About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
≥18 years old, or ≥ the legal age of majority as defined by each country, on the day of inclusion.
Pregnancy.
Intention to attend antenatal care visits in the Primary Health Center or the Rural Hospital
Living in an area covered by the Primary Health Center or the Rural Hospital on the start date of the trial
Disqualifiers
HIV co-infection.
HBV treatment ongoing on the day of inclusion.
Severe gravid disease at inclusion, which poses a life-threatening risk to the mother and/or child
Any concomitant medical condition that, according to the clinical site investigator, would contraindicate participation in the study.
Trial design
Parallel
Treatments tested in this trial
HBsAg RDT Women
Diagnostic testHBsAg will be screened using finger-stick capillary blood during the ANC visit, simultaneously with the HIV test
Treatment by TDF if HBcrAg RDT positive
Drug300mg per day or 300 mg every 2 days (if créatinine clearance is 30-50ml/min)
Treatment by TDF
Drug300mg per day or 300 mg every 2 days (if créatinine clearance is 30-50ml/min)
Social sciences component
Other interventionThe 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
HBsAg RDT Infants
Diagnostic testAt 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.
Treatment groups
Trial outcomes
Primary outcomes
Percentage of HBsAg-positive women with HBV DNA <200,000 IU/mL at the time of delivery
The primary endpoint will be the percentage of HBsAg-positive women who present at healthcare facilities for delivery and have an HBV DNA \<200,000 IU/mL at the time of delivery.
Secondary outcomes
Percentage of infants positive for HBsAg
Other outcomes
Percentage of women eligible for PAP who started TDF
Percentage of women eligible for PAP who completed TDF prophylaxis
Percentage of women with adherence >90% at each study visit based on pill counts and self-report
Percentage of infants receiving HepB-BD
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
ANRS, Emerging Infectious Diseases
Lead sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Collaborator