在博茨瓦纳的 Mma Bana 研究中，高病毒载量和升高的血管生成标志物与开始高活性抗逆转录病毒治疗的孕妇中先兆子痫风险增加相关。
High viral load and elevated angiogenic markers associated with increased risk of preeclampsia among women initiating highly active antiretroviral therapy in pregnancy in the Mma Bana study, Botswana.
机构信息
Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
出版信息
J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):517-24. doi: 10.1097/QAI.0b013e318286d77e.
BACKGROUND
Risk factors associated with preeclampsia in HIV-infected women remain largely unknown. Systemic angiogenic imbalance contributes to preeclampsia in HIV-uninfected women, but changes in angiogenic markers after highly active antiretroviral therapy (HAART) initiation have not been studied.
METHODS
The Mma Bana study randomized 560 HIV-infected, HAART-naive pregnant women with CD4 counts ≥ 200 cells per cubic millimeter between 26 and 34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine or abacavir/zidovudine/lamivudine. Another 170 participants with CD4 counts less than 200 cells per cubic millimeter initiated nevirapine/zidovudine/lamivudine between 18 and 34 weeks gestation. Characteristics of 11 women who developed preeclampsia were compared with the remaining 722 Mma Bana participants who delivered using logistic regression. Plasma samples drawn at HAART initiation and 1 month later from 60 women without preeclampsia and at HAART initiation for all 11 preeclamptic women were assayed for placental growth factor (PlGF) and soluble FMS toll-like tyrosine kinase-1 (sFlt-1).
RESULTS
Pre-HAART viral load greater than 100,000 copies per milliliter was associated with preeclampsia (odds ratio: 5.8, 95% confidence interval: 1.8 to 19.4, P = 0.004). Median pre-HAART PlGF level was lower and sFlt-1 was higher in women who developed preeclampsia vs those who did not (130 vs 992 pg/mL, P = 0.001; 17.5 vs 9.4 pg/mL, P = 0.03, respectively). In multivariate analysis, PlGF and viral load remained significantly associated with preeclampsia. No significant changes in angiogenic factors were noted after 1 month of HAART treatment among non-preeclamptic women.
CONCLUSIONS
Pre-HAART viral load greater than 100,000 copies per milliliter and PlGF predicted preeclampsia among women starting HAART in pregnancy. Among non-preeclamptic women, HAART treatment did not significantly alter levels of PlGF or sFlt-1 after 1 month of treatment.
背景
与 HIV 感染妇女子痫前期相关的风险因素在很大程度上尚不清楚。全身血管生成失衡导致 HIV 未感染妇女发生子痫前期，但在开始高效抗逆转录病毒治疗（HAART）后，血管生成标志物的变化尚未得到研究。
方法
Mma Bana 研究将 560 名 CD4 计数≥200 个细胞/立方毫米的 HIV 感染、未接受 HAART 的孕妇随机分为洛匹那韦/利托那韦/齐多夫定/拉米夫定或阿巴卡韦/齐多夫定/拉米夫定组，这些孕妇的妊娠时间在 26 至 34 周之间。另外 170 名 CD4 计数每立方毫米少于 200 个细胞的参与者在 18 至 34 周妊娠期间开始接受奈韦拉平/齐多夫定/拉米夫定治疗。采用逻辑回归比较 11 名发生子痫前期的妇女的特征与其余 722 名使用 Mma Bana 分娩的参与者。从 60 名未发生子痫前期的妇女在开始 HAART 时和 1 个月后以及从所有 11 名子痫前期妇女在开始 HAART 时抽取血浆样本，测定胎盘生长因子（PlGF）和可溶性 FMS 样酪氨酸激酶-1（sFlt-1）。
结果
病毒载量大于 100000 拷贝/毫升与子痫前期相关（比值比：5.8，95%置信区间：1.8 至 19.4，P=0.004）。与未发生子痫前期的妇女相比，发生子痫前期的妇女的中位预 HAART PlGF 水平较低，sFlt-1 水平较高（130 与 992 pg/ml，P=0.001；17.5 与 9.4 pg/ml，P=0.03）。多变量分析中，PlGF 和病毒载量与子痫前期仍显著相关。在非子痫前期妇女中，在开始 HAART 治疗 1 个月后，未观察到血管生成因子的显著变化。
结论
在妊娠期间开始 HAART 的妇女中，病毒载量大于 100000 拷贝/毫升和 PlGF 预测子痫前期。在非子痫前期妇女中，在开始 HAART 治疗 1 个月后，PlGF 或 sFlt-1 的水平并未因治疗而显著改变。
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