Clinical trial NCT03567382
Conditions: Hepatitis B Vertical Transmission of Infectious Disease
Sponsor: University of North Carolina, Chapel Hill
Start date: 2018-09-24; Completion date: 2020-08-15
Enrollment: 179 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
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:
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.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Tenofovir Disoproxil Fumarate intervention 2: Monovalent HBV vaccine
Intervention descriptions: intervention 1: 300 mg tablet of TDF once daily from 28-32 weeks gestation through 12 weeks postpartum. intervention 2: Infants born to HBsAg-positive women will be given a single dose of monovalent HBV vaccine within 24 hours of life.

Protocol documents:
Prot_SAP_000.pdf: 
 
Prenatal Treatment to Prevent Mother to Child Transmission of 
Hepatitis B Virus in the DRC: The Arresting Vertical Transmission of 
Hepatitis B (AVERT-HBV) Study 
 
 
 
NCT number NCT03567382 
Document Date 12/06/2018 
 


 
 
 
Peyton Thompson, MD, MSCR 
111 Mason Farm Rd, 2336 MBRB 
CB#7036 
Chapel Hill, NC 27599 
email: peyton_thompson@med.unc.edu 
 
PROTOCOL TITLE:  
Prenatal Treatment to Prevent Mother to Child Transmission of Hepatitis B Virus in the 
DRC: The Arresting Vertical Transmission of Hepatitis B (AVERT-HBV) Study 
Short Title:  
AVERT-HBV 
Lead Investigator: 
Peyton Thompson, M.D., MSCR 
 University of North Carolina at Chapel Hill 
Protocol Version: 1.4 
Version Date: December 6, 2018 
 
I confirm that I have read this protocol and understand it.    
Principal Investigator Name:   
 
 
 
 
 
 
 
Principal Investigator Signature:  
 
 
 
 
 
 
 
Date:   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
2 
TABLE OF CONTENTS 
Table of Contents .............................................................................................................. 2 
Abbreviations and Definitions of Terms ............................................................................ 3 
Protocol Synopsis ............................................................................................................. 4 
1 BACKGROUND  AND RATIONALE ...................................................................................... 8 
2 STUDY OBJECTIVES ......................................................................................................... 10 
3 INVESTIGATIONAL PLAN ................................................................................................. 10 
4 STUDY PROCEDURES ...................................................................................................... 12 
5 STUDY EVALUATIONS AND MEASUREMENTS ................................................................. 14 
6 STATISTICAL CONSIDERATIONS ...................................................................................... 15 
7 STUDY INTERVENTION (DEVICE OR OTHER INTERVENTION) .......................................... 16 
8 SAFETY MANAGEMENT .................................................................................................. 17 
9     DATA COLLECTION AND MANAGEMENT ....................................................................... 17 
10 RECRUITMENT STRATEGY ............................................................................................... 18 
11 CONSENT PROCESS ......................................................................................................... 18 
12 PUBLICATION ................................................................................................................. 18 
13 REFERENCES ................................................................................................................... 19 
Appendices………………………………………………………………………………………………………………………..20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
3 
 
ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
 
 
Abbreviation 
Definition 
DBS 
Dried blood spot 
DRC 
Democratic Republic of the Congo 
HBeAg 
Hepatitis B e antigen 
HBIG 
Hepatitis B immunoglobulin 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HBV DNA 
Hepatitis B viral load 
MCH 
Maternal and child health 
MTCT 
Mother-to-child transmission 
PMTCT 
Prevention of mother-to-child transmission 
VT 
Vertical transmission 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
4 
 
 
 
PROTOCOL SYNOPSIS 
 
Study Title 
Prenatal Treatment to Prevent Mother to Child Transmission of 
Hepatitis B Virus in the DRC: The Arresting Vertical Transmission of 
Hepatitis B (AVERT-HBV) Study 
 
Funder 
Gillings Innovation Labs 
Clinical Phase 
N/A 
Study Rationale 
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); our 
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. Our 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 >106) with tenofovir +/- lamivudine and (2) providing HBV 
vaccine to HBV-exposed infants within 24 hours of birth. Our 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 and 
lamivudine, used to treat HBV infections, are already used in the DRC 
to treat HIV. We 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. 


 
5 
Study Objective(s) 
Specific Aim 1: Conduct a pilot feasibility study of two-step HBV 
prenatal screening for HBV infection among pregnant women 
in the DRC. We will screen 4,000 pregnant women with HBV 
rapid diagnostic testing (HBV surface antigen [HBsAg]) and will 
identify a subset of women with high-risk disease by evaluating 
viral loads and HBV e antigen (HBeAg) performed on both venous 
blood and dried blood spots. The major outcome of this aim will 
be the feasibility of this testing strategy: acceptability to patients 
and staff, collection of samples, and time from sample collection 
to results. Other outcomes will include the test characteristics of 
these studies (sensitivity, specificity, positive predictive value 
and negative predictive value to assess agreement between 
dried blood spot (DBS) and gold standard venous blood 
sampling) and the cost of adding them to the existing PMTCT 
program.  
 
 
Specific Aim 2: Conduct a pilot feasibility study of an 
intervention program to prevent HBV VT.  We anticipate 
screening 4,000 pregnant women for HBV, of whom we expect 
that 2.5% (100) will have positive HBV testing. Of these 100, we 
expect 30-50% (30-50 women) to have high-risk disease (defined 
as positive HBeAg and/or HBV viremia >106) and to therefore 
require prophylactic antiviral therapy with tenofovir +/- 
lamivudine. A small subset of women who are HIV-positive (an 
estimated 3-5 women) will receive tenofovir and lamivudine as 
part of their HIV treatment, and so will not receive it as part of 
this study. All HBV-exposed infants will receive HBV vaccine 
within 24 hours of delivery. If successful, this model could be 
easily exported to other countries in sub-Saharan Africa. The 
major outcomes of this aim are (1) adherence to treatment; (2) 
acceptability of antiviral therapy; (3) maternal HBV viral load at 
delivery and 24 weeks post-partum and (4) infant HBsAg at 24 
weeks post-partum; and (5) additional cost to the existing 
PMTCT program. 
Test Article(s) 
(If Applicable) 
Tenofovir +/- lamivudine 
Monovalent HBV vaccine 
Study Design 
 
This pilot feasibility study will involve identification of a cohort of  
HBV-infected pregnant women and their infants, who will receive 
proven interventions to prevent vertical transmission of HBV in a 
resource-poor setting. Of 4,000 women screened for HBV with 
HBsAg, we expect 100 (2.5%) to have positive testing. The HBsAg-
positive participants will undergo further testing with HBV viral 
load and HBeAg to identify those at high risk of transmission 
(positive HBeAg and/or HBV viremia >106). We expect 30-50 
women to be categorized as high-risk. Women with high-risk HBV 


 
6 
will be treated with prophylactic tenofovir +/- lamivudine starting 
at 28-32 weeks’ gestation and continuing through 12 weeks’ 
postpartum. A small subset of these women (3-5) will be co-
infected with HIV, and so will already be receiving tenofovir and 
lamivudine as part of their HIV therapy. HIV-negative women with 
low-risk HBV will not receive antiviral therapy, but will undergo the 
similar testing procedures as those with high-risk HBV. All HBV-
exposed infants will receive a monovalent HBV vaccine dose within 
24 hours of life and their HBV status will be assessed at 24 weeks. 
Subject Population 
key criteria for Inclusion 
and Exclusion: 
Inclusion criteria: 
• Pregnant women receiving care at Binza and Kingasani 
maternity centers who present prior to 24 weeks gestation 
• Infants born to HBV-positive women will be included in the 
study 
Exclusion criteria: 
• The study will not enroll 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 
 
Number Of Subjects  
 
 4,100 (4,000 pregnant women screened in order to enroll 100 
HBsAg+ women and 100 HBV-exposed infants) 
Study Duration 
Participation of mothers will last for up to 12 months and that of 
infants will last 6 months.  
The entire study is expected to last for 2 years. 
Study Phases 
Screening 
Study Treatment 
Follow-Up   
(1) Screening: Consent and screening for HBV 
(HBsAg).Determination of HBV risk status among HBsAg-
positive women. 
(2) Intervention: Antiviral prophylaxis for HIV-negative pregnant 
women with high-risk HBV. Vaccination of HBV-exposed 
infants. 
(3) Follow-up:  Repeat laboratory testing of mothers at delivery, 
and at 10 and 24 weeks’ postpartum. Exit interview for 
mothers at 6 months postpartum. Laboratory testing of 
infants at 6 months of life. 
Efficacy Evaluations 
Feasibility of the study, as determined by responses to 
questionnaires by study participants and research personnel. 
Additional costs to HIV PMTCT program. Loss-to-follow-up of 
study participants. Rate of MTCT of HBV. Comparison of HBV test 
characteristics for DBS versus venous blood sampling. 


 
7 
Safety Evaluations 
Adverse effects of tenofovir, lamivudine and/or monovalent HBV 
vaccine 
Statistical And Analytic 
Plan 
For specific aim 1, we will determine the feasibility of the testing 
strategy by measuring the following: acceptability to patients and 
staff, ease of sample collection and transport, and time from 
sample collection to results. Secondary measures will be the 
agreement of test characteristics (sensitivity, specificity, positive 
predictive value and negative predictive value of (1) HBeAg and 
(2) HBV viral loads) between DBS and gold standard venous blood 
sampling. If agreement is demonstrated, DBS testing is a more 
cost-effective manner for such testing in low-resource areas. We 
will also determine the additional costs of HBV screening to the 
PMTCT+ program. For specific aim 2, we will measure how many 
and when women and their infants are lost to the treatment 
cascade; the percentage of women with highly active HBV who 
receive antiviral treatment and who achieve reduction or 
suppression of HBV viremia, the development of ALT elevation 
during or after treatment, and resolution of e antigen positivity; 
loss-to-follow-up (LTFU, percentage of women who are initiated 
on antiviral treatment but are not able to complete the 
recommended course) and adherence to tenofovir +/- lamivudine 
and vaccination; and the rate of mother-to-child transmission 
(MTCT) of HBV, defined as the proportion of infants born to HBV-
positive mothers who test positive for HBV. 
DATA AND SAFETY 
MONITORING PLAN 
PI, co-investigators and research coordinators in Kinshasa will be 
responsible for data quality management and ongoing 
assessment of safety. Data will be gathered in the form of paper 
charts and questionnaires. Study site supervisors will check paper 
forms for completeness and consistency, and will enter the 
completed forms into the electronic database (Access or EpiData). 
The research team at UNC will upload data on a biweekly basis to 
conduct quality assurance.  
Safety monitoring will occur on an ongoing basis by the Kinshasa-
based study team, and any concerns will be reported to the study 
physician. Monitoring by the PI and co-investigators will occur on 
a monthly basis. While the likelihood of terminating the study 
early due to safety concerns is minimal, study personnel will 
consider this if there is a high frequency of safety concerns related 
to antiviral therapy. 
 
