Protease inhibitor use during pregnancy: is there an obstetrical risk?
Protease inhibitor use during pregnancy: is there an obstetrical risk?
复制标题
怀孕期间使用蛋白酶抑制剂：是否存在产科风险？
DOI：
10.1086/503049
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Yawetz,Sigal
中科院分区：
文献类型：
--
作者：
Tuomala,RuthE;Yawetz,Sigal
The reduction in the rate of vertical transmission of HIV-1 from an infected woman to her neonate through the use of antiretroviral agents is one of the success stories of the AIDS era. The use of combination antiretroviral therapy (ART) is particularly effective, with resultant rates of vertical transmission of! 2%[1, 2]. This success has led to widespread use during pregnancy of multiple medications for which adverse maternal, pregnancy, and fetal/neonatal outcomes are incompletely known. Potential risks have been accepted because of the compelling benefit that has been demonstrated through multiple controlled clinical trials and observational studies. Adverse outcomes associated with the use of combination ART during pregnancy have been assessed through the analysis of observational or clinical databases collected using a variety of methods, often across eras of varying HIV management and in accordance with varying standards of scientific rigor. Analyses have yielded inconsistent results with respect to pregnancy outcomes. In particular, whether or not combination ART, most specifically that including protease inhibitors (PIs), is associated with an excess of preterm deliveries is in question. In general, analyses of data from European cohorts [3–6] have demonstrated an association between preterm delivery and combination ART, but similar analyses from the United States and France have shown no association [2, 7–9] or, in some cases, a beneficial effect. A summary of the findings relative to preterm delivery from these studies is provided in table 1. The study by Cotter et al.[10] in this issue of the Journal of Infectious Diseases is, to our knowledge, the first analysis from the United States to associate combination ART that includes a PI with preterm delivery (at! 37 weeks of gestation). The authors used prospectively collected data from a database collected over the course of 12 years at a single site, using standardized management protocols to assess pregnancy outcomes in HIV-infected women. Using pairwise comparisons similar to those used in the US combined-cohorts study, after adjustment for multiple risk factors for preterm delivery, the authors found that ART including a PI was associated with an increased risk of preterm delivery, compared with both other combination ART (adjusted odd ratio [AOR], 1.8) and all other study patients (AOR, 2.3). Exposure to a PI for 110 weeks increased the risk of preterm delivery. Subgroup analysis according to 3 time periods based on evolving standards of care showed trends toward an increased risk of preterm delivery associated with PI use during the 3 time periods, although findings were only significant for the earliest period, between 1995 and 1997. Discrepant results have been ascribed to inherent differences in patient populations, differences between providers in choice of ART and the use of elective cesarean section, and differences in the ascertainment of study populations and in the exact data analyzed. Of note, the European Collaborative and Swiss Cohort Studies analysis and the subsequent reports from the European Collaborative Study (ECS) did not control for prior preterm delivery, a major risk factor for premature delivery. This factor was included in the analyses of the US combined cohorts study, the Women and Infants Transmission Study (WITS), and the study by Cotter et al. The ECS controlled for the duration of PI use, which the US combined cohort study did not. Although CD4+ cell counts were taken into account, earlier reports did not con-
