在一项随机临床试验中，母亲在接受伐昔洛韦治疗并同时接受抗逆转录病毒 HIV-1 预防治疗期间和之后的婴儿安全性。
Infant safety during and after maternal valacyclovir therapy in conjunction with antiretroviral HIV-1 prophylaxis in a randomized clinical trial.
机构信息
Department of Global Health, University of Washington, Seattle, Washington, United States of America.
出版信息
PLoS One. 2012;7(4):e34635. doi: 10.1371/journal.pone.0034635. Epub 2012 Apr 11.
BACKGROUND
Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.
METHODS
Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm(3) were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher's Exact and Wilcoxon rank-sum tests were used for analysis.
RESULTS
One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6-4.19).
CONCLUSIONS
Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00530777.
背景
母体给予阿昔洛韦前体药物伐昔洛韦与妊娠和哺乳兼容。然而，在预防母婴 HIV-1 传播（PMTCT）的抗逆转录病毒（ARV）的背景下，婴儿和母亲长期暴露于阿昔洛韦的安全性尚未得到描述。
方法
在妊娠 34 周时，患有 HIV-1/HSV-2 合并感染且 CD4 计数 > 250 个细胞/mm(3)的肯尼亚孕妇被纳入研究，并随机分为每天两次口服 500mg 伐昔洛韦或安慰剂，直至产后 12 个月。从妊娠 28 周开始，所有孕妇均接受齐多夫定治疗，在分娩时为孕妇和婴儿单次给予奈韦拉平用于 PMTCT。在 6 周时，婴儿的血液样本用于肌酐和 ALT 检测。在伐昔洛韦组中，有 71 名女性在产后 2 周时采集了母乳样本；对 44 份（62%）随机样本进行了阿昔洛韦水平检测。使用 Fisher 精确检验和 Wilcoxon 秩和检验进行分析。
结果
共有 148 名女性被随机分组，146 对母婴在产后进行了随访。98%的婴儿和所有母亲均接受了 PMTCT ARV 治疗。伐昔洛韦与婴儿或母亲毒性或不良事件无关，也未观察到先天性畸形。婴儿的肌酐水平均正常（<0.83mg/dl），且研究组之间的婴儿生长情况没有差异。在产后 2 周采集的 44 份母乳样本中，有 35 份（80%）检测到阿昔洛韦。中位和最大阿昔洛韦浓度分别为 2.62 和 10.15mg/ml（四分位间距 0.6-4.19）。
结论
在 HIV-1/HSV-2 合并感染的女性中，在妊娠和产后期间给予母体伐昔洛韦后，婴儿和母亲暴露于 PMTCT ARV 和阿昔洛韦并不会增加婴儿或母亲的毒性或不良事件。
试验注册
ClinicalTrials.gov NCT00530777。
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