抗逆转录病毒治疗起始时蛋白尿和白蛋白尿的变化：来自一项比较替诺福韦二吡呋酯/恩曲他滨与阿巴卡韦/拉米夫定的随机试验的数据。
Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine.
机构信息
*Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; §Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA; ‖Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; ¶ViiV Healthcare, Research Triangle Park, NC; #Gilead Sciences, Foster City, CA; and **Department of Pediatrics, Case Western Reserve University, Cleveland, OH.
出版信息
J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):36-44. doi: 10.1097/QAI.0000000000000245.
BACKGROUND
Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria.
METHODS
We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz.
RESULTS
At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥200 mg/g), and 11% had clinically significant albuminuria (UACR ≥30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR (P = 0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant interactions between NRTI and NNRTI/PI components.
CONCLUSIONS
In this prespecified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings.
背景
抗逆转录病毒疗法（ART）可改善肾功能；然而，核苷酸逆转录酶抑制剂（NRTI）替诺福韦二吡呋酯（TDF）与肾功能下降和蛋白尿有关。
方法
我们在 A5202 研究中检查了 245 名接受 ART 治疗的初治参与者的尿液蛋白：肌酐（UPCR）和尿液白蛋白：肌酐（UACR）比值的变化情况，这些参与者被随机分为亚组接受盲法 NRTI（阿巴卡韦/拉米夫定，ABC/3TC，n = 124 或 TDF/恩曲他滨，TDF/FTC，n = 121）联合开放标签蛋白酶抑制剂（PI）阿扎那韦/利托那韦或非核苷类逆转录酶抑制剂（NNRTI）依非韦伦。
结果
基线时，18%的参与者有临床显著蛋白尿（UPCR≥200mg/g），11%有临床显著白蛋白尿（UACR≥30mg/g）。所有治疗组的临床显著蛋白尿和白蛋白尿的患病率从基线到 96 周时均下降。在意向治疗分析中，NRTI 成分对 UPCR（P=0.011）和 UACR（P=0.018）从基线到 96 周的变化的影响有统计学意义，与随机分配到 ABC/3TC 的参与者相比，有显著改善。NNRTI/PI 成分对 UPCR（P=0.23）或 UACR（P=0.88）的变化没有显著影响，NRTI 和 NNRTI/PI 成分之间也没有显著的相互作用。
结论
在这个预先指定的二次分析中，ART 启动与蛋白尿和白蛋白尿的改善相关，与随机分配到 ABC/3TC 组的参与者相比，TDF/FTC 组的改善更为显著。这些是来自随机试验的第一批数据，表明与其他方案报道的改善程度相比，TDF/FTC 的启动可能不会导致同样程度的蛋白尿和白蛋白尿改善。未来的研究应考虑这些发现的长期临床意义。
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