Lucia Baquero, Sofía Stöver, Marie Armani Tourret, Ailén Perbelis, Alejandra Urioste, Ariel Amadeo Osegueda Peña, Leonel Hernán Cruces, Patricia Coll Cardenas, Jorge Lattner, Alicia Sisto, María José Rolón, Solange Arazi, Yanina Ghiglione, Maria Laura Polo, Xu G Yu, Mathias Lichterfeld, Gabriela Turk, Natalia Laufer
{"title":"围产期感染艾滋病病毒的年轻成人的免疫表型和病毒载体组成存在差异:是否需要特殊的治疗策略?","authors":"Lucia Baquero, Sofía Stöver, Marie Armani Tourret, Ailén Perbelis, Alejandra Urioste, Ariel Amadeo Osegueda Peña, Leonel Hernán Cruces, Patricia Coll Cardenas, Jorge Lattner, Alicia Sisto, María José Rolón, Solange Arazi, Yanina Ghiglione, Maria Laura Polo, Xu G Yu, Mathias Lichterfeld, Gabriela Turk, Natalia Laufer","doi":"10.1097/QAD.0000000000004075","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To characterize the immune functionality and phenotype and the proviral composition of a cohort of young adults with perinatally-acquired HIV (p-YA) from Argentina.</p><p><strong>Design: </strong>Cross-sectional study of 18 p-YA, 15 young adults with non-perinatally acquired HIV matched by age with p-YA and 14 adults with non-perinatally acquired HIV, matched by time from HIV diagnosis with p-YA, all from Argentina.</p><p><strong>Methods: </strong>Immune memory/effector phenotype, exhaustion, activation, PTK-7 and Ki-67 expression were evaluated by flow cytometry on NK and T-cells. Total, intact and defective proviral (TP, IP and DP) HIV-DNA were measured in CD4 T-cells by IPDA. Soluble markers were determined by ELISA.</p><p><strong>Results: </strong>p-YA displayed lower expression of PD-1, higher levels of CD38+ CD4 T-cells and increased levels of naïve T-cells than control groups. Also, a trend of lower levels of IP HIV-DNA normalized to CD4 T-cell counts and to the proportion of naïve T-cells was found in p-YA.</p><p><strong>Conclusion: </strong>The higher frequency of naïve CD4 T-cells in p-YA cannot be explained by elevated thymic activity nor by a higher T-cell proliferation rate. This imbalance could have been generated early in life and persisted during adulthood. Naïve CD4 T-cells may not serve as a major viral reservoir in p-YA. Also, the lower PD-1+ CD4 T-cell count suggests that p-YA did not present higher levels of exhaustion. These findings suggest that acquiring HIV perinatally may imply different challenges for proviral eradication.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Differential immunophenotype and proviral composition in young adults with perinatally acquired HIV: Are special cure strategies needed?\",\"authors\":\"Lucia Baquero, Sofía Stöver, Marie Armani Tourret, Ailén Perbelis, Alejandra Urioste, Ariel Amadeo Osegueda Peña, Leonel Hernán Cruces, Patricia Coll Cardenas, Jorge Lattner, Alicia Sisto, María José Rolón, Solange Arazi, Yanina Ghiglione, Maria Laura Polo, Xu G Yu, Mathias Lichterfeld, Gabriela Turk, Natalia Laufer\",\"doi\":\"10.1097/QAD.0000000000004075\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To characterize the immune functionality and phenotype and the proviral composition of a cohort of young adults with perinatally-acquired HIV (p-YA) from Argentina.</p><p><strong>Design: </strong>Cross-sectional study of 18 p-YA, 15 young adults with non-perinatally acquired HIV matched by age with p-YA and 14 adults with non-perinatally acquired HIV, matched by time from HIV diagnosis with p-YA, all from Argentina.</p><p><strong>Methods: </strong>Immune memory/effector phenotype, exhaustion, activation, PTK-7 and Ki-67 expression were evaluated by flow cytometry on NK and T-cells. Total, intact and defective proviral (TP, IP and DP) HIV-DNA were measured in CD4 T-cells by IPDA. Soluble markers were determined by ELISA.