 
 
 
 


 
8 
 
1 
BACKGROUND AND RATIONALE 
HBV is a major cause of chronic liver disease, liver cancer, and death worldwide.  Despite the presence of 
effective vaccines and antivirals, there are still more than 300,000 deaths each year from HBV-related 
cirrhosis and an equal number of deaths due to HBV-induced liver cancer.1 The burden of HBV is highest in 
Southeast Asia as well as the sub-Saharan region of Africa in countries like the DRC. 
 
HBV is highly transmissible and is commonly spread from mother to infant by vertical transmission (VT).  Since 
there is a 90% chance that chronic infection will develop in vertically infected children, interventions that 
prevent HBV VT offer tremendous public health value by reducing overall infections and minimizing the pool of 
individuals that could spread HBV to others later in life.2,3  Through existing collaborations with the DRC Ministry 
of Health (MOH) and Abbott Laboratories and a new collaboration with Ohio State University, we will conduct 
the Arresting Vertical Transmission of HBV (AVERT-HBV) study.   
 
At the request of the DRC Ministry of Health, we recently established a collaboration with Abbott Laboratories 
to estimate the prevalence of viral hepatitis in the DRC.  We are testing dried blood spots collected from subjects 
enrolled in the 2013-2014 DRC Demographic and Health Survey (DHS), a national population-based survey 
conducted by MEASURE-DHS (ICF International, Rockville, MD). Our preliminary data indicated that 3.3% of 
children ≤5 years of age in the DRC are HBV DNA positive, most likely as a result of VT.  
 
When a pregnant woman has HBV infection, the risk of VT can be reduced by 90% when vaccine coupled with 
HBV Immune Globulin (HBIG) are administered to the infant at birth.2,3 HBIG is not a part of standard World 
Health Organization (WHO) guidelines due to its limited availability and is not currently accessible in the DRC, 
but HBV vaccine and HBV antiviral supply lines are well-established.4 While the HBV vaccine is part of the DRC’s 
Expanded Program on Immunization (over 70% of DRC infants completed a 3-dose HBV vaccination series 
country-wide),5 it is not administered until the child is 6 weeks old, outside of the 24-hour window 
recommended for the prevention of VT. The present study seeks to leverage existing infrastructure to address 
HBV VT in the DRC with available tools. It is clear that a new approach to infant HBV vaccination is needed in 
order to reduce the very high ongoing and future burden of HBV in the DRC.  
 
Even with HBV vaccination, infants born to high-risk women, with high-level HBV DNA viremia (>106 IU/mL) 
and/or HBeAg positivity, remain at high risk for breakthrough transmission.6-8 The standard of care in the US 
and other parts of the world is to initiate antiviral therapy with tenofovir and/or lamivudine among high-risk 
mothers during pregnancy.  This reduces HBV viral loads by >3-4 logs and subsequently minimizes the risk of 
HBV VT.9 This screening and intervention works and has been codified into U.S. guidelines for care,4,11 but it has 
not been implemented in the DRC, where the burden is high. 
 
In this project, we propose to capitalize on existing infrastructure in the DRC to screen for HBV early in gestation 
and initiate treatment. This intervention has the potential to reduce breakthrough cases of HBV VT by 60-
90%,9,12 which would lead to health benefits of reduced cirrhosis and liver cancer that would last years into the 
future. 
 
1.1 
Introduction 
Study enrollment will take place in two antenatal clinics located in Kinshasa Province that have ongoing PMTCT 
programs for prevention of VT of HIV. Our collaborator, Dr. Yotebieng (who received his PhD at UNC) has an 
ongoing study of the PMTCT program at both centers (NIH R01HD087993). Approximately 500 pregnant women 


 
9 
in his study underwent HBsAg testing, and 5% were HBV-positive. We will screen 2,000 pregnant women for 
HBV, and expect 100 women to have positive HBV testing.  
1.2 
Name and Description of Investigational Product or Intervention  
Pregnant women with high-risk HBV infection will receive antivirals as prophylactic therapy starting at 28-32 
weeks’ gestation and continuing through 12 weeks’ postpartum. Both tenofovir and lamivudine are key 
components of highly-active antiretroviral therapy (HAART) for HIV. Therefore, the mothers who are HIV-HBV 
co-infected will receive it as part of their HAART therapy and will not require additional treatment for HBV. 
Mothers with high-risk infection who are HBV mono-infected, however, will require tenofovir +/- lamivudine 
initiation as part of our study intervention to prevent VT of HBV. 
Infants in the DRC normally receive a pentavalent vaccine including HBV at 6 weeks of life. For HBV-exposed 
infants in our study, we will provide a birth dose of monovalent HBV vaccine in addition to the regularly 
scheduled HBV doses (at 6, 10 and 14 weeks). 
1.3 
Non-Clinical and Clinical Study Findings 
The determination of the prevalence of HBV infection among pregnant women in Kinshasa Province, DRC will 
contribute to knowledge about the burden of disease and need for interventions. The combination of antiviral 
therapy administered to pregnant women at high risk for VT of HBV and vaccination of their infants within 24 
hours of life has the potential to substantially reduce the burden of chronic HBV infection in high-burden 
countries like the DRC. While most countries in sub-Saharan Africa already have the PMTCT infrastructure in 
place for the delivery of these interventions, the implementation of these interventions has yet to be 
integrated into routine care settings. Pending success of our model of care, we anticipate that this framework 
will inform the development of guidelines on how to integrate these interventions into the public health 
system throughout sub-Saharan Africa.  
Potential benefits of this study are the interruption of MTCT of HBV. Risks are associated with blood sample 
collection, vaccination and tenofovir treatment. The study will require blood collection from infants via heel 
prick, which is painful but less so than a venous blood collection. Vaccination will cause minimal discomfort to 
infants. There is a possibility for an adverse reaction to the HBV vaccine, in which case study personnel will 
clearly document the reaction and the infant will be closely monitored. Infants delivered at the maternity 
health centers are not sent home with their mothers until day 2 or 3 of life, so there will be adequate time to 
observe the infants after vaccination. Previous studies have demonstrated minimal risk to fetuses exposed to 
tenofovir (TDF) and lamivudine, with rates of birth defects similar among treatment and control groups.9,10 
While TDF and 3TC therapy has not been associated with harm to the fetus, the main concern among mothers 
is the development of immune-active hepatitis in the post-partum period after discontinuation of tenofovir. In 
the study by Pan et al, statistically significant elevations in alanine aminotransferase (ALT) levels were seen 
after discontinuation of TDF in the treatment arm compared with the control arm. Our study will routinely 
monitor mothers in the post-partum period after discontinuation of antivirals for elevations in liver enzymes, 
and will refer mothers with active hepatitis to our study gastroenterologist. The benefit of treatment – 
prevention of VT of HBV – far outweighs the potential risk to mothers of the development of immune-active 
hepatitis after treatment. Based on previous studies cited above, there is minimal risk to the fetus involved in 
maternal treatment with tenofovir +/- lamivudine. 
 
1.4 
Relevant Literature and Data 


 
10 
1   Stanaway JD, Flaxman AD, Naghavi M, et al. The global burden of viral hepatitis from 1990 to 2013: findings 
from the global Burden of Disease Study 2013. Lancet 2016;388(10049):1081-1088. 
2   Mast EE, Margolis HS, Fiore AE, et al. Advisory Committee on Immunization Practices. A comprehensive 
immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: 
recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of 
infants, children and adolescents. MMWR Recomm Rep. 2005;54(RR-16):1-31. 
3   André FE, Zuckerman AJ. Review: protective efficacy of hepatitis B vaccines in neonates. J Med Virol. 
1994;44(2):144-151. 
4   World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic 
hepatitis B infection.              Published March 2015. Available at: 
http://apps.who.int/iris/bitstream/10665/154590/1/9789241549059_eng.pdf Accessed 9 May 2017. 
5   World Health Organization. Democratic Republic of the Congo: WHO and UNICEF estimates of 
immunization coverage. Published 2015. Available at: 
http://www.who.int/immunization/monitoring_surveillance/data/cod.pdf Accessed 23 January, 2017. 
6   Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active 
immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012;19(2):e18-25.  
7   Song YM, Sung J, Yang S, Choe YH, Chang YS, Park WS. Factors associated with immunoprophylaxis failure 
against vertical transmission of hepatitis B virus. Eur J Pediatr 2007;166:813-818. 
8   Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. 
Pediatrics 2015;135(5):e1141-e1147. 
9   Pan CQ, Duan Z, Dai E, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. 
NEJM 2016;374(24):2324-2334.  
10 Brown RS, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during 
pregnancy: A systematic review and meta-analysis. Hepatology 2016;63(1):319-33.) 
11 Terrault NA, Bzowej NH, Chang K, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 
2016;63(1):261-283. 
12 Chen HL, Lee CN, Chang CH et al. Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-
to-infant transmission of hepatitis B virus. Hepatology 2015;62:375-86. 
 
2 
STUDY OBJECTIVE  
This pilot feasibility study of HBV-infected pregnant women in the DRC will allow for early identification and 
treatment of HBV-positive pregnant women and their newborns in order to reduce maternal-to-child 
transmission of HBV. 
2.1 
Specific Aim 1 
Conduct a pilot feasibility study of two-step HBV prenatal screening for HBV infection among pregnant 
women in the DRC. We will screen 4,000 pregnant women with HBV rapid diagnostic testing (HBV surface 
antigen [HBsAg]) and will confirm the results with viral loads and HBV e antigen (HBeAg) testing performed on 
both venous blood and dried blood spots. We expect 100 women (2.5%) to have positive HBsAg testing, and 30-
50 to have high-risk disease (defined as positive HBeAg and/or HBV viremia >106). The major outcome of this 
aim will be the feasibility of this testing strategy: acceptability to patients and staff, collection of samples, and 
time from sample collection to results. Other outcomes will include an analysis of agreement between test 
characteristics (sensitivity, specificity, PPV and NPV) for HBeAg and HBV DNA testing of DBS samples compared 
to the gold standard of venous blood sampling, and the cost of adding them to the existing PMTCT program.  
 


