Bone health in perinatally HIV-infected South African children on antiretrovirals

服用抗逆转录病毒药物的围产期感染艾滋病毒的南非儿童的骨骼健康

• 批准号: 9085322
• 负责人: Stephen M Arpadi
• 金额: $ 71.69万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-16 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9085322
• 关键词: 15 year old; 2 year old; Adolescence; Adolescent; Adult; Affect; Age; Archives; Blood specimen; Bone Density; Bone Mineral Contents; Bone remodeling; Child; Childhood; Chronic; Cohort Studies; Country; Data; Developed Countries; Development; Dual-Energy X-Ray Absorptiometry; Enrollment; Environment; Exposure to; Fracture; Future; Genetic; Goals; Growth; HIV; HIV Infections; HIV antiretroviral; Hormonal; Immune; Individual; Infection; Inflammatory; Intervention; Intervention Studies; Ionizing radiation; Life; Lopinavir/Ritonavir; Measurement; Measures; Mediating; Methods; Minerals; Modality; Monitor; Nutritional; Observational Study; Osteoblasts; Osteoclasts; Outcome; Pathogenesis; Pathway interactions; Perinatal; Physical activity; Postmenopause; Protein-Energy Malnutrition; Puberty; Publishing; Randomized Controlled Trials; Regimen; Reporting; Research; Research Infrastructure; Research Priority; Resources; Risk; Risk Factors; Sexual Maturation; South Africa; South African; Specimen; Time; Tuberculosis; Up-Regulation; Viral; Virus; Vitamin D; Woman; Youth; antiretroviral therapy; base; bone; bone health; bone mass; bone metabolism; bone quality; bone turnover; co-infection; cytokine; early adolescence; efavirenz; immune activation; improved; innovation; mathematical model; men; microbial; micronutrient deficiency; modifiable risk; non-nucleoside reverse transcriptase inhibitors; nutrition; older men; osteoclastogenesis; osteoporosis with pathological fracture; prospective; quantitative ultrasound; repository; sex; skeletal; skeletal abnormality

DESCRIPTION (provided by applicant): While skeletal abnormalities, including decreased bone mineral content (BMC) and bone mineral density (BMD), are well described among HIV-infected children and adolescents in highly developed nations, no studies have been conducted in resource constrained settings (RCS), where >90% of HIV-infected youth now live. Recent studies of adult HIV+ infected individuals demonstrate that fracture rates are higher in postmenopausal and older men and possibly higher in younger HIV+ men and women as well. Multiple factors appear to be involved, including potential direct effects of virus on osteoblast and osteoclast differentiation and function, indirect effects of inflammatory cytokines on osteoclast resorption and effects of antiretroviral therapy (ART) on osteoclastogenesis and osteoblast activity. Perinatally HIV-infected individuals have the greatest cumulative life-time exposure to both the direct and indirect effects of HIV infection as well as to those associated with ART. Among 2.2 million HIV-infected children living in RCS, including over 356,000 on ART, additional factors including protein and energy malnutrition, micronutrient deficiencies, and childhood infections that are known to adversely affect bone mass accrual and are highly prevalent, may pose additional threats to bone acquisition. Risk of fracture in adulthood is strongly related to "peak bone mass" reached in late adolescence. Therefore, reduced bone accrual during late childhood and adolescence, as reported among those with HIV, may increase the risk of osteoporotic fractures later in life. In the proposed study we will 1) assess bone turnover markers, bone density and quality, and rate of bone acquisition; 2) evaluate the contribution of upregulation of pro-inflammatory cytokines, nutrition and physical activity on bone turnover and accrual; and 3) compare the effects of lopinavir/ritonavir-based versus efavirenz-based regimens on vitamin D levels, bone turnover, and bone acquisition in pre-pubertal perinatally HIV-infected children in South African who initiated ART prior to age 2 years. This 2 country collaborative 5 year project proposes to conduct a 2 year longitudinal observational study that will be an extension study for HIV+ children ages 8-10 years who participated in a randomized controlled trial of continued PI-based vs. switch to NNRTI-based ART (NEVEREST3) that is currently being conducted. Our proposed study will exploit the research infrastructure as well as the research-quality antecedent data and specimens obtained in NEVEREST. This will greatly expand both the timeframe and the variables that will be assessed with respect to bone outcomes. For comparisons, age appropriate HIV-uninfected children will also be enrolled. Our goal is to identify potentially modifiable factors for poor bon accrual and to develop a framework for future research, including intervention studies suitable for HIV-infected children in RCS.

