Department of Infectious Diseases, Inflammation Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Clinical Chemistry, University of Jyväskylä, Jyväskylä, Finland.
AIDS Patient Care STDS. 2021 Sep;35(9):335-341. doi: 10.1089/apc.2021.0106.
Integrase inhibitors appear to increase body weight, but paradoxically some data indicate that raltegravir (RAL) may decrease liver fat. Our objective was to study the effects of switching from a protease inhibitor (PI) or efavirenz (EFV) to RAL on liver fat, body composition, and metabolic parameters among people living with HIV (PLWH) with high risk for nonalcoholic fatty liver disease (NAFLD). We randomized overweight PLWH with signs of metabolic syndrome to switch a PI or EFV to RAL ( = 19) or to continue unchanged antiretroviral therapy (control, = 24) for 24 weeks. Liver fat was measured by magnetic resonance spectroscopy (MRS), body composition by magnetic resonance imaging, and bioimpedance analysis; subcutaneous fat biopsies were obtained. Median (interquartile range) liver fat content was normal in RAL 2.3% (1.1-6.0) and control 3.1% (1.6-7.3) group at baseline. Liver fat and visceral adipose tissue remained unchanged during the study. Body weight [from 85.9 kg (76.1-97.7) to 89.3 (78.7-98.7), = 0.019], body fat mass [from 20.3 kg (14.6-29.7) to 22.7 (17.0-29.7), = 0.015], and subcutaneous adipose tissue (SAT) volume [from 3979 mL (2068-6468) to 4043 (2206-6433), = 0.048] increased, yet, adipocyte size [from 564 pL (437-733) to 478 (423-587), = 0.019] decreased in RAL but remained unchanged in control group. Circulating lipids and inflammatory markers improved in RAL compared to control group. The median liver fat measured by MRS was unexpectedly within normal range in this relatively small study population with presumably high risk for NAFLD contradicting high prevalence of NAFLD reported with other methods. Despite weight gain, increase in SAT together with decreased adipocyte size and reduced inflammation may reflect improved adipose tissue function. Clinical Trial Registration number: NCT03374358.
整合酶抑制剂似乎会增加体重，但矛盾的是，一些数据表明拉替拉韦（RAL）可能会减少肝脂肪。我们的目的是研究在代谢综合征高危的 HIV 感染者（PLWH）中，从蛋白酶抑制剂（PI）或依非韦伦（EFV）转换为 RAL 对肝脂肪、身体成分和代谢参数的影响。我们将超重且有代谢综合征迹象的 PLWH 随机分为两组，一组将 PI 或 EFV 转换为 RAL（ = 19），另一组继续使用不变的抗逆转录病毒治疗（对照组， = 24），为期 24 周。通过磁共振光谱（MRS）测量肝脂肪，通过磁共振成像和生物电阻抗分析测量身体成分，并获取皮下脂肪活检。RAL 组和对照组的基线肝脂肪含量中位数（四分位距）分别为 2.3%（1.1-6.0）和 3.1%（1.6-7.3），均处于正常范围内。研究期间肝脂肪和内脏脂肪组织保持不变。体重[从 85.9 kg（76.1-97.7）增加到 89.3（78.7-98.7）， = 0.019]、体脂质量[从 20.3 kg（14.6-29.7）增加到 22.7（17.0-29.7）， = 0.015]和皮下脂肪组织（SAT）体积[从 3979 mL（2068-6468）增加到 4043（2206-6433）， = 0.048]，然而，RAL 组的脂肪细胞大小[从 564 pL（437-733）减少到 478（423-587）， = 0.019]，对照组则保持不变。与对照组相比，RAL 组的循环脂质和炎症标志物有所改善。在这项相对较小的研究中，通过 MRS 测量的肝脂肪中位数出人意料地处于正常范围内，该研究人群推测有很高的非酒精性脂肪性肝病（NAFLD）风险，这与其他方法报告的高 NAFLD 患病率相矛盾。尽管体重增加，但 SAT 的增加，加上脂肪细胞大小的减少和炎症的减少，可能反映了脂肪组织功能的改善。临床试验注册号：NCT03374358。
