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Principal Investigator: Roger L Shapiro
Organization: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
Fiscal Year: 2024
Award: $1,195,048
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Overall Project Summary/Abstract
Antiretroviral treatment (ART) options for pregnant women and children living with HIV have fallen behind those
for adults, reflecting the substantial research gap for modern ART regimens in these groups. Safety and efficacy
studies of specific ART regimens in pregnancy, and strategies for starting modern ART in early infancy, have
become research priorities. Here we propose a series of interrelated projects that expand the scientific objectives
and data utilization of a valuable NIH-funded nationwide birth surveillance system in Botswana (the Tsepamo
Study), and connect it with the infrastructure provided by an existing program for identifying and treating infants
with HIV (the Early Infant Treatment Study, or EIT). The four proposed projects, anchored by administrative and
data cores, include:
1) Tsepamo Plus: Expanded Congenital Abnormalities Surveillance and an Emulated Clinical Trial to
Evaluate Weight Impact on Birth Outcomes for Newer ART Regimens: an expanded surveillance program
for neural tube defects and other congenital abnormalities following exposure to modern ART regimens, and an
emulated clinical trial to address critical questions related to use of ART regimens by maternal weight strata.
2) Methodology: Developing Reporting Criteria for Pregnancy Surveillance Cohorts and New Techniques
for Supporting Target Trials: the creation of surveillance reporting criteria in pregnancy cohorts and validation
of a target trial approach to ART regimen comparisons.
3) Point-of-Care HIV Testing and Early Dolutegravir Use for Infants: a new approach to targeted facility-
based point-of-care HIV testing, combined with an optimized ART management strategy that uses dolutegravir
from early infancy.
4) Pioneering Precision Medicine Approaches for Immune Control of Pediatric HIV-1 Infection: utilizing
shared data and infrastructure to efficiently obtain specimens, this project will bank HIV sequences from early-
treated infants, measure and compare viral reservoir and chromosomal positioning between ART regimens, and
study immune responses to mRNA vaccines among children with HIV to begin development of an mRNA HIV
vaccine program for children in Botswana.
This P01 brings together a group of experienced investigators who will forge a cohesive research program using
the unique data sources and outstanding physical infrastructure available from the Tsepamo and EIT research
programs in Botswana. Each project addresses key scientific issues related to ART use during pregnancy and
initiation of ART in early infancy, and together they will efficiently close research gaps for women and children
with HIV.
Terms: <0-11 years old><21+ years old><AIDS Virus><AIDS test><AIDS/HIV test><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Adult><Adult Human><Bechuanaland><Birth><Birth Defects><Botswana><Child><Child Youth><Children (0-21)><Clinical Trials><Collaborations><Congenital Abnormality><Congenital Anatomical Abnormality><Congenital Defects><Congenital Deformity><Congenital Malformation><Data><Data Sources><Development><Diagnosis><Exposure to><Funding><Gestation><HIV><HIV test><HIV vaccine><HIV-1><HIV-1 test><HIV-2 test><HIV-I><HIV/AIDS Vaccines><HIV1><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Human immunodeficiency virus test><Immune><Immune response><Immunes><Immunological response><Infant><Infection><Infrastructure><Investigators><LAV-HTLV-III><Laboratories><Lymphadenopathy-Associated Virus><Measures><Messenger RNA><Methodology><Modernization><NIH><National Institutes of Health><Neural Tube Defects><Neural Tube Developmental Defects><Outcome><Parturition><Performance><Pregnancy><Pregnant Women><Principal Investigator><RNA vaccine><RNA-based vaccine><Reporting><Research><Research Personnel><Research Priority><Research Specimen><Researchers><Series><Specimen><Surveillance Program><System><Techniques><Treatment Protocols><Treatment Regimen><Treatment Schedule><United States National Institutes of Health><Validation><Viral reservoir><Virus reservoir><Virus-HIV><Weight><Woman><Work><adulthood><antiretroviral therapy><antiretroviral treatment><chromosomal location><chromosomal position><chromosome location><cohort><data management><data sharing><developmental><efficacy study><expectant mother><expecting mother><experience><forging><high risk infant><host response><human immunodeficiency virus vaccine><immune system response><immunoresponse><infancy><infantile><kids><mRNA><mRNA vaccine><mRNA-based vaccine><maternal weight><neonate><new approaches><novel approaches><novel strategies><novel strategy><pediatric HIV><pediatric HIV disease><pediatric HIV infection><pediatric human immunodeficiency virus><pediatric human immunodeficiency virus disease><pediatric human immunodeficiency virus infection><point of care><point-of-care diagnostics><precision medicine><precision-based medicine><pregnant mothers><programs><safety study><therapy optimization><treatment guidelines><treatment optimization><treatment strategy><validations><vulnerable infant><weights><youngster>