替诺福韦富马酸替诺福酯未与肾脏损害相关(HIV)

StephenW

Tenofovir Disoproxil Fumarate Not Linked to Renal Damage
Zahra Masoud

Patients infected with HIV and receiving tenofovir disoproxil fumarate (TDF) as antiretroviral therapy (ART) have a greater risk for estimated glomerular filtration rate reduction if they have a lower body weight; however, this risk is not significant according to a study published in the Journal of Infection.

Current World Health Organization recommendations suggest using TDF as a part of initial ART for patients with HIV. TDF is also commonly used in combination for pre-exposure prophylaxis of HIV infection and monotherapy for the treatment of hepatitis B virus infection. Although the high potency of ART has dramatically improved survival of patients with HIV, chronic kidney disease remains one of the major comorbidities of HIV infection. The TDF regimen appears safe for short-term use in people with HIV, but has been associated with a broad spectrum of kidney tubular dysfunction.

Further, when combined with a boosted protease inhibitor, TDF is associated with a higher risk for estimated glomerular filtration rate reduction, which could increase the long-term risk for chronic kidney disease. However, the risk for eGFR reduction in Asian adults with HIV who initiate ART containing TDF remains unclear. Therefore, this study compared the long-term evolution of estimated glomerular filtration rate in Thai patients receiving TDF and zidovudine (AZT) and analyzed the role of body weight in the risk for estimated glomerular filtration rate reduction.

In total, data collected from a multicenter clinical trial in Thailand of 640 patients were included (ClinicalTrials.gov identifier: NCT00162682). Of these included patients, 461 (72%) patients received a TDF-containing regimen for a median of 6.7 years, and 179 (28%) patients received an AZT-containing regimen for 6.5 years. The estimated glomerular filtration rate was estimated for each patient before initiation of ART, and quarterly thereafter. The primary outcome measure was the time to >25% reduction in estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease equation with Thai racial factor during the follow-up period. Using proportional hazard regression models, the risk for a >25% estimated glomerular filtration rate reduction in HIV-naive patients initiating TDF of AZT-containing nonprotease inhibitor regimen were compared.

Results showed that the risk for a >25% estimated glomerular filtration rate reduction was not higher on TDF-based vs AZT-based nonprotease inhibitor regimens, and therefore was not associated with treatment (hazard ratio [HR], 1.11; P =.46). Multivariate analysis showed that the risk for >25% estimated glomerular filtration rate reduction from baseline was associated with body weight at baseline (HR, 2.12; P <.001); this was also true for patients with hypertension (HR, 4.03; P <.001). However, the effect on baseline weight on >25% estimated glomerular filtration rate reduction did not vary significantly with treatment (P =.27).
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Overall, the study authors concluded that, “HIV infected-patients initiating TDF-containing antiretroviral combinations without protease inhibitors did not have a higher risk of [estimated glomerular filtration rate] reduction or [chronic kidney disease] compared with AZT containing regimens in Thailand.”

Reference

Liegeon G, Harrison L, Nechba A, et al. Long term renal function in Asian HIV-1 infected adults receiving tenofovir disoproxil fumarate without protease inhibitors [published online August 8, 2019]. J Infect. doi:10.1016/j.jinf/2019.08.006

StephenW

替诺福韦富马酸替诺福酯未与肾脏损害相关
扎赫拉·马苏德（Zahra Masoud）

感染艾滋病毒且接受替诺福韦富马酸替诺福韦（TDF）作为抗逆转录病毒疗法（ART）的患者，如果体重较轻，则估计肾小球滤过率降低的风险更大；但是，根据《感染杂志》上发表的一项研究，这种风险并不明显。

世界卫生组织当前的建议建议将TDF用作HIV患者初始抗病毒治疗的一部分。 TDF还通常与HIV的暴露前预防和乙型肝炎病毒感染的单一疗法结合使用。尽管抗逆转录病毒疗法的高效力极大地提高了艾滋病毒患者的生存率，但慢性肾脏疾病仍然是艾滋病毒感染的主要合并症之一。 TDF方案对于HIV感染者短期使用似乎是安全的，但与广泛的肾小管功能障碍有关。

此外，当与强化的蛋白酶抑制剂联合使用时，TDF与估计的肾小球滤过率降低的较高风险相关，这可能会增加慢性肾脏疾病的长期风险。然而，在亚洲艾滋病毒感染者中开始含有TDF的抗逆转录病毒疗法降低eGFR的风险尚不清楚。因此，本研究比较了泰国接受TDF和齐多夫定（AZT）的患者估计肾小球滤过率的长期演变，并分析了体重在估计肾小球滤过率降低风险中的作用。

总共包括在泰国的一项多中心临床试验中收集的640名患者的数据（ClinicalTrials.gov标识符：NCT00162682）。在这些患者中，有461名（72％）患者接受了含TDF方案，中位数为6.7年，而179名（28％）患者接受了含AZT方案，为期6.5年。在开始抗逆转录病毒治疗之前和之后每季度评估每个患者的估计的肾小球滤过率。主要结局指标是在随访期间，通过采用泰国种族因素进行的“肾脏疾病饮食中饮食的修正”方程评估的估计肾小球滤过率降低> 25％的时间。使用比例风险回归模型，比较了初次使用含AZT的非蛋白酶抑制剂方案的TDF的HIV初治患者估计肾小球滤过率降低> 25％的风险。

结果显示，与基于AZT的非蛋白酶抑制剂相比，基于TDF的肾小球滤过率降低> 25％的风险并不更高，因此与治疗无关（危险比[HR]，1.11； P = .46 ）。多变量分析显示，估计的肾小球滤过率从基线降低> 25％的风险与基线时的体重相关（HR，2.12； P <.001）；与基线时的体重相关。高血压患者也是如此（HR，4.03； P <.001）。但是，估计基​​线重量> 25％的肾小球滤过率降低对治疗的影响并没有显着变化（P = .27）。
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总体而言，研究作者得出结论：“与泰国的AZT疗法相比，在没有蛋白酶抑制剂的情况下发起含TDF的抗逆转录病毒组合的HIV感染患者没有[估计的肾小球滤过率]降低或[慢性肾脏疾病]更高的风险。 ”

参考

Liegeon G，Harrison L，Nechba A等。接受富马酸替诺福韦酯而不加蛋白酶抑制剂的亚洲HIV-1感染成年人的长期肾功能[2019年8月8日在线发布]。 J感染。 DOI：10.1016 / j.jinf / 2019.08.006