Arresting Vertical Transmission of Hepatitis B Virus

Study Overview
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Brief Summary
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The purpose of this pilot study is to demonstrate the feasibility of adding HBV screening and treatment of pregnant women to the existing HIV PMTCT platform in order to prevent mother-to-child transmission of hepatitis B virus.

Detailed Description
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Hepatitis B virus (HBV) is a leading cause of chronic liver disease globally, with devastating complications such as cirrhosis, hepatocellular carcinoma and death. Vertical transmission (VT) of HBV is a worldwide public health concern because infected children are at high risk of developing chronic liver disease. It is a particular problem in the Democratic Republic of the Congo (DRC); preliminary data suggest that approximately 3% of children have HBV infection due to VT. However, VT is preventable. Pregnant women with risk factors can be identified and treatments given which can virtually eliminate transmission. Unfortunately, despite the high burden of HBV, neither HBV testing of pregnant women nor interventions to prevent HBV VT are routinely performed in the DRC and elsewhere in sub-Saharan Africa. This pilot feasibility study will address this healthcare gap by identifying women with HBV early in their pregnancies and intervening to prevent VT by (1) treating mothers with high-risk HBV (defined as HBeAg positivity and/or HBV viremia >10^6) with tenofovir and (2) providing HBV vaccine to HBV-exposed infants within 24 hours of birth. This pilot study will piggyback onto an existing study that is evaluating the DRC's HIV Prevention of Maternal-to-Child Transmission Option B+ (PMTCT+) strategy. Combining programs to prevent VT of HBV and HIV enables using the same personnel and infrastructure to implement both interventions. Furthermore, tenofovir, used to treat HBV infections, is already used in the DRC to treat HIV. Researchers hypothesize that utilizing the existing PMTCT+ infrastructure in the DRC will provide a cost-effective platform to prevent HBV VT. If effective, this model of treatment will inform future public health efforts and wider policy recommendations that can be applied in the DRC and throughout the Sub-Saharan African region to reduce the burden of HBV.

Official Title
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Arresting Vertical Transmission of Hepatitis B Virus in the Democratic Republic of the Congo: The AVERT-HBV Study

Conditions
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Hepatitis B, Vertical Transmission of Infectious Disease

Intervention / Treatment
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* Drug: Tenofovir Disoproxil Fumarate
* Biological: Monovalent HBV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Pregnant women receiving care at Binza and Kingasani maternity centers presenting prior to 24 weeks gestation Infants born to HBV-positive women Exclusion criteria: Participants who are severely sick and who require prolonged hospitalization. Any women who do not intend to stay in Kinshasa for prenatal care through delivery
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-risk HBV dyads<br>Mothers with high-risk HBV (defined as viral load >10^6 and/or HBeAg positivity) will be treated with tenofovir disoproxil fumarate (TDF) to further reduce the risk of vertical transmission of HBV. All HBV-exposed infants (regardless of mother's status of high- or low-risk HBV) will receive monovalent HBV vaccine within 24 hours of life. | Drug: Tenofovir Disoproxil Fumarate<br>* 300 mg tablet of TDF once daily from 28-32 weeks gestation through 12 weeks postpartum.<br>* Other names: Viread;Biological: Monovalent HBV vaccine<br>* Infants born to HBsAg-positive women will be given a single dose of monovalent HBV vaccine within 24 hours of life.<br>* Other names: Engerix-B;|
| Experimental: Low-risk HBV dyads<br>Mothers with low risk HBV (defined as a viral load <10^6 and negative HBeAg) will not receive tenofovir disoproxil fumarate therapy during or after pregnancy. Their infants will still receive monovalent HBV vaccine within 24 hours of life. | Biological: Monovalent HBV vaccine<br>* Infants born to HBsAg-positive women will be given a single dose of monovalent HBV vaccine within 24 hours of life.<br>* Other names: Engerix-B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Lab Testing Acceptability Survey Scores >80% | The acceptability of laboratory testing approach to participants will be defined as >80% acceptability on a two questions each measured using a 5-point Likert scale (range 1-5, highest score of 5 representing the highest acceptability). For example, the options for participant responses will include: Very unacceptable (1), Somewhat unacceptable (2), No opinion (3), Somewhat acceptable (4), Very acceptable (5) and Did not allow study personnel to take my blood. Scores equal to or greater than 4 considered 80%. | Upon completion of the exit survey, or up to 12 months | 
| Number of Mothers With Infant Vaccination Acceptability Survey Scores >80% | The acceptability of the intervention approach to participants will be defined as >80% acceptability on a single question measured using a 5-point Likert scale (range 1-5, highest score of 5 representing the highest acceptability). For example, the options for responses will include: Very unacceptable (1), Somewhat unacceptable (2), No opinion (3), Somewhat acceptable (4), Very acceptable (5) and Did not allow study personnel to vaccinate my infant. Scores equal to or greater than 4 considered 80%. | Upon completion of the exit survey, or up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Infants With HBV Positivity at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV | Mother-to-child transmission of HBV is defined as HBsAg positivity in the infant at 6 months of life. | Measured at 6 months after birth | 
| Number of Mothers With High-risk HBV Demonstrating Adherence to Tenofovir Therapy | Adherence to tenofovir therapy is defined as <20% of pills remaining on monthly pill counts for high-risk mothers with HBV receiving tenofovir | Pill counts to be measured monthly. Total adherence averaged over 6-month treatment period. | 
| Number of Infants Receiving Timely Birth Dose Vaccination | Timeliness of infant HBV vaccination is defined as >90% of infants receiving birth dose vaccine within 24 hours of life | Within 24 hours after birth |