Long – term clinical, immunologic, and virologic profiles of children who received early treatment for HIV, version 1.2
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Date
2022-04-11
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Kamuzu University of Health Sciences
Abstract
IMPAACT 2028 is an observational prospective cohort study to characterize the long-term clinical,
immunologic, and virologic profiles of early treated children who may participate in future
research related to HIV remission or cure. Up to approximately 250 children who received early
treatment for perinatally-acquired HIV in IMPAACT network studies or other research studies
sponsored by the US NIH will be enrolled and followed semi-annually for up to seven years. For
Johns Hopkins Research site, these IMAACT network studies are IMPAACT 2008 study and P1115
studies. These studies enrolled about 30 HIV positive infants who were initiated on ART at about 12
weeks of age. In IMPAACT 2008, infants were randomized to either an arm where they received a
broadly Neutralizing Antibodies (bNabs) with combined ART or only bNabs.
Longitudinal tracking of these participants will simultaneously advance the understanding of
the long-term effects of early ART and/or broadly Neutralizing Antibodies (bNabs)initiation and
will address scientific questions and promote innovation in this field.
The information obtained at the end of the study will be summarized in scientific manuscripts and
will be submitted to peer review journals. Dissemination will occur at international and local
conferences such as College of Medicine Research Dissemination Conference.Background information and introduction:
In 2013, the World Health Organization (WHO) recommended antenatal HIV testing and
immediate initiation of antiretroviral therapy (ART) for all pregnant women living with HIV,
resulting in a dramatic decline in perinatal HIV transmission. Nevertheless, there were still
160,000 new pediatric HIV infections in 2018, with only 50% of these children accessing ART, thus
emphasizing the need for HIV remission and cure research in this age group.
Early and very early ART also limits latent reservoir size and reduces the persistence of long-lived
HIV- infected cells. Additionally, virologically suppressed adolescents with controlled HIV
replication from infancy due to effective ART have a lower reservoir size than adolescents in whom
HIV replication was poorly controlled until later in childhood. Achieving low HIV reservoir size
through early or very early ART provides a permissive state for HIV ART-free remission or cure.Objectives of the study
Primary
To characterize the long-term clinical, immunologic, and virologic
profiles of children who received early treatment for perinatally-acquired HIV.
Specific
-To study the effect of acquired co-infections on reservoir dynamics,
-To study the long-term effects of ART and/or bNAbs on a maturing immune system and on the
evolution of HIV specific neutralizing antibodies, cell-mediated immunity, systemic immune
activation, inflammation, and the predictive value of biomarkers associated with increased morbidity
and mortality
Secondary
-To establish a pediatric cohort who received early treatment for HIV and may be eligible for future
studies of interventions for HIV remission or cure.
-To establish a biorepository for further investigation of the long-term effects of early ART and the
developing immune system. Expected findings
-Very early compared to early ART will lead to improved immune health and lower levels of
immune activation and exhaustion.Addition of a bNAb to very early and early ART will lead to improved immune outcomes
-Very early compared to early ART will lead to more durable responses to routine childhood
vaccines
-Addition of a bNAb to very early and early ART will induce a vaccinal effect and manifest as
durable HIV-1-specific responses
-Very early compared to early ART will lead to less gut dysbiosis
-A healthy microbiome is correlated with immune health in perinatal HIV infection
-Intermittent episodes of viremia may boost autologous HIV-1 neutralization
antibody responses and HIV-1 cellular immune responses
-Very early compared to early treatment will lead to sustained lower reservoir size
including lower intact proviral reservoir size
-Addition of a bNAb to very early and early ART will lead to lower intact proviral reservoir size
-Addition of a bNAb to very early and early ART will modify the reservoir
composition
-Intermittent episodes of viremia may lead to clonal amplification or depletion
of HIV-1 reservoir cells
Dissemination of the Results
The information obtained will be summarized in scientific manuscripts and will be submitted to
peer review journals. Participants and other stakeholders will have access to the information.
The results will be used as needed to inform policy makers regarding future HIV prevention
options. This information will also be disseminated through international and local conferences
including the College of Medicine Dissemination Conference in Malawi
Description
Type of Study
Observational prospective cohort study