"HBV unIversal vs Point-Of-Care-based Antiviral treatMent to Prevent Mother-to-child Transmission"

Summary

To achieve global elimination of hepatitis B virus (HBV), it is crucial to eliminate HBV mother-to-child transmission (MTCT) by ensuring high coverage of birth dose vaccine and expanding the adoption of peripartum antiviral prophylaxis (PAP) by tenofovir. Current international guidelines require hepatitis B surface antigen (HBsAg)-positive pregnant women to undergo viral load (VL) quantification to identify those at high risk (VL ≥200,000 IU/mL) who should receive PAP. However, VL testing remains inaccessible in many low- and middle-income countries (LMICs), particularly in rural areas. Consequently, in the forthcoming guidelines, the WHO is going to issue a conditional recommendation for administering PAP to all HBsAg-positive women lacking access to VL testing. Although this universal strategy may appear promising for simplifying the diagnostic process, it may result in overtreating the majority of HBsAg-positive pregnant women, estimated at 85% in Africa and 70% in Asia, for whom birth dose vaccine is likely sufficient. Moreover, the real-world applicability of this strategy in LMICs has never been formally tested.

As an innovative alternative, the adoption of a rapid point-of-care test for hepatitis B core-related antigen (HBcrAg-RDT) is proposed to identify women eligible for PAP.This test requires only a drop of capillary blood, eliminating the need for electricity or centrifugation, and can provide a reliable result within 45 minutes. Compared to the universal strategy, HBcrAg-RDT strategy is expected to be less expensive and could prevent unnecessary tenofovir exposure for both women and their fetuses. Our aim is to establish the non-inferiority of the HBcrAg-RDT strategy, in comparison to the universal strategy, in terms of effectiveness, defined as the reduction in maternal VL at the time of childbirth, a main driver of the MTCT risk. This will be approached through a multidisciplinary framework integrating health economics, implementation science, and health policy analysis.

Conditions

• HBV Infection
• Pregnancy

Interventions

DIAGNOSTIC_TEST

HBsAg RDT Women

HBsAg will be screened using finger-stick capillary blood during the ANC visit, simultaneously with the HIV test

DRUG

Treatment by TDF if HBcrAg RDT positive

300mg per day or 300 mg every 2 days (if créatinine clearance is 30-50ml/min)

DRUG

Treatment by TDF

300mg per day or 300 mg every 2 days (if créatinine clearance is 30-50ml/min)

OTHER

Social sciences component

The social sciences component only in Cambodia and Ivory Coast. 3 key sub-studies: i) a socio-economic and behavioral study ii) a health economic evaluation study, and iii) a health policy study. A mixed-methods approach will be used, including qualitative interviews and quantitative questionnaires among pregnant women and healthcare workers

DIAGNOSTIC_TEST

HBsAg RDT Infants

At 9 months, all infants will be tested for HBsAg; HBsAg-positive infants will undergo HBV DNA testing, and DBS will be collected for biobank storage.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France

  collaborator OTHER_GOV

• ANRS, Emerging Infectious Diseases

  lead OTHER_GOV

Principal Investigators

• Olivier SEGERAL · University Hospital, Geneva

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-11-30

Primary Completion

2026-11-30

Completion

2028-01-31