Mentoring in Global Patient-Oriented HIV Research in the Era of COVID-19 and Universal ART

COVID-19 和通用 ART 时代全球以患者为导向的艾滋病毒研究的指导

• 批准号: 10669765
• 负责人: SHAHIN LOCKMAN
• 金额: $ 18.87万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669765
• 关键词: 2019-nCoV; Address; Adult; Africa; African; African ancestry; Age; Antimicrobial Resistance; Area; Behavior; Birth; Body Weight Changes; Body mass index; Botswana; COVID-19; COVID-19 pandemic; COVID-19 vaccination; COVID-19 vaccine; Child; Child Health; Clinical; Clinical Research; Communicable Diseases; Communities; Country; Data; Databases; Development; Diabetes Mellitus; Electronics; Enrollment; Environment; Epidemic; Evolution; Exposure to; Faculty; Fumarates; Funding; Future; Genomics; Glycosylated hemoglobin A; Goals; Grant; Growth; Guidelines; HIV; HIV Infections; HIV antiretroviral; HIV risk; HIV-1; HIV/AIDS; Health; Human immunodeficiency virus test; Incidence; Income; Individual; International Maternal Pediatric Adolescent AIDS Clinical Trials; Laboratory Research; Lead; Long COVID; Malaria; Maternal and Child Health; Mentors; Mentorship; Metabolic syndrome; Mutation; Outcome; Pattern; Persons; Population; Positioning Attribute; Postpartum Women; Pregnancy; Pregnancy Outcome; Pregnant Women; Prevalence; Prevention trial; Productivity; Protocols documentation; Randomized; Recommendation; Recurrence; Regimen; Research; Research Personnel; Research Project Grants; Resource-limited setting; Resources; Risk Factors; Role; SARS coronavirus; SARS-CoV-2 infection; SARS-CoV-2 variant; Sampling; Secure; Southern Africa; Students; Tenofovir; Testing; Time; Toxic effect; Training; Treatment Protocols; Tuberculosis; Vaccinated; Variant; Viral; Weight Gain; Woman; adverse pregnancy outcome; antenatal; antiretroviral therapy; behavioral outcome; cardiometabolic risk; cardiometabolism; career; co-infection; cohort; coronavirus disease; design; emerging pathogen; excessive weight gain; experience; follow-up; infection rate; maternal weight; metabolic rate; neurodevelopment; neuropsychiatric symptom; new pandemic; next generation; patient oriented; patient oriented research; perinatal HIV; postpartum weight; pregnant; prenatal exposure; previous epidemic; randomized trial; severe COVID-19; skills; treatment arm; treatment program

Project Summary / Abstract The primary purpose of this K24 renewal proposal is to support mentorship by Dr. Lockman of early career investigators from the US and Africa in conducting global patient-oriented research. This next generation of investigators will need to tackle ongoing global infectious disease epidemics (such HIV, COVID-19, tuberculosis, malaria, and antimicrobial resistance) and to respond rapidly to future emerging pandemics and pathogens. Effective mentorship of early career investigators to conduct clinical research in resource- constrained settings requires substantial time and effort by experienced mentors, and the need for such mentors exceeds their availability. The initial K24 project period permitted Dr. Lockman to successfully mentor more than 20 early career investigators (half of them from Africa) to lead clinical research projects, many of whom were able to quickly respond to the severe COVID-19 epidemic in Botswana because of prior training. This K24 grant also allowed Dr. Lockman to gain additional skills in designing and conducting patient-oriented research in resource-constrained settings with a focus on HIV (particularly in pregnancy) and COVID-19. Currently, nearly one in five adults in many sub-Saharan African countries is living with HIV; the impact of HIV co-infection on COVID-19 clinical outcomes and on SARS-CoV-2 viral evolution in settings with both very high HIV prevalence and high COVID incidence are unknown. In addition, the impact of widely used HIV antiretroviral treatment (ART) regimens during pregnancy on birth outcomes and on long-term maternal and child health and development are not well understood. The research aims of this project, which Dr. Lockman will mentor early career investigators from Africa and the US to lead, include studies of the role of HIV co- infection in several aspects of SARS-CoV-2 infection in Botswana -- specifically, the impact of HIV infection on long COVID and on the emergence of SARS-CoV-2 mutations/variants, by SARS-CoV-2 vaccination status. Additional mentored aims will evaluate the impact of different ART regimens during pregnancy on cardiometabolic factors in women (specifically, pregnancy and postpartum weight gain, and markers of diabetes and metabolic syndrome in pregnancy), and the association between these cardiometabolic factors and pregnancy outcomes and child health/growth. Dr. Lockman’s mentees will use existing data and samples for these aims, including from studies that she leads (multi-country IMPAACT 2010/VESTED randomized trial of 3 ART regimens in pregnancy and a new R01-funded study of child developmental/behavioral outcomes after in utero exposure to different maternal ART regimens in Botswana) and from stored clinical SARS-CoV-2 samples and related electronic routine health databases in Botswana. Dr. Lockman will also help her mentees access a wealth of other existing data, resources, and co-mentors. The overarching goal of this K24 renewal proposal is to help expand sustained capacity to conduct high-impact patient-oriented research in Africa by supporting the mentorship and training of early career investigators.