 
11 
2.2 
Specific Aim 2 
Conduct a pilot feasibility study of an intervention program to prevent HBV VT.  We anticipate screening 4,000 
pregnant women for HBV infection, of whom we expect that 2.5% (100) will have positive HBV testing. HIV-
negative women identified as having high-risk disease (defined as HBeAg positivity and/or HBV viremia >106) 
will be given prophylactic tenofovir +/- lamivudine starting at 28-32 weeks’ gestation and continuing through 12 
weeks’ postpartum. A subset of these women (an estimated 3-5 women) who are HIV-positive will already be 
receiving tenofovir and lamivudine as part of their HIV therapy. HIV-negative women with low-risk HBV will 
undergo routine HBV testing but will not receive antiviral therapy. All infants born to HBV-positive women will 
be enrolled in the study and will receive HBV vaccine within 24 hours of life. If successful, this model could be 
easily exported to other countries in sub-Saharan Africa. The major outcomes of this aim are (1) adherence to 
treatment; (2) acceptability of treatment by pregnant women; (3) maternal HBV viral load at delivery and 24 
weeks post-partum and (4) infant HBsAg at 24 weeks post-partum; and (5) additional cost to the existing PMTCT 
program. 
 
 
3 
INVESTIGATIONAL PLAN (brief overview) 
3.1 
Study Design 
Type of design: pilot feasibility study 
This is a cohort study of pregnant women and their infants who will receive a package of proven interventions 
to prevent vertical transmission of HBV in a resource-limited setting. It is not a clinical trial. The purpose of the 
study is to prove the feasibility of testing and treatment for HBV among pregnant women in the DRC using the 
HIV PMTCT framework. 
After the study is described to participants and verbal consent is obtained, pregnant women will be screened 
for HBV with HBsAg testing. Formal written consent will be obtained for those with positive HBsAg testing. We 
anticipate screening 4,000 pregnant women, of whom we expect 100 (2.5%) to have positive HBV testing. 
Screening may end prematurely if 100 HBV-positive women are identified prior to reaching the anticipated 
number of 4,000. Based on rates of HBV positivity of 5% in the ongoing HIV PMTCT+ study, we anticipate being 
able to enroll 100 HBV-positive women. However, if 2,000 women are screened and the number of HBV-
positive participants falls below 100, the study will continue to screen additional participants until 100 HBV-
positive women are identified. Because of an actual HBsAg prevalence of 2.8%, we are increasing the 
number of anticipated participants for screening to 4,000 in order to reach a goal of 100 HBsAg+ enrollees. 
The HBV-positive mothers will be sub-divided into those with high-risk HBV (defined as HBeAg positivity 
and/or HBV viremia >106) versus low-risk HBV. HBV mono-infected women with low-risk disease will undergo 
additional laboratory testing as outlined in study procedures, but will not be treated with antivirals during 
pregnancy.  HBV mono-infected women with high-risk disease will receive tenofovir +/- lamivudine as 
prophylactic therapy starting at 28-32 weeks’ gestation and continuing through 12 weeks’ postpartum. The 
small subset of HIV-HBV co-infected mothers will already be receiving tenofovir and lamivudine as part of their 
HIV therapy. Mothers will be followed at enrollment, 2-4 weeks after enrollment, at routine antenatal visits, at 
delivery, and at 10 and 24 weeks postpartum. 
Appendix B outlines the study design, from initial screening through final study visit. 


 
12 
All infants born to HBV-infected mothers will be given a birth dose of monovalent HBV vaccine within 24 hours 
of life. Infants will be enrolled at birth and followed at 10 weeks and 24 weeks. 
3.2 
Study Duration, Enrollment and Number of Subjects 
The entire study is expected to last 3.5 years (1 year of enrollment, 1.5 years of follow-up, and 1 year for data 
analysis).  
Enrollment of individual mothers will be a maximum of 12 months (as early as 12 weeks’ gestation through 24 
weeks postpartum). Infants will be enrolled for a total of 6 months.  
We expect to enroll a total of 4,100 subjects, including 4,000 pregnant women for screening in order to enroll 
100 HBsAg+ pregnant women and 100 HBV-exposed infants. 
3.3 
Study Population 
The study will not enroll participants who are severely sick and who require prolonged hospitalization.  
Pregnant women who establish care prior to 24 weeks’ gestation at Binza and Kingasani maternity centers will 
be eligible for enrollment. They must enroll prior to 24 weeks in order to have time to classify their disease 
status as high-risk and start antiviral prophylaxis between 28 and 32 weeks of gestation. Eligible women 
should intend to deliver their infants and follow up for post-partum visits only at Binza and Kingasani.  
Regarding infant enrollment criteria, all infants born to HBV-infected mothers will be eligible for the study. All 
should undergo HBV testing at birth and at 6 months of life. All HBV-exposed infants will receive the birth dose 
of HBV vaccine, regardless of birth weight 
(https://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm224503.pdf, 
Section 5.3). 
 
4 
STUDY PROCEDURES (what will be done) – Refer to Appendix B for an outline of these procedures. 
4.1 
Screening/Baseline Visit procedures 
Visit 1: Enrollment and baseline data collection 
1. HBsAg screening: All pregnant women presenting to the two selected MCH clinics for their first 
ANC visit will be eligible for enrollment in the study. Once verbal consent is obtained, the 
women will be screened for HBV with point-of-care HBsAg testing. Those who test positive for 
HBsAg will provide written consent to participate in the study. The counseling and testing will 
be integrated into the existing counseling and testing for HIV during the first ANC visit, and will 
be carried out by clinic nurses in charge of PMTCT. Women with new HBV diagnoses will have 
individual counseling regarding the study and to answer any questions they have prior to going 
through the consent process. 
2. Consent: Verbal consent will be obtained from all women by trained nursing personnel prior to 
testing for HBsAg. Women who test positive for HBsAg will then be consented using written 
consent forms. The eligibility screening document in Appendix D will be used to determine if an 
HBV-positive woman is eligible for interventions. If she is not eligible, the reason will be noted 
in Appendix C. If the woman is eligible, the consent form will be read to her to make sure she is 
willing to voluntarily participate in the study. If she refuses to consent to the study, the reasons 
for her refusal will be noted in Appendix C. If she would like to discuss the study with family 


 
13 
members prior to consenting, another meeting will be arranged. If she consents to participate, 
enrollment will proceed. 
3. Enrollment interview: Study personnel will ensure that there is sufficient space to guarantee 
confidentiality during the interview. They will then administer the questionnaire (Appendix J) 
and note responses. At the end of the interview, study personnel will verify that all questions 
have been completed, that the woman understands the process of the study and that she 
knows the date of her next visit. 
4. Maternal testing: A venous blood sample will be collected from the mother to test for the 
following: HBV viral load, HBeAg, platelets, BUN/Cr, ALT and AST. HIV status will also be 
determined. At the same time, a DBS sample will be obtained from the mother to test for HBV 
viral load and HBeAg. 
 
4.2 
Intervention/Treatment procedures (by visits) 
Visit 2: 2-4 weeks post-enrollment 
1. Results of laboratory testing: Study personnel will share the results of the HBV viral load 
and/or HBeAg testing with the participant. Baseline laboratory results (platelets, BUN/Cr, ALT, 
AST) will be reviewed by the study physician and any abnormalities will be communicated with 
the participant.  
2. Discussion of antiviral treatment initiation: HIV-negative mothers with positive HBeAg and/or 
high HBV viral load (>106) should be started on tenofovir +/- lamivudine between 28 and 32 
weeks of gestation. Women with significant baseline lab abnormalities (either GFR <50 and/or 
other significant abnormalities as determined by the study physician) will be excluded from 
receiving antiviral therapy.   
 
Visits 3 and 4: Subsequent pre-delivery visits 
There are no particular procedures at these visits. Study personnel will ensure, however, that any HIV-negative 
women who require antiviral treatment are started on therapy at the appropriate time (between 28 and 32 
weeks gestation). The Medication Documentation Form (Appendix G) will be used to monitor adherence using 
pill count during the monthly refill visit. Also, if any women have baseline laboratory abnormalities and require 
additional testing, they may undergo additional testing at these visits under the guidance of the study 
physician. 
Visit 5: Delivery/Birth 
1. Maternal testing: A venous blood sample will be collected from the mother to send for HBV 
viral load, BUN/Cr, ALT and AST. A DBS sample will be collected at the same time for HBV viral 
load testing. 
2. Infant testing: Research personnel will collect a blood sample (via heel stick) from the infant for 
HBsAg testing. 
3. Infant vaccination: The infant should receive the first dose of HBV vaccine within 24 hours of 
life. The date and time of administration of the vaccine will be documented in the Vaccine Log 
(Appendix H). 
 
4.3 
Follow- up procedures (by visits) 
Visit 6: 10 weeks post-partum 


 
14 
1. Maternal testing: A venous blood sample will be obtained from mothers who are receiving 
antiviral therapy for ALT and AST testing. 
2. Preparation for treatment cessation: 12 weeks marks the end of antiviral treatment for the 
woman. If her ALT is greater than 2x the upper limit of normal at the 10-week visit, she will 
require a referral to Dr. Mbendi, the gastroenterologist at KSPH. 
 
Visit 7: 6 months post-partum 
1. Maternal testing:  A venous blood and DBS sample will be collected from the mother for HBV 
viral load, AST and ALT testing. If the ALT level is greater than 2x the upper limit of normal, she 
should be referred to Dr. Mbendi. 
2. Infant testing: Serum and DBS samples will be collected from the infant for HBsAg and HBsAb 
testing. 
3. Exit Interview: The exit interview (Appendix K) will be administered to all HBV-positive 
mothers.  
 
