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转换为固定剂量阿巴卡韦/拉米夫定或替诺福韦/恩曲他滨的HIV-1感染患者的身体成分和线粒体DNA变化：BICOMBO试验的一项子研究

Changes in body composition and mitochondrial DNA in HIV-1-infected patients switching to fixed-dose abacavir/lamivudine or tenofovir/emtricitabine: a substudy of the BICOMBO trial.

作者信息

Curran Adrian, Martinez Esteban, Podzamczer Daniel, Lonca Montserrat, Barragan Patricia, Crespo Manuel, Falco Vicenç, Vidal-Sicart Sergio, Imaz Arkaitz, Martinez Maria, Gatell Jose Maria, Ribera Esteban

机构信息

Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

出版信息

Antivir Ther. 2012;17(4):711-8. doi: 10.3851/IMP2081. Epub 2012 Feb 28.

DOI:10.3851/IMP2081

PMID:22374987

Abstract

BACKGROUND

Fat distribution, bone mineral density (BMD) and mitochondrial DNA (mtDNA) may improve, in the long-term, after switching from nucleoside reverse transcriptase inhibitors (NRTIs) to fixed-dose abacavir (ABC)/lamivudine (3TC) or tenofovir (TDF)/emtricitabine (FTC).

METHODS

This was a prospective, randomized, open-label, multicentre substudy of the BICOMBO trial in which virologically suppressed patients had their NRTIs switched to ABC/3TC or TDF/FTC. Whole-body dual-energy X-ray absorptiometry (DXA) was used to measure limb, trunk and total body fat and total BMD. Lumbar and hip DXA scans were used to measure lumbar and hip BMD. Fat mass ratio (FMR; % trunk fat/% leg fat by whole-body DXA) was used to assess fat distribution. mtDNA was measured in peripheral blood mononuclear cells (PBMCs). Parameters of interest were measured at baseline, 48 and 96 weeks, and were compared between treatment groups.

RESULTS

Of 56 patients included, 45 (20 ABC/3TC and 25 TDF/FTC) completed the substudy. After 96 weeks, ABC/3TC (+756 g, +12.1%) and TDF/FTC (+337 g, +7.6%) led to non-significantly different increases in limb fat (P=0.60). By contrast, trunk fat showed a significant increase (P=0.04) with ABC/3TC (+1,184 g, +10.6%) relative to TDF/FTC (-370 g, -4.2%). Median (IQR) FMR remained unchanged with ABC/3TC (-0.01 [-0.16-0.06]; P=0.23), but it decreased significantly with TDF/FTC (-0.13 [-0.30-0.00]; P=0.007). Total BMD and mtDNA significantly increased after 96 weeks, without differences between groups.

CONCLUSIONS

Switching from NRTIs to either ABC/3TC or TDF/FTC led to similar increases in limb fat, BMD and PBMC mtDNA after 96 weeks.

摘要

背景

从核苷类逆转录酶抑制剂（NRTIs）转换为固定剂量的阿巴卡韦（ABC）/拉米夫定（3TC）或替诺福韦（TDF）/恩曲他滨（FTC）后，长期来看，脂肪分布、骨矿物质密度（BMD）和线粒体DNA（mtDNA）可能会得到改善。

方法

这是BICOMBO试验的一项前瞻性、随机、开放标签、多中心子研究，在该试验中，病毒学抑制的患者将其NRTIs转换为ABC/3TC或TDF/FTC。采用全身双能X线吸收法（DXA）测量四肢、躯干和全身脂肪以及总骨密度。腰椎和髋部DXA扫描用于测量腰椎和髋部骨密度。脂肪质量比（FMR；通过全身DXA测量的%躯干脂肪/%腿部脂肪）用于评估脂肪分布。在外周血单核细胞（PBMCs）中测量mtDNA。在基线、48周和96周时测量感兴趣的参数，并在治疗组之间进行比较。

结果

纳入的56例患者中，45例（20例ABC/3TC和25例TDF/FTC）完成了子研究。96周后，ABC/3TC（增加756克，增加12.1%）和TDF/FTC（增加337克，增加7.6%）导致四肢脂肪增加，差异无统计学意义（P=0.60）。相比之下，ABC/3TC组（增加1184克，增加10.6%）的躯干脂肪相对于TDF/FTC组（减少370克，减少4.2%）有显著增加（P=0.04）。ABC/3TC组的中位（IQR）FMR保持不变（-0.01[-0.16 - 0.06]；P=0.23），但TDF/FTC组显著降低（-0.13[-0.30 - 0.00]；P=0.007）。96周后，总骨密度和mtDNA显著增加，组间无差异。