Protease inhibitors and preterm delivery: another piece in the puzzle
Protease inhibitors and preterm delivery: another piece in the puzzle
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DOI：
10.1097/qad.0000000000001694
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发表时间：
2018-01-14
期刊：
影响因子：
3.8
通讯作者：
Thorne, Claire
中科院分区：
文献类型：
--
作者：
Favarato, Graziella;Townsend, Claire L.;Thorne, Claire
背景：关于接受抗逆转录病毒治疗 (ART) 的 HIV 感染妇女的早产 (PTD) 风险仍然存在疑问，包括利托那韦 (RTV) 增强的蛋白酶抑制剂的作用、ART 启动时间和免疫状态。方法：我们检查了英国/爱尔兰妊娠期和儿童期 HIV 国家研究的数据，该研究涉及 2007-2015 年感染 HIV 的妇女分娩单胎活婴，包括接受过治疗的孕妇基于 RTV 增强的蛋白酶抑制剂 (n=4184) 或基于非核苷逆转录酶抑制剂的治疗方案 (n=1889)。我们进行了逻辑回归分析，调整了与 PTD 相关的风险因素，并在受孕和 CD4(+) 细胞计数时按 ART 进行分层，以最大程度地减少治疗适应症的偏差，并评估 PTD 风险是否因 ART 类别和特定药物组合而异。结果：在接受 ART 受孕的女性中，洛匹那韦/RTV 与 CD4(+) 细胞计数 350 个细胞/升或更少的女性的 PTD 风险增加相关[比值比 1.99 (1.02, 3.85)] 且 CD4(+) 细胞计数超过 350 个细胞/升 [比值比 1.61 (1.07, 2.43)] 与同一 CD4(+) 亚组中接受非核苷逆转录酶抑制剂（主要是依非韦伦和奈韦拉平）治疗方案的女性相比。其他基于蛋白酶抑制剂的治疗方案（主要是阿扎那韦和达芦那韦）与 PTD 风险之间的关联很复杂。总体而言，接受 ART 受孕、CD4(+) 细胞计数较低且年龄较大的女性的 PTD 风险较高。没有观察到 PTD 与替诺福韦或任何特定药物组合之间的关联趋势。结论：我们的数据支持 RTV 增强/基于洛匹那韦的 ART 孕前启动与随后妊娠中的 PTD 之间存在联系，对治疗指南具有影响。随着使用新药怀孕的人数不断增加，需要持续监测 PTD 风险。
Background:Questions remain regarding preterm delivery (PTD) risk in HIV-infected women on antiretroviral therapy (ART), including the role of ritonavir (RTV)-boosted protease inhibitors, timing of ART initiation and immune status.Methods:We examined data from the UK/Ireland National Study of HIV in Pregnancy and Childhood on women with HIV delivering a singleton live infant in 2007-2015, including those pregnancies receiving RTV-boosted protease inhibitor-based (n=4184) or nonnucleoside reverse transcriptase inhibitors-based regimens (n=1889). We conducted logistic regression analysis adjusted for risk factors associated with PTD and stratified by ART at conception and CD4(+) cell count to minimize bias by indication for treatment and to assess whether PTD risk differs by ART class and specific drug combinations.Results:Among women conceiving on ART, lopinavir/RTV was associated with increased PTD risk in those with CD4(+) cell count 350 cells/l or less [odds ratio 1.99 (1.02, 3.85)] and with CD4(+) cell count more than 350 cells/l [odds ratio 1.61 (1.07, 2.43)] vs. women on nonnucleoside reverse transcriptase inhibitors-based (mainly efavirenz and nevirapine) regimens in the same CD4(+) subgroup. Associations between other protease inhibitor-based regimens (mainly atazanavir and darunavir) and PTD risk were complex. Overall, PTD risk was higher in women who conceived on ART, had low CD4(+) cell count and were older. No trend of association of PTD with tenofovir or any specific drug combinations was observed.Conclusion:Our data support a link between the initiation of RTV-boosted/lopinavir-based ART preconception and PTD in subsequent pregnancies, with implications for treatment guidelines. Continued monitoring of PTD risk is needed as increasing numbers of pregnancies are conceived on new drugs.