项目总结/摘要 此K24更新提案的主要目的是支持Lockman博士对早期职业生涯的指导 来自美国和非洲的研究人员进行全球以患者为导向的研究。下一代的 研究人员将需要应对持续的全球传染病流行（如艾滋病毒，COVID-19， 结核病、疟疾和抗菌素耐药性），并迅速应对未来新出现的流行病， 病原体对早期职业研究者进行有效的指导，以便在资源方面进行临床研究- 受约束的设置需要经验丰富的导师投入大量的时间和精力， 导师超出了他们的可用性。最初的K24项目期间允许博士洛克曼成功地指导 20多名早期职业研究人员（其中一半来自非洲）领导临床研究项目，其中许多人 他们能够迅速应对博茨瓦纳严重的COVID-19疫情，因为他们事先接受了培训。 这项K24资助还使洛克曼博士获得了设计和进行以患者为导向的 在资源有限的环境中开展研究，重点关注艾滋病毒（特别是怀孕期间）和COVID-19。 目前，撒哈拉以南非洲许多国家近五分之一的成年人感染艾滋病毒;艾滋病毒的影响 共同感染对COVID-19临床结局和SARS-CoV-2病毒演变的影响， 艾滋病毒流行率和COVID高发病率尚不清楚。此外，广泛使用的艾滋病毒 妊娠期抗逆转录病毒治疗（ART）方案对分娩结果和长期孕产妇和 儿童健康和发展没有得到很好的理解。这个项目的研究目标，洛克曼博士 将指导来自非洲和美国的早期职业调查人员领导，包括艾滋病毒共同作用的研究， 感染在博茨瓦纳SARS-CoV-2感染的几个方面-特别是艾滋病毒感染对 长期COVID和出现SARS-CoV-2突变/变异，按SARS-CoV-2疫苗接种状况。 额外的指导目标将评估怀孕期间不同的ART方案对 女性的心脏代谢因素（特别是妊娠和产后体重增加，以及 妊娠期糖尿病和代谢综合征），以及这些心脏代谢因素之间的关联 妊娠结局和儿童健康/生长。洛克曼博士的学员将使用现有的数据和样本 为了实现这些目标，包括她领导的研究（多国IMPAACT 2010/VESTED随机试验 妊娠期3种ART方案和一项新的R 01资助的儿童发育/行为结果研究 在博茨瓦纳子宫内暴露于不同的母体ART方案后）和储存的临床SARS-CoV-2 博茨瓦纳的样本和相关电子常规健康数据库。洛克曼博士还将帮助她的学员 访问大量其他现有数据、资源和共同导师。此次K24更新的首要目标是 该提案旨在通过以下方式帮助扩大在非洲开展高影响力的面向患者的研究的持续能力 支持对早期职业调查人员的指导和培训。

项目成果

HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.

• DOI: 10.3390/v13040594
• 发表时间: 2021-03-31
• 期刊: Viruses
• 作者: Seatla KK;Maruapula D;Choga WT;Ntsipe T;Mathiba N;Mogwele M;Kapanda M;Nkomo B;Ramaabya D;Makhema J;Mmalane M;Mine M;Kasvosve I;Lockman S;Moyo S;Gaseitsiwe S
• 通讯作者: Gaseitsiwe S

Human Immunodeficiency Virus Exposure but Not Early Cytomegalovirus Infection Is Associated With Increased Hospitalization and Decreased Memory T-Cell Responses to Tetanus Vaccine.

人类免疫缺陷病毒暴露与住院率增加和破伤风疫苗记忆 T 细胞反应降低相关，但与早期巨细胞病毒感染无关。

• DOI: 10.1093/infdis/jiz590
• 发表时间: 2020
• 期刊: The Journal of infectious diseases
• 作者: Smith,Christiana;Moraka,NatashaO;Ibrahim,Maryanne;Moyo,Sikhulile;Mayondi,Gloria;Kammerer,Betsy;Leidner,Jean;Gaseitsiwe,Simani;Li,Shaobing;Shapiro,Roger;Lockman,Shahin;Weinberg,Adriana
• 通讯作者: Weinberg,Adriana

Limited HIV-1 Subtype C nef 3'PPT Variation in Combination Antiretroviral Therapy Naïve and Experienced People Living with HIV in Botswana.

• DOI: 10.3390/pathogens10081027
• 发表时间: 2021-08-13
• 期刊: Pathogens (Basel, Switzerland)
• 作者: Seatla KK;Maruapula D;Choga WT;Morerinyane O;Lockman S;Novitsky V;Kasvosve I;Moyo S;Gaseitsiwe S
• 通讯作者: Gaseitsiwe S

Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa.

• DOI: 10.1097/qad.0000000000002741
• 发表时间: 2021-02-02
• 期刊: AIDS (London, England)
• 作者: Chandiwana NC;Chersich M;Venter WDF;Akpomiemie G;Hill A;Simmons B;Lockman S;Serenata CM;Fairlie L;Moorhouse MA
• 通讯作者: Moorhouse MA

Optimal breastfeeding durations for HIV-exposed infants: the impact of maternal ART use, infant mortality and replacement feeding risk.

• DOI: 10.1002/jia2.25107
• 发表时间: 2018-04
• 期刊: Journal of the International AIDS Society
• 影响因子: 6
• 作者: Mallampati D;MacLean RL;Shapiro R;Dabis F;Engelsmann B;Freedberg KA;Leroy V;Lockman S;Walensky R;Rollins N;Ciaranello A
• 通讯作者: Ciaranello A