given twice daily, and patients were treated for at least 48 weeks. Fat distribution measurements (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], and total adipose tissue [TAT], as measured by computed tomography; and appendicular fat, truncal fat, and total fat levels, as measured by dual-energy x-ray absorptiometry), metabolic measurements (cholesterol and fasting triglyceride levels), and measurements of insulin resistance (fasting glucose and fasting insulin levels) were made at baseline and at week 48 of treatment for a subgroup of 111 atazanavir recipients and 100 efavirenz recipients.
Atazanavir and efavirenz treatments resulted in minimal to modest increases in fat accumulation, as measured by VAT, SAT, TAT, appendicular fat, truncal fat, and total fat levels; results were comparable in both arms. In addition, atazanavir was associated with none of the metabolic abnormalities seen with many other protease inhibitors.
Use of atazanavir for 48 weeks neither resulted in abnormal fat redistribution in antiretroviral-naive patients nor induced other metabolic disturbances commonly associated with HIV-related lipodystrophy. Longer-term assessments (e.g., at 96 weeks) will be important to confirm these findings.
蛋白酶抑制剂用于治疗人类免疫缺陷病毒(HIV)感染者与脂肪代谢障碍的发生有关。本研究在初治抗逆转录病毒治疗的患者中检测了阿扎那韦对体脂分布及相关代谢参数的影响。
CD4细胞计数≥100个/mm³的HIV阳性患者被随机分为2个治疗组:(1)阿扎那韦组,每日1次,每次400mg,加用依非韦伦安慰剂;(2)依非韦伦组,每日1次,每次600mg,加用阿扎那韦安慰剂;每种药物均与固定剂量的齐多夫定(300mg)和拉米夫定(150mg)每日2次联合使用,患者接受至少48周的治疗。对111例接受阿扎那韦治疗的患者和100例接受依非韦伦治疗的患者亚组,在基线及治疗第48周时进行脂肪分布测量(通过计算机断层扫描测量内脏脂肪组织[VAT]、皮下脂肪组织[SAT]和总脂肪组织[TAT];通过双能X线吸收法测量四肢脂肪、躯干脂肪和总脂肪水平)、代谢测量(胆固醇和空腹甘油三酯水平)以及胰岛素抵抗测量(空腹血糖和空腹胰岛素水平)。
通过VAT、SAT、TAT、四肢脂肪、躯干脂肪和总脂肪水平测量,阿扎那韦和依非韦伦治疗导致脂肪堆积有轻微至中度增加;两组结果相当。此外,阿扎那韦未出现许多其他蛋白酶抑制剂所伴有的代谢异常。
初治抗逆转录病毒治疗的患者使用阿扎那韦48周既未导致异常脂肪重新分布,也未引起通常与HIV相关脂肪代谢障碍有关的其他代谢紊乱。进行长期评估(如96周时)对于证实这些发现很重要。