描述(由申请人提供)：虽然骨骼异常，包括骨矿含量(BMC)和骨密度(BMD)减少，在高度发达国家感染艾滋病毒的儿童和青少年中得到了很好的描述，但尚未在资源受限的环境(RCS)中进行研究，目前90%的艾滋病毒感染青年生活在那里。最近对成年艾滋病毒感染者的研究表明，绝经后和老年男性的骨折发生率更高，年轻的艾滋病毒感染者和女性的骨折发生率也可能更高。可能涉及多种因素，包括病毒对成骨细胞和破骨细胞分化和功能的潜在直接影响，炎性细胞因子对破骨细胞吸收的间接影响，以及抗逆转录病毒疗法(ART)对破骨细胞生成和成骨细胞活性的影响。围产期感染艾滋病毒的人一生中对艾滋病毒感染的直接和间接影响以及与抗逆转录病毒治疗有关的影响的累积暴露最多。在生活在RCS的220万感染艾滋病毒的儿童中，包括接受抗逆转录病毒治疗的356,000多名儿童中，其他因素，包括蛋白质和能量营养不良、微量营养素缺乏以及已知对骨量积累产生不利影响且非常普遍的儿童感染，可能对骨获取构成额外威胁。成年时骨折的风险与青春期后期达到的“峰值骨量”密切相关。因此，艾滋病毒携带者在儿童和青春期后期骨积累减少，可能会增加日后骨质疏松性骨折的风险。在拟议的研究中，我们将1)评估骨转换标记物、骨密度和质量，以及骨获取速度；2)评估促炎细胞因子上调、营养和体力活动对骨转换和收益的贡献；3)比较基于洛匹那韦/利托那韦和基于efavirenz的治疗方案对维生素D水平、骨转换和骨获取的影响。这个两国合作的五年项目提议进行一项为期两年的纵向观察性研究，这将是一项针对8-10岁艾滋病毒+儿童的扩展研究，这些儿童参加了目前正在进行的继续基于PI的抗逆转录病毒疗法与转向基于NNRTI的抗逆转录病毒疗法(NEVEREST3)的随机对照试验。我们提议的研究将利用研究基础设施以及在Neverest获得的研究质量的先例数据和样本。这将极大地扩展时间框架和将被评估的关于骨骼结果的变量。为了进行比较，年龄合适的未感染艾滋病毒的儿童也将被纳入其中。我们的目标是找出贫穷的潜在可改变因素，并为未来的研究开发一个框架，包括适合于RCS中HIV感染儿童的干预研究。

项目成果

Bone Update: Is It Still an Issue Without Tenofovir Disoproxil Fumarate?

• DOI: 10.1007/s11904-019-00474-1
• 发表时间: 2020-03
• 期刊: Current HIV/AIDS reports
• 影响因子: 4.6
• 作者: Shiau S;Arpadi SM;Yin MT
• 通讯作者: Yin MT

Decreased bone turnover in HIV-infected children on antiretroviral therapy.

• DOI: 10.1007/s11657-018-0452-6
• 发表时间: 2018-04-05
• 期刊: Archives of osteoporosis
• 影响因子: 3
• 作者: Shiau S;Yin MT;Strehlau R;Patel F;Mbete N;Kuhn L;Coovadia A;Arpadi SM
• 通讯作者: Arpadi SM

Bone health in HIV-infected children, adolescents and young adults: a systematic review.

艾滋病毒感染儿童、青少年和年轻人的骨骼健康：系统评价。

• DOI: 10.4172/2155-6113.1000374
• 发表时间: 2014
• 期刊: Journal of AIDS & clinical research
• 作者: Arpadi,StephenM;Shiau,Stephanie;Marx-Arpadi,Charlotte;Yin,MichaelT
• 通讯作者: Yin,MichaelT