Efficacy of Tenofovir Disoproxil on Mother-to-child Transmission of HBV in Tokombéré, Cameroon in Pregnant Women

Phase 4RecruitingNCT05403047

ANRS, Emerging Infectious Diseases150 enrolled

Overview

Pregnant women with HBeAg-positive viral hepatitis b or high viral load will receive Tenofovir disoproxil fumarate (TDF) from the 28th week of amenorrhoea until 6 weeks after delivery. Their newborns will receive the hepatitis B vaccine, starting with one dose at birth and followed by three booster doses, according to the Expanded Programme on Immunisation. The investigators hypothesise that a short course of TDF could greatly reduce the risk of HBV MTCT in pregnant women at high risk of MTCT (HBeAg positive or with high viral load).

This is a prospective, single-arm, open-label, descriptive, phase IV clinical trial in HBsAg and HBeAg positive pregnant women. Eligible pregnant women will receive 245 mg of tenofovir disoproxil fumarate once daily from 28 weeks of pregnancy until 6 weeks after delivery. Newborns will receive the hepatitis B vaccine, starting with one dose at birth, followed by three booster doses, in accordance with the expanded programme of vaccination. The study aims to show that the addition of maternal antiviral treatment to vaccination at birth followed by three booster doses can be favourably considered in the context where vaccination alone is not sufficient to prevent transmission of the hepatitis B virus from mother to child. A total of 150 pregnant women will be included in the Tokombéré district.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

150

Conditions

Hepatitis B Virus - Chronic Active

Eligibility

Sex: FEMALEMin age: 16 Years

Medical Language ↔ Plain English

Inclusion criteria: * Pregnant women with a term of less than 24 weeks of amenorrhea; * HBsAg positive ; * HBeAg positive or HBeAg negative with a high viral load ( \> 200 000 UI/ml) ; * 16 years old or more on the inclusion day ; * Signature of free and informed consent (for pregnant women aged 16 to 21, the participant's consent as well as the authorization of a parent/adult husband/ legal tutor will be collected) which also includes consent for the children Exclusion criteria : * HIV co-infection; * Women treated for HBV; * Creatinine clearance \<30 ml / min; * Suspicion of poor monitoring of children's vaccination schedule for HBV (vaccination at birth + boosters); * Disease or treatment contraindicating the taking of TDF.

Outcomes

Primary Outcomes

Proportion of children with HBsAg positive at 9-12 months of life (W36 - W48) in the study population,

Proportion of HBsAg-positive children between 9 and 12 months of age in the study population, assessed by an automated test (mini VIDAS)

Time frame: measured between 36 and 48 weeks of life of the child of the mothers included in the study

Secondary Outcomes

Proportion of eligible women who accepted the intervention among eligible women offered the intervention (acceptance rate)

Proportion of women who took TDF continuously from the 7th month of pregnancy to 8 weeks postpartum (for at least 4 months) among women who accepted the intervention

Time frame: measured from 7 months of pregnancy to 8 weeks postpartum

Compliance with treatment

Compliance with treatment, estimated by self-report questionnaire and pill count

Time frame: from 28 weeks of pregnancy to 8 weeks postpartum

Progression of viral load

Progression of viral load, HBsAg, HBeAg, HBcr and anti-HBe seroconversion in pregnant women during the treatment period (measured at inclusion and at the end of the TDF treatment)

Time frame: measured from 24 weeks of pregnancy until the end of treatment

Estimate the protection rate of children with anti-HBs antibody level > 10 mIU/mL

Proportion of children with anti-HBs Ac \> 10 mIU/ml at 9-12 months / total number of children in the study.

Time frame: measured between 36 and 48 weeks of life of the child of the mothers included in the study

Assess the clinical and biological tolerance of TDF administration in mothers and children

Nature, number, frequency and intensity of adverse events in women; Nature, number, frequency, and intensity of adverse events in mothers and children and whether they are related to TDF use

Time frame: measured from 28 weeks of pregnancy until the end of treatment

Assess the rate of women requiring extended treatment after delivery

Proportion of cytolytic or virological rebounds (with detectable viral load) after cessation of treatment estimated by measurement of ALT and HBV viral load at 12 weeks and 24 weeks postpartum when they previously had a non-detectable viral load at 8 weeks postpartum

Time frame: Assess at 12 and 24 weeks postpartum

To assess the cost-effectiveness of the intervention (compared to vaccination alone, without hepatitis B immune globulin (Ig-anti HBV))

Incremental cost-effectiveness ratio of the intervention compared to the situation where children receive vaccination only (HBV vaccination at birth + pentavalent)

Time frame: To evaluate throughout the study