4.4 
Unscheduled visits: All pregnant women will be seen at scheduled antenatal visits, and will be able to 
present for care as needed at other points in the antenatal period. Women will be encouraged to seek 
care if they experience any side effects from the medication. No additional interventions will be 
planned at these unscheduled visits. 
4.5 
Concomitant Medication documentation: Appendix I is the medication documentation form that will 
be filled out at each follow-up visit while the mother is taking tenofovir +/- lamivudine. 
4.6 
Subject Completion/ Withdrawal procedures: The exit survey will be administered to all HBV-positive 
mothers upon completion of the study (at 24 weeks postpartum). Women may be withdrawn from the 
study if they wish to withdraw from the study, if they experience a loss of their pregnancy or fetal 
demise, or if they fail to comply with study procedures. The reason for withdrawal will be clearly 
documented (Appendix F). 
4.7 
Screen failure procedures: Women who screen negative for HBV initially will not be enrolled in the 
intervention cohort. 
 
 
5 
STUDY EVALUATIONS AND MEASUREMENTS (how measurements will be made)   
5.1 
Feasibility Evaluation 
 For specific aim 1, we will determine the feasibility of the testing strategy by measuring acceptability to 
patients and staff, and ease of sample collection and transport. Feasibility will be measured qualitatively, as an 
aggregate of questionnaire responses from study participants and research staff. The final questionnaire is still 
in progress, but a draft of the questionnaire can be found in the appendix of the protocol document. 
Additionally, an implementation science component of this study will be added in the near future, to include 
focus groups comprised of research staff. The goal of this implementation science part of the study will be to 
determine factors that allow for feasibility and to extend the study to include areas outside of Kinshasa 
Province for future, larger studies. 


 
15 
We will also measure time from sample collection to return of results to mothers and additional cost of HBV 
testing to the PMTCT+ program.  
For specific aim 2, we will determine the feasibility of the interventions by evaluating patient and staff survey 
responses. We will also measure how many and when women and their infants are lost to the treatment 
cascade. 
5.2 
Laboratory Evaluation  
Secondary measures of specific aim 1 will include agreement between test characteristics (sensitivity, 
specificity, positive predictive value, negative predictive value) of HBeAg and HBV viral loads in DBS and 
venous blood samples.  
For specific aim 2, we will measure the following: percentage of women with highly active HBV who achieve 
reduction or suppression of HBV viremia, development of ALT elevation during or after antiviral treatment, 
resolution of e antigen positivity, and rate of MTCT of HBV (measured as the proportion of infants born to 
HBV-positive mothers who test positive for HBV). 
5.3 
Safety Evaluations 
At each follow-up visits, research staff will complete the medication documentation form, which will include 
information on pill counts as well as any reported side effects. The study physician will review these forms if 
side effects are reported. If a woman experiences severe side effects or severe intolerability, the medication 
will be discontinued. Infants will be monitored for at least 24 hours after receipt of the monovalent HBV 
vaccine, and any adverse reactions will be recorded. 
Safety monitoring will occur on an ongoing basis by the Kinshasa-based research team, by reporting adverse 
side effects and other concerns to the study physician. The UNC-based research team will evaluate these 
concerns on a monthly basis. While the likelihood of terminating the study early due to safety concerns is 
minimal, study personnel will consider this if there is a high frequency of safety concerns related to antiviral 
therapy and/or monovalent HBV vaccine. See Appendix B (Part 2) for an algorithm concerning monitoring of 
women on antiviral therapy. 
 
6 
STATISTICAL CONSIDERATION     
6.1 
Outcomes 
For specific aim 1, the feasibility of the testing strategy will be determined by responses to questionnaires for 
both study participants and staff. Dr. Rohit Ramaswamy will help to determine cutoff values for feasibility upon 
creation of final versions of the questionnaires. Additionally, agreement of test characteristics (sensitivity, 
specificity, positive predictive value and negative predictive value) between DBS and venous blood testing of 
HBeAg and HBV DNA will be assessed. The purpose of this analysis is to determine whether DBS is a reliable 
measure for HBeAg and HBV viral load testing. If this is true, it could be a more cost-effective manner of 
screening women for high-risk disease in low-resource settings. We will also determine the additional costs of 
HBV screening to the PMTCT+ program. HBeAg positivity will be defined as a titer of ≥1.000 according to the 
Architect system.19 Subjects with HBV DNA values above 2,000 IU/mL (the assay’s limit of detection) will be 
considered HBV-positive and those >200,000 IU/mL will be considered high-risk HBV. 


 
16 
For specific aim 2, we will measure how many and when women and their infants are lost to the treatment 
cascade; the percentage of women with highly active HBV who receive antiviral treatment and who achieve 
reduction or suppression of HBV viremia, the development of ALT elevation during or after treatment, and 
resolution of e antigen positivity; loss-to-follow-up (LTFU, percentage of women who are initiated on antiviral 
treatment but are not able to complete the recommended course) and adherence to antivirals and vaccination; 
and the rate of mother-to-child transmission (MTCT) of HBV, defined as the proportion of infants born to HBV-
positive mothers who test positive for HBV.  
Of note, no hypothesis testing will be performed for this study. Rates of MTCT of HBV in this study will be 
compared to historical controls. 
6.2 
Statistical Methods 
Specific Aim 1.  Frequencies of responses on surveys will be calculated and aggregate responses will be reported. 
We will determine agreement of test characteristics (sensitivity, specificity, negative predictive value and 
positive predictive value) of HBeAg and viral load using DBS compared to the gold standard of venous blood 
testing using Bland-Altman plots. 
Specific Aim 2. Percentages of women with highly active HBV will be compared with historical results obtained 
from the literature. Rates of infant HBV vaccination will be calculated. HBV MTCT will be determined by 
assessing infant HBsAg status at 6 months of age (the standard post-natal follow-up visit). These outcomes will 
be analyzed by proportional odds regression modeling. We will assess the percentage of women who initiate 
treatment during pregnancy who achieve suppression of HBV DNA (defined as HBV viral load <200,000 IU/mL). 
We will also assess the rate of development of immune-active hepatitis during or after the treatment period. 
LTFU and adherence rates will be compared between HIV-positive and HIV-negative groups, and time to drop 
out will be considered in our analysis. Cost analysis of interventions, including vaccination, antiviral treatment 
and healthcare provider time, will be performed. KAB survey results will be compiled and analyzed to determine 
the acceptability of this model of care. 
All population parameters will be accompanied by corresponding confidence intervals (CIs). Sensitivity analyses 
will also be performed to evaluate the study’s main results and to explore the influence of extreme or 
questionable data values. Statistical computations will be performed by Kristin Sullivan (PhD candidate in the 
department of epidemiology). Dr. Jonathan Parr will review all calculations. We expect very little missing data 
(i.e. Landis et al. Epid Infection, 2009). We will limit our final analyses to subjects with complete exposure and 
outcome data, with a table comparing demographics to assess for bias. 
6.3 
Sample Size and Power 
An estimated 5-9% of inhabitants of sub-Saharan Africa are infected with HBV.13-16 Based on these data and 
the preliminary rates of HBV positivity among pregnant women in the HIV PMTCT+ study and children in the 
DHS, we expected that of 2,000 women screened, about 5% (100 women) will have positive testing for HBsAg. 
However, in actuality, with a HBsAg prevalence of 2.8%, we will now screen 4,000 women in order to enroll 
100 HBsAg+ women. We will perform reflex HBeAg and HBV DNA testing in these patients who screen positive 
for HBsAg. Based on rates of HBeAg positivity reported in the literature,17,18 we expect that approximately 30-
50% (30-50) of these women will be classified as high-risk and will be treated accordingly. 
The sample size of 100 HBV-positive women has been chosen a priori due to limited funding for this pilot 
feasibility study. We expect to collect data in this study in order to apply for additional funding to conduct a 


 
17 
much larger study that will examine the influence of these testing and intervention strategies on the reduction 
of MTCT of HBV. 
6.4 
Interim Analysis: We do not expect to have to terminate the study early. However, we will be 
monitoring all women on tenofovir treatment for possible side effects and will perform appropriate 
quality control. 
 
7 
STUDY INTERVENTION (drug, device or other intervention details) 
7.1 
Tenofovir therapy: Tenofovir disoproxil fumarate will be obtained from Gilead, or combination 
lamivudine/tenofovir disoproxil fumarate will be obtained from PNLS. Per the package inserts (found at 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021356s042,022577s002lbl.pdf and 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022141s000lbl.pdf), tenofovir and 
combination lamivudine/tenofovir can be stored at room temperature. It will be packaged and labeled 
by pharmacy personnel at the designated maternity centers. Dosing of the antivirals will be 1 pill 
(300mg of each component or 300mg of TDF alone) once daily. We will monitor treatment compliance 
by use of a pill count when mothers present for monthly refills of the medication (to be documented in 
Appendix I). Treatment will be planned for ~6 months (starting at 28-32 weeks’ gestation and 
continuing through 24 weeks postpartum). Any returned drug will be destroyed according to existing 
policies within the maternity centers. The medication is not to be administered to anyone except for 
the designated pregnant female participants. 
7.2 
Monovalent HBV vaccine: Monovalent HBV vaccine (Euvax-B) will be obtained in the DRC. The vaccine 
will be stored refrigerated (between 2 and 8 degrees Celcius), according to FDA regulations. The dose 
will be 0.5mL for all HBV-exposed infants. The infant must receive the vaccine within 24 hours; date 
and time of administration will be recorded in Appendix J. Vials and needles will be disposed of in 
sharps containers after administration of the dose. 
 
