Hep Mec Cohort in Zambia
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity of Alabama at Birmingham
About this trial
Observational cohort of adults with acute and chronic hepatitis B infection in Zambia, with and without HIV coinfection. Participants join the study at the time of diagnosis and before or at the time when they are starting antiviral treatments and then they are followed up over multiple years to assess changes to their liver and evolution of HBV (and HIV if applicable) infection. All treatments for HBV and HIV are standard per local Ministry of Health guidelines.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Group 1 (rx-naive chronic hbv mono): 18+ years old, HBsAg-positive, HIV-negative, eligible for tenofovir-based therapy, reports taking therapy no more than 7 days (could have previously taken if has stopped >1 year ago).
Group 2 (acute hbv mono): 18+ years old, HBsAg-positive, HIV-negative, acute/subacute onset of hepatitis signs and symptoms and ALT >10 times upper limit of normal
Group 3 (rx-naive hbv/hiv coinfection): 18+ years old, HBsAg-positive, HIV-negative, eligible for tenofovir-based therapy, reports taking therapy no more than 7 days (could have previously taken if has stopped >1 year ago).
Group 4 (rx-experienced coinfection with hbv persistence): 18+ years old, history of chronic HBV infection based on two tests 6 months apart, HIV-positive, at least 4 years of tenofovir-based antiviral therapy, currently HBsAg-positive
Disqualifiers
Hepatitis C coinfection (antibody-positive and RNA-positive), current or recent (past 6 weeks) pregnancy, decompensated cirrhosis on physical examination, unlikely to remain in Lusaka for study duration
Trial population
This study will occur in Lusaka, Zambia, which has 12% adult HIV prevalence and \~4% adult HBsAg-positivity. Both HIV and HBV treatment are free and provided through the Ministry of Health. Tenofovir-based therapies are used for HBV monoinfection and HBV/HIV coinfection. Potential participants will be recruited from Ministry of Health (i.e., public sector) clinics at study sites including from a pool of participants in past HBV research projects. There are a 5 groups of participants we seek to enroll in the study, to facilitate addressing the scientific goals of the cohort.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
390 Participants
are grouped into 5 trial groupsGroup A: Treatment-naive chronic HBV monoinfection and eligible for antiviral therapy
Group B: Treatment-naive acute HBV monoinfection
Group C: Treatment-naive HBV/HIV coinfection
Group D: Treatment-experienced HBV/HIV coinfection with persistent HBsAg-emia
Group E: Treatment-experienced HBV infection with HBsAg loss
Trial outcomes
Primary outcomes
1
Change in Intrahepatic Immune Cell Subset Frequencies
Percentage of immune cell subsets (CD4+ T cells, CD8+ T cells, B cells, NK cells, Macrophages, and Neutrophils) among total liver immune cells as measured by single-cell RNA sequencing. Comparisons will be made between acute and chronic HBV infection, with and without HIV coinfection, and before and after nucleoside analog antiviral therapy.
Time frame
Baseline and 1 year2
Number of Differentially Expressed Hepatic Genes Associated with HBsAg Reduction/Loss
Count of genes showing differential expression (fold change ≥2.0, adjusted p-value \<0.05) by single-cell RNA sequencing in liver biopsies from participants achieving HBsAg loss compared to those without HBsAg loss. Gene expression will be analyzed at baseline (predictive analysis), longitudinally (trajectory analysis), and at end of follow-up. Analysis will include comparison across acute vs. chronic HBV infection and with vs. without HIV coinfection.
Time frame
Baseline and 1 yearSecondary outcomes
1
HBV viral suppression
Reduction of HBV DNA in blood to below detectable levels
Time frame
Baseline, 1 year, 2 years, 3 years, 4 years, and 5 years2
HIV viral suppression
HIV RNA suppression in blood below the level of assay detection
Time frame
Baseline, 1 year, 2 years, 3 years, 4 years, and 5 years3
HBsAg seroclearance
Loss of hepatitis B surface antigen in blood samples
Time frame
Through study completion, an average of 5 years4
HBeAg seroconversion
HBeAg-negativity in blood
Time frame
Through study completion, an average of 5 yearsSponsors and contacts
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University of Alabama at Birmingham
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
Centre for Infectious Disease Research in Zambia
Collaborator
Tropical Gastroenterology and Nutrition Group
Collaborator
University of Zambia
Collaborator
Massachusetts General Hospital
Collaborator
Weill Medical College of Cornell University
Collaborator
Source ClinicalTrials.gov