Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction.

Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction.
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DOI:
10.1371/journal.pone.0063623
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Maartens G
Maartens G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
de Waal R;Cohen K;Maartens G

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在接受抗逆转录病毒治疗(ART)的患者中经常观察到脂肪萎缩和/或中心脂肪增加。两者都被认为是抗逆转录病毒药物不良反应。我们进行了一项系统性回顾,以确定接受ART的HIV感染患者的脂肪减少或增加是否比未感染的对照组更常见;是否与特定的抗逆转录病毒药物相关;以及是否会在转换抗逆转录病毒药物后逆转。27项研究符合我们的纳入标准。一项队列研究报告,接受ART的HIV感染患者脂肪萎缩更多,皮下脂肪增加较少,但与对照组相比,中心脂肪增加无差异。随机对照试验(RCT)显示以下方案的肢体脂肪减少更多(或脂肪增加更少):司他夫定(与其他核苷逆转录酶抑制剂(NRTI)相比);依法韦仑(与蛋白酶抑制剂(PI)相比);含NRTI(与NRTI保留)。随机对照试验显示,转换为NRTI保留方案或从司他夫定/齐多夫定转换为阿巴卡韦/替诺福韦后,皮下脂肪增加。在各种治疗方案的随机对照试验中,躯干和/或内脏脂肪增加没有显著的组间差异,但依法韦仑与PI治疗方案的结果不一致。在从NRTI保留方案或含PI方案转换为NRTI保留方案或含PI方案的RCT中,中心脂肪增加无显著组间差异。有明确的证据表明NRTI(尤其是胸苷类似物)与脂肪萎缩之间存在因果关系,伴随使用的PI可能具有改善作用或依法韦仑导致累加毒性。相比之下,中枢脂肪增加似乎是治疗HIV感染的结果,因为它与对照组没有什么不同,与任何抗逆转录病毒药物无关,也没有改善转换。
Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART). Both are assumed to be antiretroviral adverse drug reactions. We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals. Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs) showed more limb fat loss (or less fat gain) with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs)); efavirenz (versus protease inhibitors (PIs)); and NRTI-containing (versus NRTI-sparing). RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens. There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues) and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.
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