Early Infant Treatment

婴儿早期治疗

• 批准号: 10002381
• 负责人: Daniel R. Kuritzkes
• 金额: $ 24.98万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002381
• 关键词: Adaptive Immune System; Address; Adult; Adverse event; Affect; Age; Anti-Retroviral Agents; Birth; Boston; Botswana; CD4 Positive T Lymphocytes; Cells; Clinic; Clinical Trials; Collaborations; Control Groups; Cytometry; DNA; Data; Detection; Development; Devices; Drug Kinetics; Early treatment; Enrollment; Ethics; Evaluation; HIV; HIV Infections; HIV-1; Hour; Human immunodeficiency virus test; Immune; Immune response; Immunologic Tests; Immunologics; Infant; Infection; Interruption; Intervention Studies; Investigation; Kinetics; Lead; Life; Mass Spectrum Analysis; Measures; Memory; Monitor; Outcome; Perinatal; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Plasma; Population; Prenatal Diagnosis; RNA; Research Infrastructure; Safety; Sampling; Shapes; Site; T-Lymphocyte Subsets; Testing; Time; Viral; Viral reservoir; Viremia; adaptive immune response; antenatal; antiretroviral therapy; base; cohort; comparison group; computer studies; experience; follow-up; immune activation; infancy; memory CD4 T lymphocyte; neonatal infection; neonate; novel; postnatal; prevent; prospective; public health relevance; rapid diagnosis; stem cells; treatment adherence; viral rebound; virology; ward

DESCRIPTION (provided by applicant): Combination antiretroviral treatment (ART) initiated shortly after HIV infection may prevent seeding of a long-lasting reservoir of latently infected cells in some infants. We propose an interventional study in Botswana to screen for HIV infection from birth and provide immediate ART to infected infants. At 24 months from ART initiation, infants without viral reservoir detection will undergo a controlled treatment interrupton with close evaluation for viral rebound. We will enroll 50 HIV+ infants into two parallel early treatment cohorts: 30 infants who test HIV+ within 72 hours of birth and initiate ART at < 7 days of life, and 20 infants who test HIV- within 72 hours of birth but HIV+ within 42 days of life and initiate ART by 56 days of life. Primary study aims will evaluate safety and efficacy of early ART; virologic and immunologic outcomes with early ART; and the possibility of functional cure (or the dynamics of viral rebound) after ART interruption. In Botswana, an established research infrastructure allows rapid diagnosis of HIV infection and high rates of treatment adherence and follow-up. In Boston, specialized virologic and immunologic testing is available to study viral reservoirs and the immunologic impact of early treatment. This unique collaboration will allow for a detailed investigation of how cellular HIV reservoirs, immune responses, and mechanisms of viral long-term persistence can be manipulated through early ART initiation.

描述（由申请人提供）：在HIV感染后不久开始联合抗逆转录病毒治疗（ART）可能会阻止一些婴儿体内潜伏感染细胞的长期蓄水池的播种。我们建议在博茨瓦纳进行一项介入性研究，从出生开始筛查艾滋病毒感染，并立即向受感染的婴儿提供抗逆转录病毒治疗。在抗逆转录病毒治疗开始后24个月，未检测到病毒库的婴儿将接受有控制的治疗中断，并密切评估病毒反弹。我们将把50名艾滋病毒阳性婴儿纳入两个平行的早期治疗队列：30名婴儿在出生72小时内检测出艾滋病毒阳性，并在出生后7天内开始抗逆转录病毒治疗；20名婴儿在出生后72小时内检测出艾滋病毒，但在出生后42天内检测出艾滋病毒阳性，并在出生后56天开始抗逆转录病毒治疗。研究的主要目的是评估早期抗逆转录病毒治疗的安全性和有效性；

项目成果

HIV diagnostic algorithm requires confirmatory testing for initial indeterminate or positive screens in the first week of life.

• DOI: 10.1097/qad.0000000000002532
• 发表时间: 2020-06-01
• 期刊: AIDS (London, England)
• 作者: Ajibola G;Moyo S;Mohammed T;Moseki S;Jack D;Sakoi M;Batlang O;Maswabi K;Bennett K;Hughes MD;Lockman S;Makhema JM;Lichterfeld M;Kuritzkes DR;Shapiro RL
• 通讯作者: Shapiro RL

A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation.

• DOI: 10.7326/l21-0297
• 发表时间: 2022-01
• 期刊: ANNALS OF INTERNAL MEDICINE
• 影响因子: 39.2
• 作者: Turk, Gabriela;Seiger, Kyra;Lian, Xiaodong;Sun, Weiwei;Parsons, Elizabeth M.;Gao, Ce;Rassadkina, Yelizaveta;Polo, Maria Laura;Czernikier, Alejandro;Ghiglione, Yanina;Vellicce, Alejandra;Varriale, Joseph;Lai, Jun;Yuki, Yuko;Martin, Maureen;Rhodes, Ajantha;Lewin, Sharon R.;Walker, Bruce D.;Carrington, Mary;Siliciano, Robert;Siliciano, Janet;Lichterfeld, Mathias;Laufer, Natalia;Yu, Xu G.
• 通讯作者: Yu, Xu G.

Recent progress in understanding HIV reservoirs.

• DOI: 10.1097/coh.0000000000000441
• 发表时间: 2018-03
• 期刊: Current opinion in HIV and AIDS
• 影响因子: 4.1
• 作者: Kuo HH;Lichterfeld M
• 通讯作者: Lichterfeld M

Early antiretroviral therapy in neonates with HIV-1 infection restricts viral reservoir size and induces a distinct innate immune profile.

• DOI: 10.1126/scitranslmed.aax7350
• 发表时间: 2019-11-27
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Garcia-Broncano P;Maddali S;Einkauf KB;Jiang C;Gao C;Chevalier J;Chowdhury FZ;Maswabi K;Ajibola G;Moyo S;Mohammed T;Ncube T;Makhema J;Jean-Philippe P;Yu XG;Powis KM;Lockman S;Kuritzkes DR;Shapiro R;Lichterfeld M
• 通讯作者: Lichterfeld M

Immune correlates of HIV-1 reservoir cell decline in early-treated infants.

• DOI: 10.1016/j.celrep.2022.111126
• 发表时间: 2022-07-19
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Hartana, Ciputra Adijaya;Garcia-Broncano, Pilar;Rassadkina, Yelizaveta;Lian, Xiaodong;Jiang, Chenyang;Einkauf, Kevin B.;Maswabi, Kenneth;Ajibola, Gbolahan;Moyo, Sikhulile;Mohammed, Terence;Maphorisa, Comfort;Makhema, Joseph;Yuki, Yuko;Martin, Maureen;Bennett, Kara;Jean-Philippe, Patrick;Viard, Mathias;Hughes, Michael D.;Powis, Kathleen M.;Carrington, Mary;Lockman, Shahin;Gao, Ce;Yu, Xu G.;Kuritzkes, Daniel R.;Shapiro, Roger;Lichterfeld, Mathias
• 通讯作者: Lichterfeld, Mathias