Division of Pediatric Infectious Disease, BronxCare Health System, Icahn School of Medicine at Mount Sinai, Bronx, New York, USA.
Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA.
J Pediatric Infect Dis Soc. 2024 Aug 24;13(8):396-405. doi: 10.1093/jpids/piae054.
Tenofovir disoproxil fumarate (TDF) is often used in treating pregnant women living with HIV. Third-trimester TDF exposure is associated with a 12% reduction in bone mineral content in HIV-exposed uninfected (HEU) neonates. The potential mechanisms underlying this observation are unknown.
The TDF study enrolled newborns of gestational age ≥36 weeks from the Surveillance Monitoring for Antiretroviral Therapy and Toxicities study based on in utero TDF exposure (TDF use ≥8 weeks in the third trimester vs none). Blood and urine samples were collected cross-sectionally within 30 days of birth to assess renal function (serum creatinine, serum phosphate, eGFR, percent tubular reabsorption of phosphate [PTRP]), and bone turnover (serum parathyroid hormone, 25-OH vitamin D [25(OH)D], and urinary cross-linked N-telopeptide of type 1 collagen). For each biomarker, a LOESS plot was fit using values at age at specimen collection; regression lines over age were fit among samples collected from 4 to 30 days, to compare slopes by TDF exposure.
Among 141 neonates, 77 were TDF-exposed and 64 TDF-unexposed. Between age 4 and 30 days, PTRP decreased more rapidly in the TDF-exposed compared to the unexposed group with slopes of -0.58 vs -0.08/day (difference -0.50/day [95% CI -0.88, -0.11]). Slopes for 25(OH)D were similar in both groups, but serum levels were lower in TDF-exposed neonates (median [IQR]: 22 [19, 29] vs 26 [22, 37] ng/mL). No differences were observed for other biomarkers.
Third-trimester in utero exposure to TDF is associated with increased urinary loss of phosphate and lower serum concentrations of 25(OH)D in HEU neonates.
富马酸替诺福韦二吡呋酯（TDF）常用于治疗感染 HIV 的孕妇。在 HIV 暴露但未感染（HEU）的新生儿中，第三孕期 TDF 暴露与骨矿物质含量降低 12%相关。导致这一观察结果的潜在机制尚不清楚。
TDF 研究纳入了来自监测抗逆转录病毒治疗和毒性研究的胎龄≥36 周的新生儿，这些新生儿基于宫内 TDF 暴露（第三孕期 TDF 使用≥8 周与无 TDF 使用）。在出生后 30 天内采集血样和尿样，以评估肾功能（血清肌酐、血清磷酸盐、eGFR、尿磷酸盐重吸收率[PTRP]%）和骨转换（血清甲状旁腺激素、25-羟维生素 D[25(OH)D]和尿 1 型胶原交联 N-末端肽）。对于每个生物标志物，使用采集标本时的年龄值拟合 LOESS 图；在 4 至 30 天采集的样本中拟合回归线，以比较 TDF 暴露组的斜率。
在 141 名新生儿中，77 名接受 TDF 暴露，64 名未接受 TDF 暴露。在 4 至 30 天期间，TDF 暴露组 PTRP 下降速度快于未暴露组，斜率分别为-0.58 与-0.08/天（差异为-0.50/天[95%CI -0.88，-0.11]）。两组的 25(OH)D 斜率相似，但 TDF 暴露组新生儿血清水平较低（中位数[IQR]：22[19，29]与 26[22，37]ng/ml）。其他生物标志物未见差异。
第三孕期宫内 TDF 暴露与 HEU 新生儿磷酸盐尿丢失增加和血清 25(OH)D 浓度降低相关。