8 
SAFETY MANAGEMENT 
The research team will monitor data for any safety concerns through routine quality assurance procedures 
that are already in place for the HIV PMTCT study. Mothers will be asked about any side effects while on 
tenofovir therapy at each monthly refill visit. As reported in the package inserts for tenofovir disoproxil 
fumarate and lamivudine + tenofovir disoproxil fumarate, the most common side effect of TDF alone is 
nausea (infrequent, 9%, mild severity), while common adverse reactions for the combination therapy include 
headache, pain, diarrhea and rash (>10%, mild severity). Severe reactions, including severe exacerbation of 
hepatitis, renal impairment, lactic acidosis, pancreatitis and bone effects, are rare. Women may develop 
immune-active hepatitis (ALT>2x the upper limit of normal) upon discontinuation of the medication. Per the 
study protocol, we will monitor pregnant women with ALT and creatinine at delivery, followed by ALT at 10 
and 24 weeks postpartum. The medication will be discontinued if any severe reactions are noted by clinical or 
study personnel. Any safety concerns surrounding antiviral treatment of pregnant women or vaccination of 
infants will be noted by the study nurses and reported to the appropriate study personnel (study physician 
and study coordinator) as soon as possible. These events will be reviewed by the rest of the research team. 
Safety monitoring will occur on an ongoing basis by the Kinshasa-based research team, by reporting any 
adverse events or other concerns to the study physician. The UNC-based research team will review these 
adverse events on a monthly basis. While the likelihood of terminating the study early due to safety concerns 


 
18 
is minimal, study personnel will consider this if there is a high frequency of safety concerns related to antiviral 
therapy. 
There is a possibility for an adverse reaction to the HBV vaccine, in which case study personnel will clearly 
document the reaction and the infant will be closely monitored. Infants delivered at the maternity health 
centers are not sent home with their mothers until day 2 or 3 of life, so there will be adequate time to observe 
the infants after vaccination. 
There are no known harms of tenofovir or lamivudine treatment of pregnant women on the developing fetus. 
There is no contraindication to breastfeeding while on tenofovir +/- lamivudine therapy.  
9 
DATA COLLECTION AND MANAGMENT  
Our study team will make every effort to maintain confidentiality of the data. This will occur mainly by the use 
of a unique maternity code for participants, rather than PHI. This code will be used on documents (including 
questionnaires) and to label patient specimens.  
Data will be collected by research personnel in the form of paper questionnaires and forms, and then will be 
entered into the electronic system. Each week, all completed data collection forms will be returned to the 
central office in Kinshasa, where the study site supervisors (Noro Lantoniaina, Bienvenu Kawende and Fathy 
Malongo) will check the forms for completeness and consistency. Incomplete forms will be returned to the 
interviewer for correction. Completed forms will be entered into the electronic database (Access or EpiData) 
and uploaded on the server through a secured FTP channel. The research team at UNC will upload data on a 
biweekly basis to run frequency distributions in order to identify unreasonable values, which will be returned 
to the research team in Kinshasa for correction. 
The paper documents that contain PHI will be stored in locked containers with the key stored separately. The 
electronic databases that contain PHI will be password-protected and only accessible to appropriate study 
personnel. Data that is shared with the rest of the research team will be done so in a de-identified manner 
when possible, using only maternity codes as identifiers. Data that is shared electronically will be done so only 
through secure, encrypted pathways. Public presentations and publications will not include any identifying 
information. 
 
10 
RECRUITMENT STRATEGY 
We will select study participants from the population of pregnant women presenting for care at two antenatal 
clinics in Kinshasa Province, DRC. Women who consent to participating in the study will be screened for HBV 
with HBsAg testing. Those who are negative will not be enrolled into the intervention cohort in the study. 
Women with positive testing will be enrolled, further blood specimens will be obtained, and the rest of the 
procedures of the study will be explained in depth to them at that time. 
Binza and Kingasani maternity centers combined see over 1,000 deliveries a month. With an estimated HBV 
prevalence of 5% among pregnant women (from the ongoing R01 study of PMTCT of HIV), we could 
theoretically screen 4,000 women and enroll all 100 HBV mono-infected pregnant women within the first 


 
19 
several months of the study. We have already screened 1,884 women in a 2-2.5 month period. Since our 
recruitment will occur over a one-year period, we should have no trouble recruiting these women.  
We hope to enroll a total of 100 infants, to whom we will administer the monovalent HBV vaccine at birth.  
We will maintain confidentiality of the individual study participants by interviewing them in a private room or 
area of the maternity center, away from other mothers or family members. Once the initial enrollment is 
complete, subjects will subsequently be identified using a maternity code. The same maternity code will be 
used for their infants.  The linkage code that contains PHI will be stored in a locked cabinet, with access limited 
to research personnel. 
11 
CONSENT PROCESS 
Research personnel in Kinshasa will obtain consent from study participants in their native language (French or 
Lingala). These personnel will be separate from those providing clinical care. We will train research personnel 
to emphasize in the consent process that participation in the study is completely voluntary and will not affect 
their prenatal care. The consent process will occur in a private area of the maternity center, separate from 
other patients and family members. Mothers could choose to delay enrollment to a subsequent prenatal visit, 
as long as they present for the first antenatal visit early enough in gestation (prior to 24 weeks) for this to be a 
feasible option.  
As part of the initial consent process, mothers will be consented provide permission to enroll their infants 
upon birth. Some mothers may be younger than 18, however they will be considered emancipated minors 
given their pregnant status, and will be able to sign the consent forms themselves as long as they are over the 
age of 15 years. 
 
12 
PLANS FOR PUBLICATION 
Upon completion of this study, we plan to present our findings at an international conference such as the 
Conference on Retroviruses and Opportunistic Infections (CROI). We will then publish findings in a journal such 
as Clinical Infectious Diseases. 
13 
REFERENCES  
1   Stanaway JD, Flaxman AD, Naghavi M, et al. The global burden of viral hepatitis from 1990 to 2013: findings 
from the global Burden of Disease Study 2013. Lancet 2016;388(10049):1081-1088. 
2   Mast EE, Margolis HS, Fiore AE, et al. Advisory Committee on Immunization Practices. A comprehensive 
immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: 
recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of 
infants, children and adolescents. MMWR Recomm Rep. 2005;54(RR-16):1-31. 
3   André FE, Zuckerman AJ. Review: protective efficacy of hepatitis B vaccines in neonates. J Med Virol. 
1994;44(2):144-151. 
4   World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic 
hepatitis B infection.              Published March 2015. Available at: 
http://apps.who.int/iris/bitstream/10665/154590/1/9789241549059_eng.pdf Accessed 9 May 2017. 


 
20 
5   World Health Organization. Democratic Republic of the Congo: WHO and UNICEF estimates of 
immunization coverage. Published 2015. Available at: 
http://www.who.int/immunization/monitoring_surveillance/data/cod.pdf Accessed 23 January, 2017. 
6   Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active 
immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012;19(2):e18-25.  
7   Song YM, Sung J, Yang S, Choe YH, Chang YS, Park WS. Factors associated with immunoprophylaxis failure 
against vertical transmission of hepatitis B virus. Eur J Pediatr 2007;166:813-818. 
8   Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. 
Pediatrics 2015;135(5):e1141-e1147. 
9   Pan CQ, Duan Z, Dai E, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. 
NEJM 2016;374(24):2324-2334.  
10 Brown RS, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during 
pregnancy: A systematic review and meta-analysis. Hepatology 2016;63(1):319-33.) 
11 Terrault NA, Bzowej NH, Chang K, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 
2016;63(1):261-283. 
12 Chen HL, Lee CN, Chang CH et al. Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-
to-infant transmission of hepatitis B virus. Hepatology 2015;62:375-86. 
13 Pirillo MF, Scarcella P, Andreotti M, et al. Hepatitis B virus mother-to-child transmission among HIV-
infected women receiving lamivudine-containing antiretroviral regimens during pregnancy and breastfeeding. 
J Viral Hepat 2015;22:289–96. 
14 Hoffmann CJ, Mashabela F, Cohn S, et al. Maternal hepatitis B and infant infection among pregnant 
women living with HIV in South Africa. J Int AIDS Soc 2014;17:18871. 
15 Seremba E, Ssempijja V, Kalibbala S, et al. Hepatitis B incidence and prevention with antiretroviral therapy 
among HIV positive individuals in Rakai, Uganda. AIDS 2017. doi: 1097/QAD.0000000000001399. [Epub ahead 
of print]. 
16 Lemoine M, Shimakawa Y, Njie R, et al. Acceptability and feasibility of a screen-and-treat programme for 
hepatitis B virus infection in The Gambia: the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) 
study. Lancet Glob Health 2016;4:e559–e567. 
17 Andersson MI, Maponga TG, Ijaz S, et al. The epidemiology of hepatitis B virus infection in HIV-infected and 
HIV-uninfected pregnant women in the Western Cape, South Africa. Vaccine 2013;31(47):5579-5584. 
18 Wen WH, Chang MH, Zhao LL et al. Mother-to-infant transmission of hepatitis B virus infection: Significance 
of maternal viral load and strategies for intervention. Journal of Hepatology 2013;59:24-30. 
19 Architect System: HBeAg, Package Insert. Abbott Laboratories 2008. Available at: 
http://www.ilexmedical.com/files/PDF/HBeAg_ARC.pdf Accessed 26 January 2017. 
20 World Health Organization. Guideline on when to start antiretroviral therapy and pre-exposure prophylaxis 
for HIV. Published Sept 2015. Available at: 
http://apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf?ua=1 Accessed 26 April 2017. 


 
21 
21 The International Organization for Standardization. ISO 5725-1 Accuracy (trueness and precision) of 
measurement methods and results. 1994. Available at: https://www.iso.org/obp/ui/#iso:std:iso:5725:-1:ed-
1:v1:en Accessed 27 April 2017. 
 
 
15      APPENDICES 
Appendix A: Logic Model 
 
 
 
 
 
 
 
 
 
 


 
22 
 
 
 
 
 
Appendix B:  
Part 1: General Study Screening and Management Algorithm 
 
 
 
 
 


 
23 
 
 
 
 
 
Part 2: Management of HIV-negative Women with High-risk HBV on Antiviral Therapy 
 
 
 
 
 
 
 
 
 
 
 
 


 
24 
Appendix C: Screening and Enrollment Sheet  
Instructions:  Use this table to record all women contacted who were (a) ineligible to participate in the study, 
(b) refused to participate after hearing about the study, (c) who were not interested in hearing about the study 
or (d) who were eligible and enrolled into the stud. Do not record the name of the woman. If the woman was 
ineligible or refused to participate, please record reason for ineligibility or for refusal.  If she was eligible and 
enrolled into the study, record her participant ID number 
Number Date 
Is the woman   
1-ineligible  OR did the 
woman  
2-refuse OR was the 
woman  
3-not interested  in 
hearing about the 
study OR was she 
 4-Eligible?   
Write below the 
number of the answer 
Reason for 
ineligibility 
(enter the 
code*) 
 
Reason for refusal 
Write below the number of 
reason the woman refused 
to participate 
1– don’t want to 
participate 
2 – don’t have husband’s 
permission 
3 – don’t have time 
4 – others (specify) 
 
For women 
ELIGIBLE: 
Write below the 
Participant ID 
number 
0001 
 
 
 
 
 
0002 
 
 
 
 
 
0003 
 
 
 
 
 
0004 
 
 
 
