替诺福韦/恩曲他滨的降脂作用：一项随机、交叉、双盲、安慰剂对照试验。

The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover, double-blind, placebo-controlled trial.

机构信息

Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital Universitat Autònoma de Barcelona.

HIV Unit, Infectious Diseases Service, Bellvitge University Hospital, Bellvitge Biomedical Research Institute, Hospitalet de Llobregat.

出版信息

Clin Infect Dis. 2015 Aug 1;61(3):403-8. doi: 10.1093/cid/civ296. Epub 2015 Apr 13.

DOI:10.1093/cid/civ296

PMID:25870325

Abstract

BACKGROUND

It is unknown if tenofovir disoproxil fumarate (TDF), which is often coformulated with the lipid-neutral emtricitabine (FTC), has a lipid-lowering effect.

METHODS

We performed a randomized, crossover, double-blind, placebo-controlled clinical trial on human immunodeficiency virus type 1 (HIV-1)-infected subjects with HIV-1 RNA < 50 copies/mL during ≥6 months on stable darunavir/ritonavir (800/100 mg once daily) or lopinavir/ritonavir (400/100 mg twice daily) monotherapy, fasting total cholesterol (TC) ≥200 mg/dL or low-density lipoprotein cholesterol (LDL-c) ≥130 mg/dL, and no lipid-lowering drugs. In arm 1, TDF/FTC was added for 12 weeks, followed by 12 weeks of placebo (washout) and 12 additional weeks of placebo (placebo period). Subjects in arm 2 added placebo for 12 weeks (placebo period) followed by TDF/FTC for 12 weeks and placebo for 12 additional weeks (washout). The primary endpoint was change in median fasting TC levels.

RESULTS

Of 46 subjects enrolled, 56% received darunavir/ritonavir and 44% lopinavir/ritonavir. Exposure to TDF/FTC reduced TC from 234 to 205 mg/dL (P < .001), LDL-c from 155 to 128 mg/dL (P < .001), and high-density lipoprotein cholesterol (HDL-c) from 50.3 to 44.5 mg/dL (P < .001). It also decreased the proportion of subjects with fasting TC ≥200 mg/dL from 86.7% to 56.8% (P = .001), and LDL-c ≥130 mg/dL from 87.8% to 43.9% (P < .001). After 12 weeks, TDF/FTC exposure was associated with lower TC and LDL-c levels than placebo (P = .001 and P = .002, respectively). The TC/HDL-c ratio and triglyceride levels did not change with TDF/FTC exposure.

CONCLUSIONS

Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF.

CLINICAL TRIALS REGISTRATION

NCT01458977.

摘要

背景

富马酸替诺福韦二吡呋酯（TDF）常与脂溶性恩曲他滨（FTC）联合制成复方制剂，目前尚不清楚其是否具有降脂作用。

方法

我们对 HIV-1 载量＜50 拷贝/ml、已接受稳定剂量达芦那韦/利托那韦（800/100mg 每日 1 次）或洛匹那韦/利托那韦（400/100mg 每日 2 次）单药治疗≥6 个月、空腹总胆固醇（TC）≥200mg/dL 或低密度脂蛋白胆固醇（LDL-c）≥130mg/dL 且未使用降脂药物的 HIV-1 感染者进行了一项随机、交叉、双盲、安慰剂对照临床试验。试验组受试者加用 TDF/FTC 治疗 12 周，随后进行 12 周安慰剂洗脱期（安慰剂组），最后再进行 12 周安慰剂治疗（安慰剂期）。对照组受试者加用安慰剂治疗 12 周（安慰剂期），随后加用 TDF/FTC 治疗 12 周，再进行 12 周安慰剂洗脱期（安慰剂组）。主要终点为空腹 TC 中位数变化。

结果

共纳入 46 例受试者，56%接受达芦那韦/利托那韦治疗，44%接受洛匹那韦/利托那韦治疗。TDF/FTC 治疗使 TC 从 234mg/dL 降至 205mg/dL（P＜0.001），LDL-c 从 155mg/dL 降至 128mg/dL（P＜0.001），高密度脂蛋白胆固醇（HDL-c）从 50.3mg/dL 降至 44.5mg/dL（P＜0.001）。TDF/FTC 治疗还使空腹 TC≥200mg/dL 的受试者比例从 86.7%降至 56.8%（P=0.001），LDL-c≥130mg/dL 的比例从 87.8%降至 43.9%（P＜0.001）。TDF/FTC 治疗 12 周后，TC 和 LDL-c 水平均低于安慰剂组（P=0.001 和 P=0.002）。TC/HDL-c 比值和甘油三酯水平在 TDF/FTC 治疗期间无变化。