TDF-to-TAF切换后肾功能的变化：谁最受益？

StephenW

[email protected]
       
Change in Kidney Function After TDF-to-TAF Switch: Who Benefits Most?

10th IAS Conference on HIV Science (IAS 2019), July 21-24, 2019, Mexico City

Mark Mascolini

Kidney function assessed by estimated glomerular filtration rate (eGFR) did not differ through 18 months in Swiss HIV patients who stayed with tenofovir disoproxil fumarate (TDF) or switched to tenofovir alafenamide (TAF)--if those people had normal kidney function at the switch [1]. But this 3520-person Swiss HIV Cohort Study (SHCS) analysis found markedly improved kidney function after the switch to TAF in people with established poor kidney function, whereas kidney function continued to decline when people with poor function stayed with TDF. The study also found that improving eGFR may be less likely in people taking a boosted protease inhibitor (PI) at the switch.

TAF trials confirmed improving kidney function markers in people switching from TDF. SHCS investigators undertook this analysis to learn how kidney function changed in the clinic when HIV patients switched to TAF versus staying with TDF. For this analysis they assessed kidney function as eGFR and protein-to-creatinine ratio.

The SHCS team included cohort members in this analysis if they (1) took TDF and continued taking it to the end of the observation period (March 2019) or (2) took TDF, switched to TAF, and remained on TAF. Participants needed 2 or more creatinine measurements before and after the baseline date, defined as the day a person switched to TAF (in the TAF group) or October 1, 2016 (in the TDF group).

Among 8399 SHCS members who ever took TDF, 3520 met study entry criteria, of whom 1113 (32%) stayed with TDF and 2407 (68%) switched to TAF. The TAF and TDF groups had median ages of 51 and 48 years and median CD4 counts of 646 and 628. Proportions of women were 24% with TAF and 32% with TDF, Africans 13% with TAF and 20% with TDF, and people who inject drugs 11% with TAF and 9% with TDF. Comorbidity rates were similar with TAF and TDF for diabetes (8% and 6%), cardiovascular disease (9% and 7%), HCV infection (13% and 13%), and HBV infection (7% and 8%). The TAF group had a higher proportion with osteoporosis (7% versus 3%).

Baseline eGFR was worse in the TAF group than the TDF group: 7% versus 2% below 60 mL/min, and 45% versus 35% at 60 to 89 mL/min. Among people with a normal baseline eGFR (at or above 90 mL/min), eGFR through 18 months of follow-up dropped at the same rate in the TAF and TDF group, 1.7 mL/min in an analysis adjusted for age, sex, ethnicity, diabetes, hypertension, cardiovascular disease, HCV or HBV infection, and use of ritonavir, cobicistat, dolutegravir, or cotrimoxazole.

In the same type of analysis, through 18 months of follow-up in people with a baseline eGFR between 60 and 89 mL/min, eGFR rose 1.5 mL/min in the TAF group while falling 0.9 mL/min in the continued-TDF group. And in people with a baseline eGFR below 60 mL/min, eGFR rose 4.1 mL/min through 18 months in the TAF group while falling 5.8 mL/min in the TDF group.

Regression analysis in people who switched to TAF with a baseline eGFR below 90 mL/min independently linked every 10 years of age to a lower likelihood of rising eGFR, while chronic HCV infection tended to predict a greater likelihood of rising eGFR in TAF patients. Among TAF switchers with a baseline eGFR below 60 mL/min, only taking a boosted PI at baseline predicted a lower likelihood of increasing eGFR. Again, chronic HCV infection tended to predict a greater likelihood of increasing eGFR.

Through 18 months of follow-up, protein-to-creatinine ratio rose 2.6 mg/mmol in the continued-TDF group while falling 5.2 mg/mmol in the TAF group.

Cautioning that longer follow-up must confirm these results, the SHCS team concluded that eGFR improved through 18 months in people with established kidney dysfunction switching from TDF to TAF but remained similar after the switch in people with normal kidney function.

Reference
1. Surial B, Ledergerber B, Calmy A, et al. Renal function trajectories after switching from TDF to TAF: A nationwide cohort study. 10th IAS Conference on HIV Science (IAS 2019), July 21-24, 2019, Mexico City. Abstract MOAB0205.