 
 
0005 
 
 
 
 
 
0006 
 
 
 
 
 
0007 
 
 
 
 
 
0008 
 
 
 
 
 
0009 
 
 
 
 
 
0010 
 
 
 
 
 
*1 – Presented after 24 weeks’ gestation 
2- Does not intend to stay in Kinshasa until delivery and 6 weeks post-partum 
3-  Is severely ill and require hospitalization 
 


 
25 
 
 
Appendix D: Eligibility Checklist for Participants 
ELIGIBILITY CHECKLIST FOR PARTICIPANTS 
YES 
NO 
1. The gestational age  is  ≤24 weeks completed  
□ 
□ 
2. The participant intends to stay in Kinshasa through delivery and six 
weeks postpartum 
□ 
□ 
3. The participant is NOT severely sick and does NOT require extended 
hospitalization 
□ 
□ 
IF THE ANSWER OF ONE OF THESE QUESTIONS IS NO, THE PARTICIPANT IS NOT ELIGIBLE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix E: Master Appointment Sheet for Interviewers 
 
 
 


 
26 
 
 
 
 
 
 
 
 
Participant 
ID# 
Current visit 
date 
Next follow-up visit 
date 
Observation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Site number ____________ 
 


 
27 
Appendix F: Master Withdrawal or Termination Sheet 
Instructions:  Use this table to record all participants who refuse to continue their participation in the study. Do 
not record the name of the woman. Please record reason for withdrawal.   
Participant 
ID# 
Date 
Visit 
Reason for withdrawal 
Write below the number of reason the mother is ineligible: 
1– No reason                                            2 – Husband’s request 
3 – Don’t have time                                3 – Loss of pregnancy  
4 – Baby died                                           5 – others (specify) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
28 
 
Appendix G: Medication Documentation Form 
Instructions:  Use this table to record all information pertaining to medication administration.  
 
Participant 
ID# 
Date 
of 
Visit 
Pill 
Count 
(# out of 
30) 
Side Effects 
Reported (if 
any) 
Date 
Antiviral  
Course  
Initiated 
Date 
Antiviral 
Course 
Completed 
Reason for 
Premature 
Termination 
(if any) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
29 
Appendix H: Vaccine Log 
 
Instructions:  Use this table to record information about infant vaccination. Timing is very important – all 
infants should receive the vaccine within 24 hours of life!  
 
Participant 
ID# 
Date 
of Birth 
Time of 
Birth 
Birth 
Weight 
(kg) 
Date of 
Vaccination 
Time of 
Vaccination 
Adverse Reaction (if 
any) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix I: Dried-Blood Spot (DBS) Collection and Handling 


 
30 
 This SOP describes the procedures of collecting and handling whole blood on filter paper (DBS) for storage 
I. Material storage 
The  Kit can be stored at room temperature ( 22 - 25 °C )  
II.Required supplies for DBS 
1) Permanent marker (pointe fine)Filter paper collection devices 
2) Gloves without talcum 
3) Sterile lancetsAlcohol 70°Cotton wool 
4) Sealable plastic bags 
5) Humidity cards 
6) Dessicant packs 
7) Glycine  weighing paper  
8) Eau de javel (concentration   
9) Sample rack for drying process  
10) Sharp container 
 
Steps prior to sample collection 
 Well lighted room 
 
III. DBS sample collection 
Use universal safety precautions while handling biological fluids and tissues 
  Clearly label the card with the participant ID number   
  Do not touch circles 
 
The sample collection is an essential part of the testing : 
 
1) Wear gloves 
2) Position the patient. 
3) Cleanse the 3rd or 4th finger (or heel) with alcohol and wait for 30 second to allow it to dry. 
4) Puncture finger or heel with sterile, disposable lancet. Do not “milk” blood from the finger. 
5) Wipe away first drop of blood with dry cotton wool 
6) When next large drop of blood appears, touch filter paper circle to blood. Do not touch paper to skin 
7) Completely fill the circle with the blood Fill at least three circles with blood drops for adults and at least 
two circles with blood for children. 
Dry the DBS sample using the sample rack with slots where the filter paper specimen should be inserted  
 
IV. Drying DBS 


 
31 
• 
Avoid touching or smearing the blood spots 
• 
Allow the specimen to fully air dry horizontally at least 3hours or all night  at room temperature 
• 
Keep away from direct sunlight , dust and insects 
• 
Do not heat, stack or allow DBS to touch other surfaces during the drying process 
Allow the DBS sample to completely dry before packaging. 
 
V. Package of DBS for storage 
At the end of each day, package the dried samples (wait until next day if some samples are not dried yet after 
3 hours)Store the samples and ship them every week (Contact the lab coordinator  to organize the shipping 
process) Place each  filter paper between sheets of weighing paper to prevent cross contamination. 
 
1) Insert the dried filter papers in plastic bags : one plastic bag may contain up to 10 samples.  
2) Add 2 to  4 dessicant packet 
3) Add humidity cards 
4) Seal the plastic bag after driving out residual air . 
 
5) Label the bag 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
32 
Appendix J: Participant Enrollment Interview  
When to give the interview: At the first encounter during pregnancy  
Objective of the interview:  To collect demographic, economic, and psychosocial information and measure 
perception of PMTCT risk 
 
A. GENERAL INFORMATION (PLEASE PRINT CLEARLY) 
A1. Facility Name: 
____________________________________________________________________________________  
A2. Last name:   
 
 
 
 
 
 
 
A3. First name:   
 
 
 
 
 
 
 
A4. Address: _________________________________________________________________________ 
Use the following space to note the major landmarks for this address: ____________________________ 
____________________________________________________________________________________ 
____________________________________________________________________________________  
A5. Telephone Number: ___________________________________ 
A6. Who can we contact in case we are unable to reach you directly?  
Last and First Name of the contact: ___________________________________ 
Telephone Number of the contact: ______________________________________ 
 
 
 
 
 
 
 
(REMOVE THIS PAGE BEFORE SENDING FOR DATA ENTRY) 
 
 


 
33 
B. Confirmation of HIV and Hepatitis B status  
 
C. Obstetrical history  
1 
Date of Last Menstrual Period 
__/__/____DD/MM/YYYY  
 Don’t Know 
2 
Gestational age in weeks 
IF LMP UNKNOWN USE THE CLINICAL ESTIMATION 
FROM ANC REGISTER 
 
____weeks 
3 
Including this pregnancy, how many times have you 
been pregnant (even if the pregnancy did not result in 
the birth of a live child)? 
 
_______________ 
 FIRST PREGNANCY          (1)  
 
 
6 
4 
When was the last delivery? 
 1 YEAR OR LESS    (1) 
 2 YEARS                (2) 
 3 YEARS                (3) 
 4 YEARS                (4) 
 5 YEARS OR MORE (5) 
5 
How many children are still alive? 
_________ 
a 
How old is/are he/she/they? 
1st _______ 
2nd _______ 
3rd _______ 
4th _______ 
5th _______ 
6th _______ 
7th _______ 
8th _______ 
9th _______ 
10th ______ 
6 
Do you have an antenatal care card/book 
with you today? 
IF YES: ASK TO SEE THE CARD/BOOK. 
 Yes                             (1)                                
 No, CARD KEPT WITH FACILIT(2)    SKIP TO D 
 NO CARD/BOOK USED  (3)             SKIP TO D 
         
a 
How many weeks pregnant is the client, according to the ANC 
card? 
# of weeks _______ 
NOT AVAILABLE       (99) 
b 
Has the mother received hepatitis B vaccine according to the 
book? If so, please note the # of doses. 
 YES, ______ doses       (1)               
 NO                              (2) 
 UNKNOWN                   (8) 
 
D. Disclosure of Hepatitis B status 
1 
HAS THE PARTICIPANT HAD A POSITIVE 
HEPATITIS B TEST? 
 YES           (1) 
 NO            (2)       STOP THE INTERVIEW 
2 
Has the participant ever been told that she has 
hepatitis B in the past (before today)? 
 YES           (1) 
 NO            (2) 
3 
HAS THE PARTICIPANT HAD A POSITIVE HIV 
TEST? 
 YES           (1) 
 NO            (2)  


 
34 
 
E. Patient satisfaction with care received  
1 
Have you told anyone that you have Hepatitis B? 
 No   (2) 
 Yes  (1) 
2 
a 
Who did you disclose to? 
 PARTNER/FATHER OF MY BABY  (1) 
 MY MOTHER                             (2) 
 MY SISTER                               (3) 
 OTHER __________________   (6) 
                  (SPECIFY) 
2 
Do you know the Hepatitis B status of your 
partner? 
 NO     (2) 
 YES    (1) 
3 
a 
What is his status  
 POSITIVE   (1) 
 NEGATIVE  (2) 
3 
During this visit (or previous visits) has a provider 
discussed with you about inviting your partner to 
come to the clinic with you? 
 YES, THIS VISIT ONLY              (1) 
 YES, THIS & PREVIOUS VISIT    (2) 
 YES, PREVIOUS VISIT ONLY      (3) 
 NO                                          (4)  
 DON’T KNOW                           (8)  
4 
Have you ever received a hepatitis B vaccine? If 
so, how many doses? 
 YES, ______ doses                   (1)                             
 NO                                          (2) 
 DON’T KNOW                           (8) 
Now I am going to ask you some questions about the services you received today. I would like to have your 
honest opinion about the things that we will talk about. This information will help improve services in 
general. 
1 
How long did you wait between the time you arrived at 
this facility and the time you were able to see a 
provider for the consultation? 
___H___MINUTES  SAW PROVIDER
 
IMMEDIATELY….0000 
 DON'T KNOW…..9898 
 
2 
Now I am going to ask about some common problems clients have at health facilities. As I mention 
each one, please tell me whether any of these were problems for you today, and if so, whether they 
were major or minor problems for you. 
 
