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

Michael Hoelscher

Status: Enrolling

Conditions: Infant Death; Vertical Human Immunodeficiency Virus Transmission; HIV Infection Pediatric; Infant, Newborn, Diseases; Infant Morbidity

Treatments: Procedure: Maternal HIV viral load testing at delivery for VHT risk assessment

Study type: Observational

Funder types: Other

Identifiers

NCT06267508

LMU-IMPH-LIFE2Scale

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6,000 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

6,000 participants in 2 patient groups

Cohort A

Description:

HIV-exposed infants and their mothers enrolled in the study

Treatment:

Procedure: Maternal HIV viral load testing at delivery for VHT risk assessment

Cohort B

Description:

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.