</p><p><strong>Results: </strong>p-YA displayed lower expression of PD-1, higher levels of CD38+ CD4 T-cells and increased levels of naïve T-cells than control groups. Also, a trend of lower levels of IP HIV-DNA normalized to CD4 T-cell counts and to the proportion of naïve T-cells was found in p-YA.</p><p><strong>Conclusion: </strong>The higher frequency of naïve CD4 T-cells in p-YA cannot be explained by elevated thymic activity nor by a higher T-cell proliferation rate. This imbalance could have been generated early in life and persisted during adulthood. Naïve CD4 T-cells may not serve as a major viral reservoir in p-YA. Also, the lower PD-1+ CD4 T-cell count suggests that p-YA did not present higher levels of exhaustion. These findings suggest that acquiring HIV perinatally may imply different challenges for proviral eradication.</p>\",\"PeriodicalId\":7502,\"journal\":{\"name\":\"AIDS\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-11-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"AIDS\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/QAD.0000000000004075\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"AIDS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/QAD.0000000000004075","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的描述阿根廷围产期感染艾滋病病毒(p-YA)的年轻成人群体的免疫功能、表型和病毒载体组成:横断面研究:18 名 p-YA、15 名年龄与 p-YA 相匹配的非围产期感染 HIV 的年轻成人和 14 名年龄与 p-YA 相匹配的非围产期感染 HIV 的成人,所有研究对象均来自阿根廷:方法: 通过流式细胞术对 NK 细胞和 T 细胞的免疫记忆/效应表型、衰竭、活化、PTK-7 和 Ki-67 表达进行评估。通过 IPDA 测定 CD4 T 细胞中总的、完整的和有缺陷的前病毒(TP、IP 和 DP)HIV-DNA。结果:与对照组相比,p-YA 组的 PD-1 表达较低,CD38+ CD4 T 细胞水平较高,幼稚 T 细胞水平较高。此外,还发现 p-YA 组的 IP HIV-DNA 水平与 CD4 T 细胞计数和幼稚 T 细胞比例呈正常化趋势:结论:p-YA中幼稚CD4 T细胞的频率较高,这既不能用胸腺活性升高来解释,也不能用T细胞增殖率较高来解释。这种不平衡可能在生命早期就已产生,并在成年期持续存在。在 p-YA 中,幼稚的 CD4 T 细胞可能不是主要的病毒库。此外,较低的 PD-1+ CD4 T 细胞数量也表明,p-YA 的衰竭程度并不高。这些研究结果表明,围产期感染艾滋病毒可能意味着根除病毒所面临的不同挑战。
Differential immunophenotype and proviral composition in young adults with perinatally acquired HIV: Are special cure strategies needed?
Objective: To characterize the immune functionality and phenotype and the proviral composition of a cohort of young adults with perinatally-acquired HIV (p-YA) from Argentina.
Design: Cross-sectional study of 18 p-YA, 15 young adults with non-perinatally acquired HIV matched by age with p-YA and 14 adults with non-perinatally acquired HIV, matched by time from HIV diagnosis with p-YA, all from Argentina.
Methods: Immune memory/effector phenotype, exhaustion, activation, PTK-7 and Ki-67 expression were evaluated by flow cytometry on NK and T-cells. Total, intact and defective proviral (TP, IP and DP) HIV-DNA were measured in CD4 T-cells by IPDA. Soluble markers were determined by ELISA.
Results: p-YA displayed lower expression of PD-1, higher levels of CD38+ CD4 T-cells and increased levels of naïve T-cells than control groups. Also, a trend of lower levels of IP HIV-DNA normalized to CD4 T-cell counts and to the proportion of naïve T-cells was found in p-YA.
Conclusion: The higher frequency of naïve CD4 T-cells in p-YA cannot be explained by elevated thymic activity nor by a higher T-cell proliferation rate. This imbalance could have been generated early in life and persisted during adulthood. Naïve CD4 T-cells may not serve as a major viral reservoir in p-YA. Also, the lower PD-1+ CD4 T-cell count suggests that p-YA did not present higher levels of exhaustion. These findings suggest that acquiring HIV perinatally may imply different challenges for proviral eradication.
期刊介绍:
Publishing the very latest ground breaking research on HIV and AIDS. Read by all the top clinicians and researchers, AIDS has the highest impact of all AIDS-related journals. With 18 issues per year, AIDS guarantees the authoritative presentation of significant advances. The Editors, themselves noted international experts who know the demands of your work, are committed to making AIDS the most distinguished and innovative journal in the field. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.