Document text
Principal Investigator: Daniel R. Kuritzkes
Organization: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
Fiscal Year: 2024
Award: $301,913
Funding agency: National Institute of Allergy and Infectious Diseases
The Dual bNAb Treatment in Children Study (“Tatelo”) is an ongoing phase I/II, multi-site clinical trial of dual
treatment with two broadly neutralizing monoclonal antibodies (bNAbs), VRC01LS and 10-1074, offered to
HIV-1 infected virally suppressed children. The study is evaluating the efficacy of dual bNAbs for maintaining
viral suppression in the absence of ART among virally suppressed HIV-infected children who started standard
ART within 96 hours of birth (or soon after intrapartum infection).
All children in the Tatelo Study were recruited from the Early Infant Treatment (EIT) study (U01AI114235),
and have been followed from birth with frequent assessments of their clinical, virologic and immunologic
characteristics. Children who received at least 96 weeks of ART and met virologic entry criteria were offered
enrollment into the Tatelo Study. The intervention consisted of two PK and safety phases (single and then
dual bNAbs), followed by the main study intervention (dual bNAbs plus ART for at least 8 weeks, then dual
bNAbs alone for up to 24 weeks), and then a follow-up period when children were returned to ART alone.
The study is designed to evaluate three possible benefits of dual bNAb therapy in HIV-1-infected children:
1) to determine the duration of virologic control that can be maintained with dual bNAb treatment following
early ART, providing proof-of-concept that bNAbs may serve as a possible alternative to standard ART in
children with low viral reservoirs; 2) to investigate whether bNAb therapy is associated with changes in the
size and/or the cellular or clonal composition of residual viral reservoirs, which will be highly informative for
developing strategies to limit viral persistence and to destabilize viral reservoir homeostasis in pediatric
patients; and 3) to evaluate whether treatment with bNAbs is associated with qualitative or quantitative
changes in innate or adaptive antiviral immune responses, and if it facilitates the development of an
antiviral immune profile that can enable spontaneous post-treatment viral control.
Terms: <0-11 years old><21+ years old><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Active Follow-up><Adult><Adult Human><After Care><After-Treatment><Aftercare><Anti-Retroviral Agents><Antibody Therapy><Archives><Assay><Autologous><Autoregulation><Bechuanaland><Binding><Bioassay><Biological Assay><Birth><Blood Plasma><Blood Sample><Blood specimen><Botswana><CD4 Cells><CD4 Lymphocyte Count><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ Cell Counts><CD4+ Counts><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><COVID-19><CV-19><Cell Body><Cells><Characteristics><Child><Child Youth><Children (0-21)><Chromosomes><Clinical><Clinical Data><Clinical Evaluation><Clinical Markers><Clinical Research><Clinical Study><Clinical Testing><Clinical Trials><Complex><Coronavirus Infectious Disease 2019><Coupled><DNA><Data><Deoxyribonucleic Acid><Dose><Drug Kinetics><Drugs><Enrollment><Evaluation><Evolution><Failure><Frequencies><Gene Expression><Generalized Growth><Growth><HIV><HIV Genome><HIV-1><HIV-1 genome><HIV-I><HIV1><HIV1 genome><Homeostasis><Hour><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Immune><Immune Cell Activation><Immune Markers><Immune mediated therapy><Immune response><Immune system><Immunes><Immunochemical Immunologic><Immunologic><Immunologic Markers><Immunological><Immunological response><Immunologically><Immunologically Directed Therapy><Immunologics><Immunotherapy><Infant><Infection><Innate Immune Response><Interruption><Intervention><Intervention Strategies><Intervention Studies><Kinetics><LAV-HTLV-III><Length><Life><Long-term Follow-up><Longterm Follow-up><Lymphadenopathy-Associated Virus><Maintenance><Measurement><Medication><Molecular Interaction><Monitor><Monoclonal Antibody Therapy><Multi-Institutional Clinical Trial><Multi-center clinical trial><Multi-site clinical trial><Multicenter clinical trial><Multisite clinical trial><Non-Polyadenylated RNA><Outcome><PBMC><Participant><Parturition><Peripheral Blood Mononuclear Cell><Pharmaceutical Preparations><Pharmacokinetics><Phase><Phenotype><Physiological Homeostasis><Plasma><Plasma Serum><Population><RNA><RNA Gene Products><RNA Seq><RNA sequencing><RNAseq><Research Infrastructure><Residual><Residual state><Reticuloendothelial System, Serum, Plasma><Ribonucleic Acid><Safety><Serious Adverse Event><Severe Adverse Event><Severities><Site><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocyte Count><T4 Lymphocytes><Testing><Time><Tissue Growth><Variant><Variation><Viral><Viral reservoir><Virus><Virus reservoir><Virus-HIV><Withdrawal><active followup><adaptive immune response><adulthood><anti-retroviral><anti-viral development><anti-viral drug development><anti-viral efficacy><anti-viral therapeutic development><anti-viral therapy development><antibody based therapies><antibody treatment><antibody-based therapeutics><antibody-based treatment><antiviral development><antiviral drug development><antiviral therapeutic development><antiviral therapy development><child patients><clinical test><cohort><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><design><designing><determine efficacy><developing anti-viral agent><developing anti-viral drug><developing anti-viral therapeutic><developing anti-viral therapy><developing antiviral agent><developing antiviral drug><developing antiviral therapeutic><developing antiviral therapy><drug/agent><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><enroll><evaluate efficacy><examine efficacy><exhaustion><experience><follow up><follow-up><followed up><followup><host response><immune activation><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based biomarkers><immune-based therapies><immune-based treatments><immuno therapy><immunological biomarkers><immunological markers><immunoresponse><intervention research><interventional research><interventional strategy><interventional study><interventions research><intrapartum><kids><long-term followup><longterm followup><mAB-based therapy><mAb therapy><mAb-based therapeutics><neutralizing antibody><neutralizing mAb><neutralizing monoclonal antibodies><novel><ontogeny><open label><open label study><pediatric patients><post treatment><primary end point><primary endpoint><recruit><research clinical testing><secondary end point><secondary endpoint><serious adverse experience><serious adverse reaction><small molecule><success><thymus derived lymphocyte><timeline><transcriptome sequencing><transcriptomic sequencing><treatment effect><viral rebound><virus rebound><youngster>