 
MAJOR   MINOR   NO PROBLEM   DK 
a 
Time you waited to see a provider 
 (1)      
 (2)      
 (3)      
(8) 
b 
Ability to discuss problems or concerns about your 
pregnancy 
 (1)      
 (2)      
 (3)      
(8) 
c 
Amount of explanation you received about the 
problem or treatment 
 (1)      
 (2)      
 (3)      
(8) 
d 
Privacy from having others see the examination 
 (1)      
 (2)      
 (3)      
(8) 
e 
Privacy from having others hear your consultation 
discussion 
 (1)      
 (2)      
 (3)      
(8) 
f 
Availability of medicines at this facility 
 (1)      
 (2)      
 (3)      
(8) 
g 
The hours of service at this facility, i.e., when they 
open and close 
 (1)      
 (2)      
 (3)      
(8) 
h 
The number of days services are available to you 
 (1)      
 (2)      
 (3)      
(8) 


 
35 
 
F. Travel Distance 
i 
The cleanliness of the facility 
 (1)      
 (2)      
 (3)      
(8) 
j 
How the staff treated you 
 (1)      
 (2)      
 (3)      
(8) 
k 
Cost for services or treatments 
 (1)      
 (2)      
 (3)      
(8) 
3 
Are you a part of any prepayment plan (such as worker 
insurance or a similar program) or institutional 
arrangement that pays for some or all of the services 
you receive at this or any other facility? 
 YES                         (1) 
 NO                          (2) 
 DON’T KNOW           (8) 
4 
Were you charged, or did you pay fees for any 
services you received or were provided today? 
 YES     (1) 
 NO     (2)               GO TO 5 
a 
What is the total amount you paid for all services or 
treatments you received at this facility today? 
Total amount____________ FC 
 DON’T KNOW           (98) 
5 
Is this the closest health facility to your home? 
 YES                         (1) 
 NO                          (2) 
 DON’T KNOW           (8) 
6 
a 
What was the main reason you did not go to the 
facility nearest to your home?  
IF CLIENT MENTIONS SEVERAL REASONS, PROBE 
FOR THE MOST IMPORTANT, OR MAIN REASON. 
CHECK ONLY ONE RESPONSE 
 INCONVENIENT OPERATING HOURS  (01) 
 BAD REPUTATION                            (02) 
 DON’T LIKE PERSONNEL                   (03) 
 NO MEDICINE                                  (04) 
 PREFERS TO REMAIN ANONYMOUS    (05) 
 IT IS MORE EXPENSIVE                    (06) 
 WAS REFERRED                               (07) 
 OTHER_______________________  (96) 
 DON’T KNOW                                  (98) 
6 
In general, which of the following statements best describes your opinion of the services you either 
received or were provided at this facility today 
READ ALL STATEMENTS, CHECK ONLY ONE 
a) I AM VERY SATISFIED WITH THE SERVICES I RECEIVED IN FACILITY          
  (1) 
b) I AM MORE OR LESS SATISFIED WITH THE SERVICES I RECEIVED             
  (2) 
c) I AM NOT SATISFIED WITH THE SERVICED I RECEIVED                              
  (3) 
7 
Will you recommend this health facility to a friend or 
family member? 
 YES                         (1) 
 NO                          (2) 
 DON’T KNOW           (8) 
Read: Now I am going to ask you a couple of questions about transportation. 
1 
How long does it take for you to come to this maternity 
(one-way) 
_____ min 
2 
How will you usually come to the maternity? 
 Walk             (1) 
 Taxi              (2) 
 Other________ (3) 
 
    G 
 
 
 


 
36 
 
G. Perception of Hepatitis B and MTCT Risk 
Read: Now I am going to ask you some questions about your understanding of Hepatitis B and the risk of 
passing it on to your baby during pregnancy or childbirth. 
1. In your opinion, how serious a disease is hepatitis 
B?   
 Very serious                    (1) 
 Somewhat serious            (2) 
 Not very serious,              (3) 
 Not at all serious?             (4) 
 Don’t Know                      (8) 
 Refuse to answer             (9) 
2. What are the signs and symptoms of hepatitis 
B (check all that apply)? 
 No symptoms                     (1) 
 Jaundice (yellowing of skin) (2) 
 Abdominal pain                   (3) 
 Rash                                  (4) 
 Don’t Know                         (8) 
 Refuse to answer               (9) 
3. How can a person get hepatitis B (check all that 
apply)? 
 Through handshakes            (1) 
 Through contact with blood from an infected 
person                                                 (2) 
 Through sharing dishes         (3) 
 Mother-to-child transmission  (4) 
 Sexual transmission              (5) 
 Through breastfeeding           (6) 
 Don’t Know                          (8) 
 Refuse to answer                  (9) 
4. How can mother-to-child transmission of 
hepatitis B be prevented (check all that apply)? 
 Infant vaccination at birth                  (1) 
 Antiviral treatment during pregnancy   (2) 
 Don’t Know                                       (8) 
 Refuse to answer                               (9) 
5. How difficult or easy will it be for you to come to 
the clinic for follow-up appointments for hepatitis B? 
Would it be: 
 Very difficult                    (1) 
 Somewhat difficult           (2) 
 Somewhat easy               (3) 
 Very easy?                      (4) 
 Don’t Know                     (8) 
 Refuse to answer             (9) 
6. What makes it difficult for you to come to the 
clinic to receive your treatment? (check all that 
apply) 
 Transportation                          (A) 
 No Childcare                             (B) 
 Takes too much time                 (C) 
 Husband/partner won’t allow      (D) 
 Other_________                        
H. Demographic characteristics 
a 
If taxi or paid transportation, what is the cost for one-way 
travel? 
_______FC 


 
37 
Now I am going to ask you some questions about yourself. I would like to have your honest responses as 
this information will help to improve services in general. 
1 
How old were you at your last birthday? 
PROBE TO DETERMINE THE AGE IF THE PARTICIPANT DOES 
NOT KNOW HER AGE 
AGE IN YEARS      __/__/ 
2 
In what day, month, and year were you born? PROBE TO 
DETERMINE AT LEAST THE YEAR 
__/__/____ 
 
3 
Are you currently married, separated, divorced, widowed or 
never married?  
 MARRIED (1)  
 SEPARATED (2) 
 DIVORCED (3) 
 WIDOWED  (4) 
 NEVER MARRIED (5) 
4 
a 
Are you currently living with someone in a marriage-like 
relationship? 
 Yes  (1) 
 No   (2) 
4 
Have you ever attended school? 
 Yes  (1) 
 No   (2)         SKIP TO I 
a 
What is the highest level of school you attended: primary, 
secondary, or higher? 
 Primary (1) 
 Secondary      (2) 
 Higher education  (3) 
b 
What is the highest (grade/form/year) you completed at that 
level? 
HIGHEST GRADE  __/__/ 
IF <1YEAR, ENTER “00” 
 
I. Mother’s Socio-economic Information 
Now I am going to ask you questions regarding your home, where you have been living since you learned 
that you were pregnant with this baby. If you have not been living consistently in a single home, think 
about where you will be living most of the time during this pregnancy. 
1 
How long have you lived at your current address? 
________Years ______ months 
DON’T KNOW = “98” REFUSED = “99 
2 
How many adults (people 18 and older) are living with you 
at home? 
_________ 
3 
How many children under 18 are living with you at home? 
_________ 
4 
How many rooms do you have in your house? 
_________ 
5 
Do you have electricity at your house? 
 Yes (1) 
 No  (2) 
6 
How many of the following, if any, do you have at your 
house:  
(ENTER "00" IF THE PATIENT DOES NOT HAVE THE ITEM OR 
IF THE ITEM IN QUESTION IS NOT WORKING) 
Beds _____________ 
Radios____________ 
TVs_______________ 
Mobile phones______ 


 
38 
Refrigerators_______ 
Bicycles___________ 
Motorcycles________ 
Car ______________ 
7 
With what do you cook at home? (check all that apply) 
 Wood/Charcoal (1) 
 Gas  (2) 
 Electric Stove (3) 
8 
What kind of water do you drink? (Check only one) 
 Private piped water    (1) 
 Piped water from the Neighbors 
(2) 
 Communal tap  (3) 
 Protected well   (4) 
 Spring/source water  (5) 
 Other (specify)_____________ (6) 
9 
Aside from your own housework, have you done any work in 
the last seven days? 
 Yes  (1)        [SKIP TO 13] 
 No   (2) 
10 
As you know, some women take up jobs for which they are 
paid in cash or kind. Others sell things, have a small business 
or work on the family farm or in the family business. 
In the last seven days, have you done any of these things or 
any other work? 
 Yes   (1)       [SKIP TO 13] 
 No    (2) 
11 
Although you did not work in the last seven days, do you 
have any job or business from which you were absent for 
leave, illness, vacation, maternity leave, or any other such 
reason? 
 Yes   (1)      [SKIP TO 13] 
 No    (2) 
12 
Have you done any work in the last 12 months? 
 Yes   (1) 
 No   (2)  [ SKIP TO THE END ] 
13 
What is your occupation, that is, what kind of work do you 
mainly do?  
 Market or street trader  (1) 
 Seamstress    (2) 
 Hairdresser    (3) 
 salaried      (4) 
 Other ________________  (6) 
14 
Do you do this work for a member of your family, for 
someone else, or are you self-employed? 
 Family member    (1) 
 Someone else      (2) 
 Self-employed      (3) 
 Government         (4) 
Check the questionnaire to make sure all question were asked and answers recorded appropriately. Thank 
the participant for taking her time to answer to your question and make sure she has received her 
compensation before letting her go.  
Date______/_______/_____________ 
 


 
39 
Initials of person completing form_______________ 
 
Appendix K: Participant Exit Interview 
When to give the interview: Six months post-partum or six months after the end of pregnancy 
Objective of the interview:  To collect information on satisfaction with care received. 
 
