Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, 651 Huntington Avenue, Boston, MA, 02115, USA.
College of Medicine, University of Malawi, Blantyre, Malawi.
BMC Infect Dis. 2022 Jul 20;22(1):634. doi: 10.1186/s12879-022-07608-8.
Tenofovir disoproxil fumarate (TDF) in combination with other antiretroviral (ARV) drugs has been in clinical use for HIV treatment since its approval in 2001. Although the effectiveness of TDF in preventing perinatal HIV infection is well established, information about renal safety during pregnancy is still limited.
The IMPAACT PROMISE study was an open-label, strategy trial that randomized pregnant women to one of three arms: TDF based antiretroviral therapy (ART), zidovudine (ZDV) based ART, and ZDV alone (standard of care at start of enrollment). The P1084s substudy was a nested, comparative study of renal outcomes in women and their infants.
PROMISE participants (n = 3543) were assessed for renal dysfunction using calculated creatinine clearance (CrCl) at study entry (> 14 weeks gestation), delivery, and postpartum weeks 6, 26, and 74. Of these women, 479 were enrolled in the P1084s substudy that also assessed maternal calcium and phosphate as well as infant calculated CrCl, calcium, and phosphate at birth.
Among the 1338 women who could be randomized to TDF, less than 1% had a baseline calculated CrCl below 80 mL/min. The mean (standard deviation) maternal calculated CrCl at delivery in the TDF-ART arm [147.0 mL/min (51.4)] was lower than the ZDV-ART [155.0 mL/min (43.3); primary comparison] and the ZDV Alone [158.5 mL/min (45.0)] arms; the mean differences (95% confidence interval) were - 8.0 mL/min (- 14.5, - 1.5) and - 11.5 mL/min (- 18.0, - 4.9), respectively. The TDF-ART arm had lower mean maternal phosphate at delivery compared with the ZDV-ART [- 0.14 mg/dL (- 0.28, - 0.01)] and the ZDV Alone [- 0.17 mg/dL (- 0.31, - 0.02)] arms, and a greater percentage of maternal hypophosphatemia at delivery (4.23%) compared with the ZDV-ART (1.38%) and the ZDV Alone (1.46%) arms. Maternal calcium was similar between arms. In infants, mean calculated CrCl, calcium, and phosphate at birth were similar between arms (all CIs included 0).
Although mean maternal calculated CrCl at Delivery was lower in the TDF-ART arm, the difference between arms is unlikely to be clinically significant. During pregnancy, the TDF-ART regimen had no observed safety concerns for maternal or infant renal function.
NCT01061151 on 10/02/2010 for PROMISE (1077BF). NCT01066858 on 10/02/2010 for P1084s.
富马酸替诺福韦二吡呋酯（TDF）自 2001 年获得批准用于治疗 HIV 以来，一直与其他抗逆转录病毒（ARV）药物联合用于临床治疗。虽然 TDF 预防围产期 HIV 感染的有效性已得到充分证实，但关于妊娠期间肾脏安全性的信息仍然有限。
IMPACT PROMISE 研究是一项开放性标签、策略性试验，将孕妇随机分配到以下三个治疗组之一：基于 TDF 的抗逆转录病毒治疗（ART）、齐多夫定（ZDV）为基础的 ART 和 ZDV 单药治疗（入组时的标准治疗）。P1084s 子研究是一项嵌套的比较性研究，评估了女性及其婴儿的肾脏结局。
PROMISE 参与者（n=3543）在研究入组时（妊娠>14 周）、分娩时和产后第 6、26 和 74 周时使用计算的肌酐清除率（CrCl）评估肾功能障碍。这些女性中有 479 名参加了 P1084s 子研究，该研究还评估了产妇的钙和磷酸盐以及婴儿出生时的计算 CrCl、钙和磷酸盐。
在 1338 名可随机分配至 TDF 的女性中，不到 1%的女性基线计算 CrCl 低于 80mL/min。TDF-ART 组的产妇分娩时平均（标准差）计算 CrCl [147.0mL/min（51.4）]低于 ZDV-ART [155.0mL/min（43.3）；主要比较]和 ZDV 单药治疗组 [158.5mL/min（45.0）]；平均差异（95%置信区间）分别为-8.0mL/min（-14.5，-1.5）和-11.5mL/min（-18.0，-4.9）。TDF-ART 组产妇分娩时的平均磷酸盐水平低于 ZDV-ART 组[-0.14mg/dL（-0.28，-0.01）]和 ZDV 单药治疗组[-0.17mg/dL（-0.31，-0.02）]，并且分娩时发生低磷酸盐血症的产妇比例更高（4.23%比 ZDV-ART 组的 1.38%和 ZDV 单药治疗组的 1.46%）。产妇的钙水平在各组间相似。在婴儿中，出生时的平均计算 CrCl、钙和磷酸盐在各组间相似（所有 CI 均包含 0）。
尽管 TDF-ART 组产妇分娩时的平均计算 CrCl 较低，但两组间的差异不太可能具有临床意义。在妊娠期间，TDF-ART 方案对母婴肾功能没有观察到安全问题。
NCT01061151 于 2010 年 10 月 2 日用于 PROMISE（1077BF）。NCT01066858 于 2010 年 10 月 2 日用于 P1084s。
