People with both Human immunodeficiency virus - the virus which causes HIV/AIDS - and Hepatitis B Virus infections Infections and Infestations HIV/HBV coinfection
Conditions
Interventions
A single arm trial. All eligible participants will temporarily discontinue tenofovir or entecavir whilst continuing their other antiviral medicines. Individuals will be closely followed up for 6 month
Sponsors
King's College Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: 1. HIV-1 antibody and HBsAg positive 2. Receiving 2.1. Dolutegravir + tenofovir disoproxil fumarate/tenofovir alafenamide + lamivudine/emtricitabine, OR 2.2. Darunavir with cobicistat/ritonavir + tenofovir disoproxil fumarate/tenofovir alafenamide + lamivudine/emtricitabine, OR 2.3. Other antiretroviral combination including lamivudine/emtricitabine and tenofovir disoproxil fumarate/tenofovir alafenamide, where discontinuation of tenofovir would not be expected to lead to loss of HIV control*, OR 2.4. A tenofovir-free antiretroviral combination including lamivudine/emtricitabine, plus entecavir 3. Antiretroviral regimen stable for =6 months 4. HBV DNA 350 c/mm³ 10. No significant hepatic fibrosis (Fibroscan =6kPa or liver biopsy <F2) 11. Provides written, informed consent 12. Age 18 years or older 13. Is willing to comply with protocol requirements 14. Is willing to use condoms or abstain during the trial * This will be determined at the investigator’s discretion
Exclusion criteria
Exclusion criteria: 1. Other viral hepatitis coinfection including HDV antibody positive or HCV antigen or HCV RNA positive. Note HCV antibody positive with RNA or antigen negative is permitted. 2. History of known or suspected HBV resistance 3. History of HIV resistance to nucleos(t)ide reverse transcriptase inhibitors or integrase strand transfer inhibitors or protease inhibitors, where the resistance could be expected to compromise the efficacy of the tenofovir-free regimen 4. HIV-2 5. Non-viral hepatitis liver comorbidity including alcohol-associated, metabolic or autoimmune 6. Fibroscan >6kPa or liver biopsy =F2 7. ALT > 40 IU/L 8. Less than 18 years old 9. Pregnancy or breastfeeding 10. History of hepatocellular carcinoma 11. Any malignancy within previous 2 years, other than skin basocellular carcinoma 12. Non-HIV immunodeficiency including organ transplantation or medication-induced immunosuppression within previous 6 months 13. Any medical condition, including neurological or psychiatric conditions, which in the judgement of the investigator may impair a volunteer’s ability to give informed consent or attend study visits
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility of temporary simplification of antiviral therapy in HIV/HBV coinfection as determined at 24 weeks by: 1. % of those approached who agree to be assessed for eligibility 2. % of those screened with undetectable HBV pgRNA 3. % of those screened with undetectable HBcrAg 4. % of those eligible after screen who consent to the study 5. % of those participating at 24 weeks 6. % of those with Adverse Events by 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of individuals with a liver enzyme ALT or AST increase > 3x the level at the baseline visit, or >120 U/L, at baseline and weeks 2, 4, 8, 12, 16, 20, 24 2. Proportion of individuals with an HBV DNA level >20 IU/ml at baseline and weeks 2, 4, 8, 12, 16, 20, 24 3. Proportion of individuals with an HBV DNA level >200 IU/ml at baseline and weeks 2, 4, 8, 12, 16, 20, 24 4. Proportion of individuals with an HIV-1 RNA level >50 c/ml at weeks 4, 12 and 24 5. Proportion of individuals with an HIV-1 RNA level >200 c/ml at weeks 4, 12 and 24 6. Proportion of individuals remaining on simplified therapy at 24 weeks 7. HBsAg levels at baseline and weeks 12 and 24 8. HBV pgRNA levels at baseline and weeks 12 and 24 9. HBcrAg levels at baseline and weeks 12 and 24 10. Quality of life assessed through questionnaires at baseline and 24 weeks | — |
Countries
England, United Kingdom
Outcome results
None listed