Liver Fibrosis in Zambian HIV-HBV Co-infected Patients

Study Overview
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Brief Summary
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In this study the investigators will determine risk factors for liver fibrosis among HIV-HBV co-infected patients in Lusaka, Zambia, and assess the long-term effectiveness of antiretroviral drugs in the prevention and/or reduction of liver disease.

Detailed Description
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Among HIV-infected individuals in Africa, liver disease is a neglected area of investigation but is anticipated to become increasingly common as patients live longer due to antiretroviral therapy. In a currently approved and active research study taking place in Lusaka Urban district - HIV/HBV co-infection in IeDEA-SA (NCT02060162, clinicaltrials.gov) - 800 consecutive HIV-infected adults were screened for possible causes of liver disease and 12% were diagnosed with chronic hepatitis B virus (HBV) co-infection. HBV co-infected patients were more likely to have evidence of liver disease; however, ascertainment of critical long-term outcomes of HIV-HBV patients was not part of the study. Building on these preliminary results and addressing the need to study HIV-HBV during a longer duration of follow-up, the current protocol will focus exclusively on Zambian HIV-HBV patients. In the proposed study, the investigators will determine the risk factors for liver disease among Zambian HIV-HBV co-infected patients, and assess the long-term effectiveness of Ministry of Health (MOH)-recommended antiretroviral drugs in the prevention and/or reduction of HIV-HBV liver disease. This study will provide useful clinical and epidemiologic information to health policymakers in Zambia and throughout the region and may lead to improvements in the care of HIV-HBV patients. Further, it will strengthen collaboration between Zambian institutions and strengthen local capacity in HBV diagnosis and management.

Official Title
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Liver Fibrosis in Zambian HIV-HBV Co-infected Patients: a Long-term Prospective Cohort Study

Conditions
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Fibrosis, Liver, HBV, Human Immunodeficiency Virus, Cirrhosis, Liver, Hepatocellular Carcinoma, Hepatitis Delta Virus, Alcoholic Hepatitis

Intervention / Treatment
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* Drug: Anti-HIV Agents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older HIV-infected HBV-infected, defined as any single positive HBsAg assay Naïve to antiretroviral therapy or currently participating in HIV/HBV co-infection in IeDEA-SA Exclusion Criteria: Unable or unwilling to provide informed consent Planning to relocate out of Lusaka district

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV-HBV co-infected<br>HIV-HBV co-infected patients receiving anti-retroviral therapy | Drug: Anti-HIV Agents<br> <br> * Other names: Anti-retroviral therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in liver fibrosis stage | Measure of liver fibrosis using AST-to-platelet ratio index (APRI), Fibrosis 4 (FIB-4) and transient elastography. Ascertainment of potential risk factors including demographics, alcohol use, HIV-related biomarkers, HBV DNA, hepatitis delta virus, and other factors. | From baseline to month 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of hepatocellular carcinoma | Liver cancer screening at baseline and during follow-up | From baseline to month 48 | 
| Prevalence of significant liver fibrosis (Metavir F2 or greater) | Measure of liver fibrosis using AST-to-platelet ratio index (APRI), Fibrosis 4 (FIB-4) and transient elastography | At enrollment | 
| Risk factors for persistent HBV viremia 9Measure HBV DNA at baseline and month 12 and determine patient characteristics associated with unsuppressed HBV after 12 months of treatment) | Measure HBV DNA at baseline and month 12 and determine patient characteristics associated with unsuppressed HBV after 12 months of treatment | Month 12 |