Increasing Neonatal HIV Test and Treat to Maximize the Long-Term Impact on Infant Health and Novel Infant Antiretroviral Treatment (LIFE2Scale)

This study aims to improve HIV healthcare services for mothers living with HIV and their newborns in Tanzania and Mozambique. The main questions it aims to answer are: 1) does enhancing screening with maternal HIV viral load monitoring at delivery identify more mother-child pairs at high-risk for HIV vertical transmission? and 2) are high-risk infants linked to appropriate prevention and care? The study will expand access to HIV testing services to more rural settings using a hub-and-spoke referral system.

Study Overview

• Status: Not yet recruiting
• Conditions: Infant, Newborn, Diseases; Infant Death; Infant Morbidity; Vertical Human Immunodeficiency Virus Transmission; HIV Infection Pediatric
• Intervention / Treatment: Procedure: Maternal HIV viral load testing at delivery for VHT risk assessment

Detailed Description

The UN Sustainable Development Goals set the ambitious goal to eliminate new paediatric HIV infections by 2030. Between 2010 and 2020, new HIV infections among children declined by more than 50%. This decline demonstrates the goal is achievable, but the loss of momentum in recent years indicates a need for further improvements. Results from the previous LIFE study conducted in Mozambique and Tanzania demonstrated that identifying HIV-infection in neonates and starting HIV treatment as early as birth is feasible and may reduce infant death and severe disease. However, this study also demonstrated that it is difficult to administer infant HIV treatments due to poor palatability of the infant drug formulation, socio-behavioural constraints for mothers, and care linkage challenges. This resulted in poor treatment adherence and efficacy (as measured by HIV suppression rates in the blood).

The investigators propose to expand and optimize treatment and prevention interventions for mothers living with HIV and their newborns and translate previous research findings into policy and practice, with a focus on primary healthcare to reduce access inequities in rural areas. The study aims to scale-up of tools used for vertical HIV transmission risk screening affiliated with immediate, risk-based HIV test & treat procedures. Testing for high-risk case detection will be implemented in a hub-and-spoke model, where smaller, less well-equipped health facilities refer samples to nearby larger health facilities for diagnostic testing, ensuring rural communities have access to the interventions. The investigators will also provide personnel support for scale-up of high-risk case detection and high-risk infant care management. Furthermore, all high-risk mother-baby pairs will receive enhanced counselling services. eHealth tools for electronic result sharing across health facilities will be part of our package of interventions.

The investigators will evaluate the impact of the intervention package described above on key prevention of vertical HIV transmission (PVHT) program indicators (e.g., percentage of high-risk newborns immediately tested for HIV, percentage of newborns with HIV immediately started on treatment) in a stepped-wedge, cluster-randomized study. The investigators will also conduct a cost-effectiveness analysis of the intervention package. Furthermore, the investigators will conduct interviews and use self-reported questionnaires by the participants and site staff to better understand the socio-economic and behavioural factors contributing to high-risk classification.

For HIV-positive babies, the investigators will assess the impact of a novel HIV drug used for newborns, i.e. Dolutegravir (DTG), on health outcomes. The investigators will also characterize the impact of transmitted and acquired genotypic drug resistance, as well as transmitted viral strains, towards neutralization against established and novel broadly neutralizing antibodies. This information will be used to inform future prevention and treatment strategies for HIV-exposed newborns.

All mothers of HIV-positive babies taking part in this study will continue to have access to enhanced counselling and care support throughout the study, and the investigators will collect information on socio-behavioural factors influencing treatment outcomes to understand challenges related to infant HIV treatment.

This study will be performed by an established consortium of interdisciplinary African and European experts, closely collaborating with health authorities and policy makers, thus ensuring effective and sustainable implementation, programmatic stewardship, and global access to the proposed complex intervention.

• Study Type: Observational
• Enrollment (Estimated): 6000

Contacts and Locations

• Study Contact: Name: Arne Kroidl, MD; Phone Number: 59816 +49-89-4400; Email: Arne.Kroidl@med.uni-muenchen.de
• Study Contact Backup: Name: Amy Heilman

Study Locations

• Mozambique
  • Beira, Mozambique
    • Centro de Investigacao Operacional de Beira (CIOB), Instituto Nacional de Saúde (INS), Ministério da Saúde,
    • Contact: Joaquim Lequechane
    • Principal Investigator: Ilesh Jani, MD, PhD
• Tanzania
  • Mbeya, Tanzania
    • National Institute for Medical Research (NIMR)
    • Contact: Issa Sabi, MD, PhD
    • Principal Investigator: Issa Sabi, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Pregnant women living with HIV and their exposed infants recruited at maternity clinics in Mozambique and Tanzania. The investigators expect to recruit 4000-6000 mother-child pairs in 12 months, or 56-71 mother-child pairs per cluster-randomization period (7 weeks) into Cohort A.

Assuming 12-week VHT rates of 2.5% and 1% VHT rates in Mozambique and Tanzania respectively, the investigators expect to roll-over approximately 105 HIV positive infants (75 in Mozambique and 30 in Tanzania) from both countries into Cohort B.

