评价包含替诺福韦的联合抗逆转录病毒疗法对 HIV 感染患者的肾脏不良影响。

Evaluation of renal adverse effects of combination anti-retroviral therapy including tenofovir in HIV-infected patients.

机构信息

Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-ku, Sagamihara-city, Kanagawa, 252-0375.

出版信息

J Pharm Pharm Sci. 2013;16(3):405-13. doi: 10.18433/j32p5c.

DOI:10.18433/j32p5c

PMID:24021289

Abstract

PURPOSE

In order to maintain plasma HIV-RNA concentration in HIV-infected patients, below the detection limit combination anti-retroviral therapy (cART) are used. Although the nucleoside/nucleotide reverse transcriptase inhibitor, tenofovir disoproxil fumarate (TDF) is a first-line drug commonly used, it is associated with renal dysfunction. Nevertheless, only few clinical studies have focused on TDF in combination with new anti-HIV drugs, including the protease inhibitor (PI) darunavir (DRV), or the integrase strand transfer inhibitor (INSTI) raltegravir (RAL). Here we report the influence of such cART involving TDF on renal function.

METHODS

We retrospectively investigated 68 patients under cART that included TDF between November 2004 and May 2012. We used hospital records to establish each patient's background and characteristics, CD4 cell count, plasma HIV-RNA concentration, drug combinations, renal function, and anti-retrovial therapy history.

RESULTS

In all patients who had received cART, the plasma HIV-RNA concentration had fallen to less than 40 copies/mL by week 24 after the start of the therapy, and an increase in the CD4 cell count was observed. For each drug used in combination with TDF, the plasma HIV-RNA concentration and CD4 cell count showed a similar trend. After week 12, the estimated glomerular filtration rate (eGFR) had significantly decreased in all patients. The eGFR was significantly lower in those received PI on week 24 and in those received INSTI on week 12. The eGFR was significantly reduced in PI group who received atazanavir + ritonavir (ATV/RTV) on week 60. The eGFR in the DRV/RTV group tended to decrease. The eGFR in the PI and ATV/RTV group was significantly lower than in the efavirenz (EFV) group on week 96.

CONCLUSION

It selecting drugs to include in combination therapy of HIV-infected patients, consideration should be given to the risk of renal dysfunction. There is a need to monitor renal function when TDF is combined with ATV/RTV, DRV/RTV or RAL.

摘要

目的

为了维持感染 HIV 的患者的血浆 HIV-RNA 浓度在检测下限以下，使用了联合抗逆转录病毒疗法（cART）。尽管核苷酸逆转录酶抑制剂富马酸替诺福韦二吡呋酯（TDF）是常用的一线药物，但它与肾功能障碍有关。然而，只有少数临床研究集中在 TDF 与新的抗 HIV 药物联合使用上，包括蛋白酶抑制剂（PI）达芦那韦（DRV）或整合酶链转移抑制剂（INSTI）拉替拉韦（RAL）。在这里，我们报告了包含 TDF 的这种 cART 对肾功能的影响。

方法

我们回顾性调查了 2004 年 11 月至 2012 年 5 月期间接受包含 TDF 的 cART 的 68 名患者。我们使用医院记录来建立每位患者的背景和特征、CD4 细胞计数、血浆 HIV-RNA 浓度、药物组合、肾功能和抗逆转录病毒治疗史。

结果

所有接受 cART 的患者在治疗开始后 24 周内血浆 HIV-RNA 浓度降至低于 40 拷贝/mL，并且观察到 CD4 细胞计数增加。对于与 TDF 联合使用的每种药物，血浆 HIV-RNA 浓度和 CD4 细胞计数均表现出相似的趋势。在第 12 周后，所有患者的估算肾小球滤过率（eGFR）均显著下降。在第 24 周接受 PI 的患者和在第 12 周接受 INSTI 的患者的 eGFR 显著降低。在第 60 周接受阿扎那韦+利托那韦（ATV/RTV）的 PI 组的 eGFR 显著降低。DRV/RTV 组的 eGFR 有下降的趋势。在第 96 周，PI 和 ATV/RTV 组的 eGFR 明显低于 EFV 组。