Huo Yanling, Kim Jinhee, Kacanek Deborah, Samer Sadia, Livingston Elizabeth G, Machado Elizabeth Stankiewicz, Martinelli Elena
Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Department of Medicine Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
J Immunol Res. 2025 May 21;2025:4771787. doi: 10.1155/jimr/4771787. eCollection 2025.
Antiretroviral therapy (ART) during pregnancy is essential to prevent vertical HIV transmission and preserve the health of the mother and child. However, ART in pregnancy has been associated with adverse birth outcomes linked to poor placental development. Immune dysregulation of placental development is an important factor in the development of preeclampsia (PE), a common hypertension disorder of pregnancy. Some studies found an association between ART use at conception or during the first trimester and PE. However, little is known regarding the impact of timing of ART initiation on the immune environment in pregnancy. To investigate the immune environment in pregnant persons with HIV (PPWH) on ART at conception ( = 40) compared to PPWH that started ART in the second trimester ( = 40) we analyzed specimens from the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Perinatal Core Protocol, P1025, concluded in 2013. No difference was found in soluble factors in circulation including PlGF and sFLt-1, associated with PE. However, upon analysis of PBMC by high dimension flow cytometry, we detected a lower frequency of circulating CD49a NK cells, associated with uterine tissue and pregnancy, in PPWH on ART at conception compared with PPWH who started ART in the second trimester. Moreover, PBMC from PPWH on ART at conception expressed higher levels of SERPINB2 in transcriptomics analyses. Our findings shed new insights into the potential impact of ART at conception and suggest the persistence of a dysregulated inflammatory environment compared to PPWH starting ART after the conclusion of placental development.
孕期抗逆转录病毒疗法（ART）对于预防HIV垂直传播以及维护母婴健康至关重要。然而，孕期ART与胎盘发育不良相关的不良出生结局有关。胎盘发育的免疫失调是子痫前期（PE）发生发展的一个重要因素，子痫前期是一种常见的妊娠高血压疾病。一些研究发现受孕时或孕早期使用ART与子痫前期之间存在关联。然而，关于开始ART的时机对孕期免疫环境的影响知之甚少。为了研究受孕时开始接受ART治疗的HIV感染孕妇（PPWH，n = 40）与孕中期开始接受ART治疗的PPWH（n = 40）的免疫环境，我们分析了国际母婴儿科青少年艾滋病临床试验（IMPAACT）围产期核心方案P1025（于2013年结束）的标本。在与子痫前期相关的循环可溶性因子（包括胎盘生长因子（PlGF）和可溶性血管内皮生长因子受体1（sFLt-1））方面未发现差异。然而，通过高维流式细胞术分析外周血单个核细胞（PBMC）时，我们发现受孕时开始接受ART治疗的PPWH中，与子宫组织和妊娠相关的循环CD49a自然杀伤细胞频率低于孕中期开始接受ART治疗的PPWH。此外，在转录组学分析中，受孕时开始接受ART治疗的PPWH的PBMC表达更高水平的丝氨酸蛋白酶抑制剂B2（SERPINB2）。我们的研究结果为受孕时ART的潜在影响提供了新的见解，并表明与胎盘发育完成后开始接受ART治疗的PPWH相比，受孕时接受ART治疗的PPWH持续存在炎症环境失调的情况。
