HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
AIDS. 2012 Nov 13;26(17):2165-74. doi: 10.1097/QAD.0b013e328358b279.
No randomized study has prospectively followed subcutaneous adipose tissue mitochondrial DNA (mtDNA) changes when starting thymidine nucleoside reverse transcriptase inhibitors (tNRTIs).
The Metabolic Effects of DIfferent CLasses of AntiretroviralS study randomized HIV-positive, treatment-naive male participants to start lopinavir/ritonavir (LPVr) with either zidovudine/lamivudine (ZDV/3TC) or nevirapine (NVP).
Regional body fat was assessed by dual energy x-ray absorptiometry and abdominal computed tomography at months 0, 3, 12, 24 and 36. In a molecular substudy, subcutaneous adipose tissue (SAT) biopsies were taken, with mtDNA quantified by quantitative PCR. Data were analyzed using repeated measures linear regression analyses.
Of 50 participants recruited (23 to LPVr/ZDV/3TC), 48 started therapy, and 37 participants (19 on LPVr/ZDV/3TC) enrolled in the substudy. At 36 months, the LPVr/ZDV/3TC group had significantly lower limb fat [6.4 kg (0.26) versus 7.3 kg (0.31), P = 0.017] and a trend toward lower abdominal SAT compared to the LPVr/NVP group [131 cm (6.86) versus 146 cm (6.33), P = 0.097]. Over 36 months, mtDNA declined in the LPVr/ZDV/3TC group [mtDNA region 1: -190 (95) copies/cell, P = 0.053, region 2: -269 (106) copies/cell, P = 0.016] but not within the LPVr/NVP group [region 1: +28 (99) copies/cell, P = 0.78, region 2: +51 (111) copies/cell, P = 0.65, between-group difference P < 0.01 for both measurements]. mtDNA was significantly lower in the LPVr/ZDV/3TC group at 36 months.
This is the first randomized study to prospectively demonstrate reductions in SAT mtDNA in patients initiating ZDV/3TC-containing antiretroviral therapy (ART) but not in those initiating nucleoside reverse transcriptase inhibitor-sparing ART containing NVP and protease inhibitor. That reductions in SAT mtDNA were also accompanied by lower limb fat suggests that use of ART not containing ZDV/3TC may help prevent development of peripheral lipoatrophy.
目前尚无研究前瞻性地观察起始使用胸苷核苷逆转录酶抑制剂（tNRTIs）时皮下脂肪组织线粒体 DNA（mtDNA）的变化。
代谢影响不同类别的抗逆转录病毒药物研究将 HIV 阳性、初治的男性参与者随机分配至洛匹那韦/利托那韦（LPVr）加齐多夫定/拉米夫定（ZDV/3TC）或奈韦拉平（NVP）组。
采用双能 X 射线吸收法和腹部计算机断层扫描在 0、3、12、24 和 36 个月时评估局部体脂。在分子亚研究中，取皮下脂肪组织（SAT）活检，用定量 PCR 定量 mtDNA。采用重复测量线性回归分析进行数据分析。
50 名参与者（23 名接受 LPVr/ZDV/3TC 治疗）中，48 名开始治疗，37 名（19 名接受 LPVr/ZDV/3TC 治疗）参加了亚研究。36 个月时，LPVr/ZDV/3TC 组的下肢脂肪明显减少[6.4 kg（0.26）比 7.3 kg（0.31），P = 0.017]，与 LPVr/NVP 组相比，腹部 SAT 也有降低的趋势[131 cm（6.86）比 146 cm（6.33），P = 0.097]。36 个月期间，LPVr/ZDV/3TC 组 mtDNA 下降[mtDNA 区 1：-190（95）拷贝/细胞，P = 0.053；区 2：-269（106）拷贝/细胞，P = 0.016]，但 LPVr/NVP 组无此变化[区 1：+28（99）拷贝/细胞，P = 0.78；区 2：+51（111）拷贝/细胞，P = 0.65；两组间差异 P < 0.01]。36 个月时 LPVr/ZDV/3TC 组 mtDNA 明显较低。
这是第一项前瞻性研究，表明起始使用 ZDV/3TC 包含的抗逆转录病毒治疗（ART）的患者的 SAT mtDNA 减少，但起始使用包含奈韦拉平（NVP）和蛋白酶抑制剂的不含核苷逆转录酶抑制剂的 ART 的患者未减少。SAT mtDNA 的减少还伴随着下肢脂肪减少，这表明使用不含 ZDV/3TC 的 ART 可能有助于预防外周脂肪萎缩的发生。