J. GENERAL INFORMATION (PLEASE PRINT CLEARLY) 
A1. Facility Name: 
____________________________________________________________________________________  
A2. Last name:   
 
 
 
 
 
 
 
A3. First name:   
 
 
 
 
 
 
 
A4. Address: _________________________________________________________________________ 
Use the following space to note the major landmarks for this address: ____________________________ 
____________________________________________________________________________________ 
____________________________________________________________________________________  
A5. Telephone Number: ___________________________________ 
A6. Who can we contact in case we are unable to reach you directly?  
 Last and First Name of the contact: ___________________________________ 
Telephone Number of the contact: ______________________________________ 
PREGNANCY OUTCOME: 
 SINGLE BIRTH 
 TWIN 
 STILLBIRTH 
 MISCARIAGE/ABORTION 
Infant PID #___________________; Status: 
 ALIVE 
 DEAD, DATE OF DEATH __/__/____ 
Twin 1 PID# ______________; 
Status: 
 ALIVE 
 DEAD 
DATE OF DEATH __/__/____ 
Twin 2 PID# ______________; 
Status: 
 ALIVE 
 DEAD 
DATE OF DEATH __/__/____ 
 
 
 
 
(REMOVE THIS PAGE BEFORE SENDING FOR DATA ENTRY) 
 
 


 
40 
K. Infant Status  
 
L. Mother’s status and Disclosure of HBV Status 
 
CLINICAL PARAMETERS 
 
1 
CHECK THE VACCINATION CARD OR THE APPROPRIATE REGISTER TO COLLECT THE FOLLOWING 
INFORMATION 
 
a 
WEIGHT 
___.__ __ __ KG;       NOT RECORDED 
 (99999) 
 
b 
LENGTH  
__ __ __ CENTIMERS; NOT RECORDED 
 (999) 
 
c 
HEAD CIRCUMFERENCE  
__ __ __ CENTIMERS; NOT RECORDED 
 (999) 
 
d 
HBsAg RESULTS  
 POSITIVE    (1) 
 NEGATIVE   (2) 
 NOT AVAILABLE (8) 
 
2 
VACCINATION  
 BCG ;        DATE __/__/__  DD/MM/YY 
 POLIO O;   DATE __/__/__  DD/MM/YY 
 POLIO I  ; DATE __/__/___ DD/MM/YY 
 POLIO II ; DATE __/__/___ DD/MM/YY 
 POLIO III; DATE __/__/___ DD/MM/YY 
 DPT  HepB Hib I    ;    DATE __/__/___ DD/MM/YY 
 DPT  HepB Hib II    ;    DATE __/__/___ DD/MM/YY 
 DPT  HepB Hib III   ;    DATE __/__/___ DD/MM/YY 
 PCV I   ;  DATE __/__/__ DD/MM/YY 
 PCV II   ; DATE __/__/__ DD/MM/YY 
 PCV III  ; DATE __/__/__ DD/MM/YY 
 VPI;   DATE __/__/__ DD/MM/YY 
 
1 
CHECK THAT THE CAREGIVER IS THE RECORDED 
PARTICIPANT (MOTHER) IN THE STUDY 
 YES,                                     (1) 
 NO, NOT THE BILOGICAL  
         MOTHER OF THE CHILD      (2)      
2 
a 
Where is the biological mother who was enrolled 
in the study? 
 DEAD  (1)   DATE __/__/__ DD/MM/YY 
 SICK, IN HOSPITAL (2) 
 SICK, AT HOME       (3) 
 OTHER (6)  
  SPECIFY ____________________ 
 
b 
What is your relation with the baby 
 GRAND MOTHER  (1) 
 AUNT (2)  
 SISTER (3)                                
 OTHER __________________ (6) 
  
 
DISCLOSURE OF HBV STATUS AND PARTNER INVOLVEMENT 
 
2 
Have you told anyone you have HBV? 
 No   (2) 
 Yes  (1) 
3 
a 
Who did you disclose to 
 PARTNER/FATHER OF MY BABY  (1) 
 MY MOTHER                             (2) 
 MY SISTER                               (3) 
 OTHER __________________   (6) 
 


 
41 
 
M. Visit and Medication Adherence  
When taking your daily Hepatitis B medications, it is normal that you might forget to take your medications, 
or not do so as directed by your nurse/doctor, and you may have your own reasons for taking your medication 
like you did. Please answer the following questions honestly so that the hospital staff will be able to help you 
ensure that you or other patients take their medications correctly in the future. 
                  (SPECIFY) 
3 
Do you know the HBV status of your partner 
 YES    (1) 
 NO     (2) 
 NOT TOGETHER ANY MORE (8) 
 
 
 
a 
What is his status  
 POSITIVE   (1) 
 NEGATIVE  (2) 
 
 
1 
Since being diagnosed with Hepatitis B, have you missed 
or were you late for a scheduled visit? 
 
 No 
Go to 
#4 
 Yes 
 
2 
How many visits did you miss? 
 1 
 
 2 
 
 3 or more 
 
3 
People may miss clinic visits for various reasons. Here is a list of possible reasons why you 
may have missed a visit. Think about the visit you missed, did you miss the visits because 
…(Check all applicable responses) 
 you did not have money for consultation fees 
 you did not have money for transportation 
 the distance is too far 
 your partner/husband prevented you 
 you didn’t want people to know about your HBV status 
 you didn’t understand why you needed to go to the visit 
 you didn’t take your pills 
 you had other commitments 
 you didn’t feel good/ you were in poor health 
 Other (specify): 
___________________________________________________ 
4 
Were you instructed to take antiviral medication during pregnancy? 
 Yes 
 No 
 Not sure 
5 
How often during pregnancy did you take your Hepatitis B medication in the dose and 
scheduling that your doctor told you to?  
(CHECK ONE) 
 None of the time  
 A little of the time 
 Some of the time   
 A good bit of the time 


 
42 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N. Patient satisfaction with care received  
1 
How long did you wait between the time you arrived 
at this facility and the time you were able to see a 
provider for the consultation? 
____ hours  /   ____ minutes 
SAW PROVIDER IMMEDIATELY(00/00) 
DON'T KNOW         (98/98) 
 
 Most of the time 
 All of the time 
 Did not take any medication 
6 
How often after delivery did you take your Hepatitis B-related medications in the dose 
and scheduling that your doctor told you to?  
(CHECK ONE) 
 None of the time  
 A little of the time 
 Some of the time   
 A good bit of the time 
 Most of the time 
 All of the time 
 Did not take any medication 
7 
Did you take any other medications during pregnancy? If so, please list the medications 
below.  
_________________________________________________________________________
_______________________________________________________________ 
 
Now I am going to ask you some questions about the services you or your baby received today. I would like 
to have your honest opinion about the things that we will talk about. This information will help improve 
services in general. 
2 
Now I am going to ask about some common problems clients have at health facilities. As I mention 
each one, please tell me whether any of these has been a problem starting when you arrived in this 
facility for the delivery, and if so, whether they were major or minor problems for you. 
 
 
MAJOR   MINOR   NO PROBLEM   DK 
a 
Time you waited to see a provider 
 (1)      
 (2)      
 (3)      
(8) 
b 
Ability to discuss problems or concerns about your 
child’s health 
 (1)      
 (2)      
 (3)      
(8) 
c 
Ability to discuss problems or concerns about your own 
health [IF RESPONDENT IS ENROLLED] 
 (1)      
 (2)      
 (3)      
(8) 
d 
Amount of explanation you received about the problem 
or treatment 
 (1)      
 (2)      
 (3)      
(8) 
e 
Privacy from having others see the examination 
 (1)      
 (2)      
 (3)      
(8) 
f 
Privacy from having others hear your consultation 
discussion 
 (1)      
 (2)      
 (3)      
(8) 
g 
Availability of medicines at this facility 
 (1)      
 (2)      
 (3)      
(8) 
h 
The hours of service at this facility, i.e., when they open 
and close 
 (1)      
 (2)      
 (3)      
(8) 
i 
The number of days services are available to you 
 (1)      
 (2)      
 (3)      
(8) 
j 
The cleanliness of the facility 
 (1)      
 (2)      
 (3)      
(8) 


 
43 
 
O. Acceptability of study 
Now I am going to ask you some questions about your feeling or what you think of the study that you 
participated in. I would like to have your honest opinion about the things we will discuss. 
1 
How was your experience of having your (the mother’s) blood drawn?  
(CHECK ONE) 
 Very unacceptable  
 Somewhat unacceptable 
 No opinion 
 Somewhat acceptable 
 Very acceptable 
 Did not allow study personnel to take my blood 
2 
How was your experience with having your infant’s blood drawn? (CHECK ONE) 
 Very unacceptable  
 Somewhat unacceptable 
 No opinion 
 Somewhat acceptable 
 Very acceptable 
 Did not allow study personnel to take my child’s blood 
3 
How was the experience of having your infant vaccinated at birth?   
(CHECK ONE) 
 Very unacceptable  
 Somewhat unacceptable 
k 
How the staff treated you 
 (1)      
 (2)      
 (3)      
(8) 
l 
Cost for services or treatments 
 (1)      
 (2)      
 (3)      
(8) 
3 
Is this the closest delivery facility to your home? 
 YES                         (1) 
 NO                          (2) 
 DON’T KNOW           (8) 
 
a 
What is the main reason you 
did not go to the facility 
nearest to your home?  
IF CLIENT MENTIONS 
SEVERAL REASONS, PROBE 
FOR THE MOST IMPORTANT, 
OR MAIN REASON. 
 INCONVENIENT OPERATING HOURS                                (1) 
 SEEKING BETTER QUALITY SERVICES                             (2) 
  NOT LIKE THE WAY IN WHICH I WAS TREATED IN OTHER FACILITY        
(3) 
  THIS FACILITY IS CLOSE TO MY HOUSE                          (4) 
  THIS FACILITY IS LESS EXPENSIVE                                (5) 
 WAS REFERRED                                                             (6) 
 OTHER________________________________________  (7) 
 
4 
In general, which of the following statements best describes your opinion of the services you 
received at this facility since arriving here for delivery 
READ ALL STATEMENTS, CIRCLE ONLY ONE 
d) I AM VERY SATISFIED WITH THE SERVICES I RECEIVED IN FACILITY              (1) 
e) I AM MORE OR LESS SATISFIED WITH THE SERVICES I RECEIVED                  (2) 
f) I AM NOT SATISFIED WITH THE SERVICED I RECEIVED                                  (3) 
 
5 
Will you recommend this health facility to a friend or 
family member? 
 YES                         (1) 
 NO                          (2) 
 DON’T KNOW           (8) 
 


 
44 
 No opinion 
 Somewhat acceptable 
 Very acceptable 
 Did not allow study personnel to vaccinate my infant 
4 
What is your opinion about taking a drug (tenofovir +/- lamivudine) during and after pregnancy to 
prevent transmission of the virus to the baby?   
(CHECK ONE) 
 Very unacceptable  
 Somewhat unacceptable 
 No opinion 
 Somewhat acceptable 
 Very acceptable 
 Did not allow study personnel to vaccinate my infant 
 
 
Check the questionnaire to make sure all question were asked and answers recorded appropriately. Thank 
the participant for taking her time to answer to your question and make sure she has received her 
compensation before letting her go.  
 
Date______/_______/_____________ 
 
Initials of person completing form_______________