美国约翰霍普金斯大学Amita Gupta研究组的一项最新研究比较了对艾滋病病毒（HIV）感染孕妇和产妇进行异烟肼预防治疗的效果。该研究于2019年10月3日发表于国际一流学术期刊《新英格兰医学杂志》。

在这项多中心、双盲、安慰剂对照的非劣效性试验中，课题组对956名HIV感染孕妇进行异烟肼预防性治疗28周，随机分为妊娠期开始治疗（立即组，477名）和产后12周开始治疗（延后组，479名）。产后48周对母婴进行随访。

立即组中有72名女性发生治疗相关的3级以上不良反应或因毒副作用不得不永久终止试验，发生率为15.1%，延后组中有73例，发生率为15.2%，符合非劣效标准。立即组中有2名女性死亡，死亡率为每100人年0.40，延后组中有4名女性死亡，死亡率为每100人年0.78，死亡均发生在产后，其中4名死于肝衰竭。共有6名女性患肺结核，每组3例。直接组中综合妊娠不良结局（死产或自然流产、婴儿低出生体重、早产或婴儿先天畸形）的发生率为23.6%，高于延后组（17.0%）。

总之，怀孕期间开始进行异烟肼预防性治疗的风险似乎大于产后开始治疗的风险。

据悉，在接受抗逆转录病毒治疗的HIV感染妇女中，异烟肼疗法预防结核病的安全性、功效和适当时机仍尚未明确。

附：英文原文

Title: Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women

Author: Amita Gupta, Grace Montepiedra, Lisa Aaron, Gerhard Theron, Katie McCarthy, Sarah Bradford, Tsungai Chipato, Tichaona Vhembo, Lynda Stranix-Chibanda, Carolyne Onyango-Makumbi, Gaerolwe R. Masheto, Avy Violari, Blandina T. Mmbaga, Linda Aurpibul, Ramesh Bhosale, Vidya Mave, Vanessa Rouzier, Anneke Hesseling, Katherine Shin, Bonnie Zimmer, Diane Costello, Timothy R. Sterling, Nahida Chakhtoura, Patrick Jean-Philippe, Adriana Weinberg

Issue&Volume: Vol 381 No 14

Abstract: 

BACKGROUND
The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown.

METHODS
In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years.

RESULTS
A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], −4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, −0.39; 95% CI, −1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, −0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9).

CONCLUSIONS
The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. 

DOI: 10.1056/NEJMoa1813060

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1813060