Hepatitis B, HIV
Conditions
Keywords
HBV/HIV coinfection, HBV immunology, Liver sampling, Africa, Tenofovir, T cell immunology, Omics analysis, Acute HBV infection, Liver immunology
Brief summary
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.
Interventions
None listed
Sponsors
University of Alabama at Birmingham
National Institute of Allergy and Infectious Diseases (NIAID)
Centre for Infectious Disease Research in Zambia
Tropical Gastroenterology and Nutrition Group
University of Zambia
Massachusetts General Hospital
Weill Medical College of Cornell University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Must meet the inclusion criteria for one of 5 groups, as follows: * 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 * Group 5 (hbsag loss): 18+ years old, HIV-positive or negative, history of chronic HBV infection based on two tests 6 months apart, Currently HBsAg-negative confirmed by sensitive assay
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intrahepatic Immune Cell Subset Frequencies | Baseline and 1 year | 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. |
| Number of Differentially Expressed Hepatic Genes Associated with HBsAg Reduction/Loss | Baseline and 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HBeAg seroconversion | Through study completion, an average of 5 years | HBeAg-negativity in blood |
| HBV viral suppression | Baseline, 1 year, 2 years, 3 years, 4 years, and 5 years | Reduction of HBV DNA in blood to below detectable levels |
| HIV viral suppression | Baseline, 1 year, 2 years, 3 years, 4 years, and 5 years | HIV RNA suppression in blood below the level of assay detection |
| HBsAg seroclearance | Through study completion, an average of 5 years | Loss of hepatitis B surface antigen in blood samples |
Countries
Zambia
Contacts
CONTACTMichael J Vinikoor, MD
CONTACTIke Oyewole
PRINCIPAL_INVESTIGATORMichael Vinikoor, MD
University of Alabama at Birmingham
Outcome results
None listed