Description

Inclusion Criteria:

1. Voluntary and informed consent of the mother for her own study participation (if applicable);
2. Voluntary and informed consent of the legal guardian of the child for participation of the child in the study;
3. Mothers/legal guardians ≥18 years of age;
4. Documented maternal HIV infection;
5. Willingness to consent to HIV testing for the child and herself (or just her child); and

6. Willingness to consent to active tracing including home tracing.

   Exclusion Criteria:

7. Deficiency in the mother, rendering it difficult, if not impossible, for her or her infant to take part in the study or understand the information provided to her.
8. Having delivered more than 72h (3 days) ago;
9. Prisoners;
10. Women presenting with an emergency requiring immediate medical assistance if not resolved at study inclusion;
11. Stillbirths;
12. Infant requiring emergency care (e.g. immediate or rapid occurring life threatening conditions, resuscitation, prolonged obstetric related intensive care, severe jaundice) or born with severe malformation;
13. If within the discretion of the investigator based on recommendation of the gynaecologist or paediatrician in charge study participation would possibly add not acceptable risk or burden to the mother or infant (e.g. significant congenital malformation, health deficiencies, very low birth weight less than 1500g); or
14. Unlikely to comply with protocol as judged by the principal investigator or his designate

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A; HIV-exposed infants and their mothers enrolled in the study	Procedure: Maternal HIV viral load testing at delivery for VHT risk assessment; Maternal HIV viral load testing will be performed for all mothers enrolled in the study at delivery. Results will be used along with WHO-defined clinical criteria to determine risk status for VHT. The intervention also includes personnel to support the additional testing volume and management of high-risk cases and eHealth solutions for communication of test results between health facilities.
Cohort B; HIV-positive infants, identified in the first 12 weeks, and their mothers will be rolled over from Cohort A to Cohort B for long-term follow-up for up to 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of HIV-exposed infants correctly identified as low- or high-risk and receiving birth EID testing and ePNP or ART as appropriate within 7 days of life	All infants enrolled in the study: 1) assessed for high-risk criteria for VHT at birth, 2) if high-risk, receiving enhanced post-natal prophylaxis (ePNP) and PoC birth EID testing, AND 3) if HIV-positive, initiated on ART	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Turnaround times for EID testing at birth, 4-6 weeks, and 14 weeks (time from sample collection to receipt of results by the health facility and communication of results to the mother/caregiver) and maternal PoC VL testing at delivery and 14 weeks		14 weeks
Proportion and rate of VHT at birth, week 4-8, and week 14		14 weeks
Risk-factors associated with VHT	Demographic, socio-economic, and behavioral data collected from mothers	14 weeks
Adherence to PNP and ePNP		14 weeks
Proportion and rate of clinical endpoints (mortality, morbidity) among HIV-positive infants at week 14, month 6, and month 12		12 months
Age at ART initiation among HIV-positive infants		12 months
Risk factors for poor ART adherence among high-risk mothers and infants		12 months
Proportion of HIV-positive infants virally suppressed at week 14, month 6, and month 12		12 months
Risk factors for poor viral suppression among HIV-positive infants		12 months
Proportion of HIV-positive infants on ART that experience grade III or greater laboratory ART toxicity		12 months
Retention to HIV EID and infant health care services		14 weeks (Cohort A), 1 year (Cohort B)
Proportion of pregnant women presenting with criteria considered high-risk for VHT at delivery		7 days
Proportion of mothers virally suppressed at week 14 post-partum		14 weeks
Proportion and rate of post-partum mothers newly fulfilling high-risk criteria based on socio-behavioural criteria (i.e., adherence issues)		14 weeks
Characteristics of transmitted viral strains (lineages, subtypes, resistance mutations) among HIV-positive infants and in comparison to their mothers viral sequences	Mother-child comparative genomic analysis and virus quasi-species diversity (major/minor and transmitted strains)	12 months
Proportion of HIV-positive infants who develop acquired drug resistance mutations during the study		12 months
Characteristics of infant and maternal HIV strains to be neutralized against a panel of known broadly neutralizing antibody candidates (e.g., VRC07, 10-1074) and maternal autologous antibodies at time of transmission		12 months
Average public healthcare and healthcare-related expenditures		12 months
Average health worker time needed to care for mothers and infants per clinic visit, including for enhanced counselling sessions		12 months
Cost per HIV-exposed infant fulfilling the primary outcome		12 months
Empirical cost-effectiveness (incremental cost-effectiveness ratio) relating intervention costs to life-years saved among HIV-positive infants		12 months
Average global and dimensional patient satisfaction		14 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Hub-and-spoke model and provider satisfaction (health care personnel, focal point persons, counsellor)	12 months
Socio-behavioural and personal aspects related to high-risk criteria for mother-child pairs (adherence, retention, disclosure, emotional well-being and health care satisfaction)	14 weeks
Descriptions of tasks, functions, acceptability, challenge and workloads related to PVHT and neonatal HIV focal persons	12 months
Descriptions of tasks, functions, acceptability, challenge and workloads related to counsellors (enhanced high-risk counselling)	12 months
Description on eHealth functionality, satisfaction, acceptance of linkage procedures	12 months

Collaborators and Investigators

• Sponsor: Michael Hoelscher
• Collaborators: University of Liverpool; National Institute for Medical Research (NIMR) - Mbeya Medical Research Centre (MMRC); Instituto Nacional de Saúde (INS), Ministério da Saúde

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 24, 2024
• First Submitted That Met QC Criteria: February 12, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Prevention of Vertical HIV Transmission (PVHT); Infant HIV Prophylaxis; Early Infant HIV Diagnosis; Infant Antiretroviral Treatment
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Death; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Infant Death; Acquired Immunodeficiency Syndrome; Infant, Newborn, Diseases
• Other Study ID Numbers: LMU-IMPH-LIFE2Scale

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No