StephenW

[email protected]

TDF-to-TAF切换后肾功能的变化：谁最受益？

第10届IAS艾滋病科学会议（IAS 2019），墨西哥城，2019年7月21日至24日

马克马斯科利尼

通过估计肾小球滤过率（eGFR）评估的肾功能在瑞士HIV患者中持续18个月没有差异，他们使用替诺福韦地索普西富马酸盐（TDF）或改用替诺福韦艾拉酚胺（TAF） - 如果那些人在开关时肾功能正常[1]。但这项3520人的瑞士艾滋病毒队列研究（SHCS）分析显示，在肾功能确定不良的人群中转为TAF后，肾功能明显改善，但功能不良的人继续使用TDF时肾功能继续下降。该研究还发现，在转换时服用增强蛋白酶抑制剂（PI）的人群中，改善eGFR的可能性较小。

TAF试验证实改善TDF患者的肾功能指标。 SHCS研究人员进行了这项分析，以了解当HIV患者转为TAF而不是继续使用TDF时，临床上肾功能如何发生变化。对于该分析，他们评估肾功能为eGFR和蛋白质 - 肌酸酐比率。

SHCS团队在此分析中包括队列成员，如果他们（1）采用TDF并继续将其带到观察期结束（2019年3月）或（2）采用TDF，切换到TAF，并保持TAF。参与者在基线日期之前和之后需要2次或更多次肌酐测量，定义为一个人切换到TAF（在TAF组中）或2016年10月1日（在TDF组中）的日期。

在曾参加过TDF的8399名SHCS成员中，3520人符合入学标准，其中1113人（32％）留在TDF，2407人（68％）转为TAF。 TAF和TDF组的中位年龄分别为51岁和48岁，中位CD4计数分别为646和628.女性比例为24％，TAF为32％，TDF为32％，非洲人为13％，TAF为20％，TDF为20％。用TAF注射药物11％，用TDF注射9％。合并症发生率与糖尿病（8％和6％），心血管疾病（9％和7％），HCV感染（13％和13％）和HBV感染（7％和8％）的TAF和TDF相似。 TAF组患骨质疏松症的比例较高（7％对3％）。

TAF组的基线eGFR比TDF组更差：7％对比低于60 mL / min的2％，45％对比35％，60至89 mL / min。在基线eGFR正常（达到或高于90 mL / min）的患者中，经过18个月随访的eGFR在TAF和TDF组中以相同的速率下降，1.7 mL / min的分析调整了年龄，性别，种族，糖尿病，心血管疾病，HCV或HBV感染，以及利托那韦，cobicistat，dolutegravir或复方新诺明的使用。

在同一类型的分析中，对于基线eGFR在60和89 mL / min之间的18个月随访，TAF组的eGFR上升1.5 mL / min，而持续TDF组的下降为0.9 mL / min对于基线eGFR低于60 mL / min的患者，TAF组eGFR升高4.1 mL / min至18个月，TDF组降低5.8 mL / min。

在转换为TAF且基线eGFR低于90 mL / min的人群中，每10岁时接触的eGFR升高的可能性较低，而慢性HCV感染倾向于预测TAF患者中eGFR升高的可能性更大。基线eGFR低于60 mL / min的TAF切换器仅在基线时采用增强PI，预测eGFR增加的可能性较低。同样，慢性HCV感染倾向于预测增加eGFR的可能性更大。

通过18个月的随访，持续TDF组蛋白质与肌酐比率上升2.6 mg / mmol，TAF组下降5.2 mg / mmol。

最后一次随访的注意事项必须证实这些结果，SHCS团队得出结论，在患有肾功能不全的患者中，从TDF转为TAF，eGFR改善了18个月，但在肾功能正常的患者转换后仍然相似。

参考
1. Surial B，Ledergerber B，Calmy A，et al。从TDF转换为TAF后的肾功能轨迹：全国范围的队列研究。第10届IAS艾滋病科学会议（IAS 2019），墨西哥城，2019年7月21日至24日。摘要MOAB0205。