Sharing Data and Transferring Samples Within Pediatric Clinical Studies: How to Overcome Challenges and Make Them a Science Opportunity.

EPIICAL (Early treated Perinatally HIV-Infected individuals: Improving Children's Actual Life) is a consortium of European and non-European research-driven organizations inter-connected with the aim of establishing a clinical and experimental platform for the early identification of novel therapeutic strategies for the pediatric Human Immunodeficiency Virus (HIV). Within the EPIICAL project, several pediatric clinical studies were conducted, requiring the collection and transfer of biological samples and associated data across boundaries within and outside Europe. To ensure compliance with the applicable rules on pediatric data and sample transfer and to support the efforts of academic partners, which may not always have the necessary expertise and resources in place for designing, managing and conducting multi-national studies, the consortium established a dedicated expert Working Group.

Early inflammation as a footprint of increased mortality risk in infants living with HIV from three African countries.

In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation.

Analytical treatment interruption in children living with HIV: position statement from the EPIICAL consortium.

Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted.

Accelerated CD8 T cell maturation in infants with perinatal HIV infection.

In perinatal HIV infection, early antiretroviral therapy (ART) initiation is recommended but questions remain regarding infant immune responses to HIV and its impact on immune development. Using single cell transcriptional and phenotypic analysis we evaluated the T cell compartment at pre-ART initiation of infants with perinatally acquired HIV from Maputo, Mozambique (Towards AIDS Remission Approaches cohort). CD8 T cell maturation subsets exhibited altered distribution in HIV exposed infected (HEI) infants relative to HIV exposed uninfected infants with reduced naive, increased effectors, higher frequencies of activated T cells, and lower frequencies of cells with markers of self-renewal.

Longitudinal analysis of innate immune system in infants with perinatal HIV infection until 18 months of age.

With the advent of antiretroviral therapy (ART), perinatal HIV infection is declining globally but prevalence in Sub-Saharan Africa is still greater than other nations. The relationship of HIV replication in early infancy and the developing immune system is not well understood. In this study, we investigated cellular components of the innate immune system including Natural Killer (NK) cells, monocytes, and Dendritic Cells (DC) in a cohort of HIV exposed infected (HEI) and age-matched HIV exposed uninfected (HEU) infants from Mozambique.

B-cell immunity and vaccine induced antibody protection reveal the inefficacy of current vaccination schedule in infants with perinatal HIV-infection in Mozambique, Africa.

Background: Despite antiretroviral treatment (ART), immune dysfunction persists in children with perinatal HIV infection (HEI). Here we investigated the impact of HIV status on maternal antibody (Ab) passage, long-term vaccine induced immunity and B-cell maturation.

Methods: 46 HIV Exposed Uninfected (HEU), 43 HEI, and 15 HIV unexposed uninfected (HUU) infants were vaccinated with 3 doses of DTaP-HepB-Hib-PCV10-OP at 2, 3, and 4 months at Matola Provincial Hospital, Maputo, Mozambique.

Novel Approaches to Postnatal Prophylaxis to Eliminate Vertical Transmission of HIV.

Despite progress in providing antiretroviral therapy to pregnant women living with HIV, a substantial number of vertical transmissions continue to occur. Novel approaches leveraging modern potent, safe, and well-tolerated antiretroviral drugs are urgently needed.

HIV-1 reservoir evolution in infants infected with clade C from Mozambique.

Background: The persistence of HIV-1-infected cells during antiretroviral therapy is well documented but may be modulated by early initiation of antiretroviral therapy in infants.

Methods: Here, we longitudinally analyzed the proviral landscape in nine infants with vertical HIV-1 infection from Mozambique over a median period of 24 months, using single-genome, near full-length, next-generation proviral sequencing.

Results: We observed a rapid decline in the frequency of intact proviruses, leading to a disproportional under-representation of intact HIV-1 sequences within the total number of HIV-1 DNA sequences after 12-24 months of therapy.

Viral Response among Early Treated HIV Perinatally Infected Infants: Description of a Cohort in Southern Mozambique.

Early initiation of antiretroviral therapy and adherence to achieve viral load suppression (VLS) are crucial for reducing morbidity and mortality of perinatally HIV-infected infants. In this descriptive cohort study of 39 HIV perinatally infected infants, who started treatment at one month of life in Mozambique, we aimed to describe the viral response over 2 years of follow up. VLS ≤ 400 copies/mL, sustained VLS and viral rebound were described using a Kaplan-Meier estimator.

Machine learning outperformed logistic regression classification even with limit sample size: A model to predict pediatric HIV mortality and clinical progression to AIDS.

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes.

Caregivers' psychosocial assessment for identifying HIV-infected infants at risk of poor treatment adherence: an exploratory study in southern Mozambique.

Psychosocial support (PSS) to caregivers of HIV-infected infants on antiretroviral treatment (ART) is crucial to ensure ART adherence and sustained long-term viral suppression in children. A specific approach including tools to monitor and understand adherence behavior and risk factors that prevent optimal treatment compliance are urgently needed. This qualitative exploratory study, conducted in southern Mozambique, monitored the infants' viral response trajectories during 18 months follow-up, as a measure of adherence, reviewed the caregiver's PSS session notes and the answers to a study questionnaire, to analyze whether the standard PSS checklist applied to infants' caregivers can identify barriers influencing their adherence.

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence.

Background: The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery.

Correlates of loss to follow-up and missed diagnosis among HIV-exposed infants throughout the breastfeeding period in southern Mozambique.

Introduction: Complete follow-up of human immunodeficiency virus (HIV)-exposed infants (HEI) is crucial for a successful prevention of mother-to-child HIV transmission. This study analyzed the HEI follow-up and factors associated with loss to follow-up (LTFU) in southern Mozambique.

Methods: This retrospective cohort study used the data of HEI enrolled between June 2017 and June 2018, followed-up for 18 months.

High proportion of unknown HIV exposure status among children aged less than 2 years: An analytical study using the 2015 National AIDS Indicator Survey in Mozambique.

Background: Determination of the human immunodeficiency virus (HIV) exposure status in infants and young children is required to guarantee timely diagnosis and access to appropriate care. HIV prevalence among Mozambican women aged 15-49 years is 15%, and vertical transmission rate is still high. The study investigated HIV exposure in children aged less than 2 years in Mozambique and the factors associated with unknown HIV exposure and with HIV exposure status in this population.

Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children.

Early initiation of antiretroviral therapy (ART) in vertically HIV-infected children limits the size of the virus reservoir, but whether the time of treatment initiation (TI) can durably impact host immune responses associated with HIV infection is still unknown. This study was conducted in PBMC of 20 HIV-infected virally suppressed children on ART (mean age 9.4 y), classified as early treated (ET; age at ART initiation ≤0.