Osorio Luiz Eduardo, Boechat Maria Ines, Mirochnick Mark, Kumwenda Newton, Kreitchmann Regis, Emel Lynda, Pinto Jorge, Joao Esau, Santos Breno, Swenson Molly, George Kathleen, Sato Paul, Mofenson Lynne, Nielsen-Saines Karin
From the *Department of Pediatrics, David Geffen UCLA School of Medicine, Los Angeles, California; †Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts; ‡Department of Medicine, Malawi College of Medicine, Blantyre, Malawi; §Department of Obstetrics and Gynecology, Santa Casa de Misericordia, Porto Alegre, Brazil; ¶SCHARP Fred Hutchinson Cancer Research Center, Seattle, Washington; ‖Department of Pediatrics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; **Department of Infectious Diseases, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil; ††Department of Infectious Diseases, Hospital Conceicao, Porto Alegre, Brazil; ‡‡Family Health International, Durham, North Carolina; §§National Institute of Allergy and Infectious Diseases, and ¶¶Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Pediatr Infect Dis J. 2017 Feb;36(2):184-188. doi: 10.1097/INF.0000000000001386.
Tenofovir disoproxil fumarate (TDF) use during pregnancy has been increasing, and studies linking bone toxicity with exposure to TDF have raised concern for its use in infants.
Hand/wrist and spine radiographs were obtained at 3 days and 12 weeks of age in infants born to HIV-infected pregnant women enrolled in the HIV Prevention Trials Network 057 pharmacokinetic study of TDF conducted in Malawi and Brazil assigned to 3 TDF dosing cohorts. In cohort 1, mothers received 600 mg of TDF during labor. In cohort 2, infants received 4 mg/kg dose on days 0, 3 and 5. In cohort 3, a 900 mg maternal dose was given during labor, followed by a 6 mg/kg infant dose on days 0, 3 and 5 of life.
Across all 3 cohorts, 89 infants had radiographs performed at either time point, and 85 had radiographs performed at both time points. Metaphyseal lucency was present in 1 case in Brazil and 2 in Malawi. Fifteen percent of infants from Brazil and 9% of infants from Malawi presented bone age discrepancies. No other abnormalities were identified in Brazil, whereas in Malawi, there were 7 more cases of wrist osteopenia, 2 of spine osteopenia and 3 other abnormalities.
Bone abnormalities were not uncommon in the overall cohort of HIV-exposed infants. Because of very limited study drug exposure at the time of birth, it is unlikely that TDF was associated with these findings. Untreated maternal HIV disease and/or maternal nutritional status could potentially be related to fetal bone development. This association should be explored in future cohort studies.
孕期使用替诺福韦酯（TDF）的情况一直在增加，而将骨毒性与TDF暴露联系起来的研究引发了对其在婴儿中使用的担忧。
在马拉维和巴西进行的HIV预防试验网络057关于TDF的药代动力学研究中，对感染HIV的孕妇所生婴儿在3日龄和12周龄时进行手部/腕部及脊柱X光检查，这些婴儿被分配到3个TDF给药队列。在队列1中，母亲在分娩时接受600毫克TDF。在队列2中，婴儿在第0、3和5天接受4毫克/千克剂量。在队列3中，母亲在分娩时给予900毫克剂量，随后婴儿在出生后第0、3和5天接受6毫克/千克剂量。
在所有3个队列中，89名婴儿在两个时间点中的任一时刻进行了X光检查，85名婴儿在两个时间点都进行了X光检查。在巴西有1例、马拉维有2例出现干骺端透亮。巴西15%的婴儿和马拉维9%的婴儿存在骨龄差异。在巴西未发现其他异常，而在马拉维，腕部骨质减少多了7例，脊柱骨质减少多了2例，还有3例其他异常。
在总体暴露于HIV的婴儿队列中，骨骼异常并不罕见。由于出生时研究药物暴露非常有限，TDF不太可能与这些发现相关。未治疗的母亲HIV疾病和/或母亲营养状况可能与胎儿骨骼发育有关。这种关联应在未来的队列研究中进行探索。
