HIPOCAMP: universal prophylaxis vs prophylaxis against perinatal transmission of the hepatitis B virus

Background to the HIPOCAMP project

To achieve the global elimination of hepatitis B, it is essential to eliminate mother–to–child transmission (MTCT) of the virus. This rests on three pillars: screening of pregnant women, good vaccination coverage with a dose at birth, and access to peripartum antiviral prophylaxis (PAP) using tenofovir disoproxil fumarate (TDF).

Mother-to-child transmission remains a major public health problem in low- and middle-income countries, as a significant proportion of chronic infections are acquired at birth or in early childhood. Without intervention, the risk of transmission is particularly high among mothers with a high viral load, and children infected at birth go on to develop chronic infection in approximately 90 per cent of cases.

The World Health Organisation (WHO) recommendations stipulate that pregnant women who test positive for hepatitis B surface antigen (HBsAg) should undergo viral load (VL) testing to identify those at high risk of transmission (VL ≥ 200,000 IU/mL), who are eligible for pre-delivery prophylaxis (PAP). However, this test remains inaccessible in many decentralised, resource-limited settings, where it requires a fully equipped laboratory, a specimen transport chain and turnaround times that are often incompatible with antenatal care.

In response to this challenge, the WHO issued a conditional recommendation in 2024: to administer tenofovir to all HBsAg-positive pregnant women when viral load measurement or the hepatitis B e-antigen (HBeAg) test are not available. This universal strategy could broaden access to prevention and simplify care. However, it would result in the majority of HBsAg-positive women who are not at high risk being treated, even though vaccination at birth is likely to be sufficient for them. Furthermore, its feasibility, acceptability and cost-effectiveness in these settings have never been assessed.

An innovative alternative: a rapid point-of-care test

To target prophylaxis without relying on a laboratory, the HIPOCAMP project proposes using the ESPLINE™ HBeAg-hs rapid test as a highly sensitive rapid test for the detection of the HBe antigen – a new rapid (point-of-care) test approved by the European Commission and validated by the project teams. This test requires only a single drop of capillary blood, needs neither electricity nor centrifugation, and provides a result in under an hour, during the antenatal consultation. Compared with the universal strategy, a targeted strategy based on this test is expected to be less costly and to avoid unnecessary exposure to tenofovir for women and their foetuses.

Objectives and methodology of the HIPOCAMP project

The ANRS 0562s HIPOCAMP study is a multicentre, cluster-randomised, two-arm trial designed to demonstrate the non-inferiority of the targeted strategy compared with the universal strategy. It is coordinated by Yusuke Shimakawa (Institut Pasteur), Didier Ekouevi (University of Lomé) and Olivier Ségéral (Geneva University Hospitals), and is being conducted in four countries: Cameroon, Côte d’Ivoire and Togo in Africa, and Vietnam in Asia.

A total of 3,200 HBsAg-positive pregnant women will be enrolled and followed up for up to nine months after delivery. Two prevention strategies will be compared:

• Universal strategy: all HBsAg-positive women receive tenofovir prophylaxis;
• Targeted strategy: only women identified as high-risk by the HBcrAg rapid test receive treatment.

The primary outcome measure is efficacy, defined as the suppression of maternal viral load at the time of delivery – the main determinant of mother-to-child transmission – whilst ensuring that women remain in care. Secondary endpoints include HBV infection in infants, treatment tolerability, adherence, cost-effectiveness, implementation indicators and linkage to postnatal care.

A multidisciplinary approach

Beyond the clinical trial, HIPOCAMP adopts a multidisciplinary approach integrating health economics, implementation science and health policy analysis. The project will examine the feasibility and acceptability of each strategy in different countries, as well as the perceptions of women and healthcare professionals. A qualitative component will focus on women’s lived experiences and their perceptions of each approach. The health economic analysis will compare the costs and benefits of the two strategies, whilst the analysis of national policies will help to identify the conditions necessary for integrating the most appropriate strategy into health programmes and scaling it up.