Claudia Hawkins1, Minhee Kang2, Debika Bhattacharya3, Gavin Cloherty4, Mary Kuhns4, Roy Matining2, Chloe Thio5, Wadzanai Samaneka6, Lameck Chinula7, Nyirenda Mulinda8, Sharlaa Badal-Faesen9, Patcharaphan Sugandhavesa10, Javier Lama11, Simani Gaseitsiwe9, Vera Holzmayer4, Mark Anderson4, Robert Murphy1, Marion Peters1. 1. Department of Medicine, Feinberg School of Medicine, Northwestern University CRS, Chicago, Illinois. 2. Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 3. David Geffen School of Medicine, Division of Infectious Diseases, University of California, Los Angeles (UCLA), California. 4. Infectious Diseases Research, Abbott, Abbott Park, Illinois. 5. Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. 6. University of Zimbabwe Clinical Trials Research Centre, Zimbabwe. 7. UNC Project Malawi CRS, UNC Department of Obstetrics and Gynecology's Division of Global Women's Health, Chapel Hill, North Carolina, USA. 8. Malawi College of Medicine- Johns Hopkins Research Project CRS. 9. Clinical HIV Research Unit, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 10. Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand. 11. Asociacion Civil Impacta Salud y Educacion, Lima, Peru, and Botswana Harvard School of Public Health AIDS Initiative Partnership, Botswana.
Abstract
INTRODUCTION: With advances in hepatitis B virus (HBV) therapies, there is a need to identify serum biomarkers that assess the HBV covalently closed circular DNA (cccDNA) reservoir and predict functional cure in HIV/HBV co-infection. METHODS: In this retrospective study, combining samples from HIV/HBV co-infected participants enrolled in two ACTG interventional trials, proportions achieving HBsAg less than 0.05 log10 IU/ml and HBV RNA less than log10 1.65 U/ml or not detected (LLoQ/NEG) in response to DUAL [tenofovir TDF+emtricitabine (FTC)] vs. MONO [FTC or lamivudine (3TC)] HBV-active ART, were measured. Predictors of qHBsAg less than 0.05 log10 IU/ml were evaluated in logistic regression models. RESULTS: There were 88 participants [58% women, median age 34; 47 on DUAL vs. 41 on MONO HBV-active ART]. Twenty-one percent achieved HBsAg less than 0.05 log10 IU/ml (30% DUAL vs. 10% MONO). Time to HBsAg less than 0.05 log10 IU/ml was lower (P = 0.02) and the odds of achieving HBsAg less than 0.05 log10 IU/ml were higher (P = 0.07) in DUAL participants. HBV RNA became less than LLoQ/NEG in 47% (DUAL 60% vs. MONO 33%). qHBsAg less than 3 log10 IU/ml was the strongest predictor of HBsAg less than 0.05 log10 IU/ml. CONCLUSION: This study supports current recommendations of TDF-based DUAL-HBV active ART for initial use in HIV/HBV co-infection. HBV RNA could be a useful marker of treatment response in HIV/HBV co-infected patients on HBV-active ART.
INTRODUCTION: With advances in hepatitis B virus (HBV) therapies, there is a need to identify serum biomarkers that assess the HBV covalently closed circular DNA (cccDNA) reservoir and predict functional cure in HIV/HBV co-infection. METHODS: In this retrospective study, combining samples from HIV/HBV co-infected participants enrolled in two ACTG interventional trials, proportions achieving HBsAg less than 0.05 log10 IU/ml and HBV RNA less than log10 1.65 U/ml or not detected (LLoQ/NEG) in response to DUAL [tenofovir TDF+emtricitabine (FTC)] vs. MONO [FTC or lamivudine (3TC)] HBV-active ART, were measured. Predictors of qHBsAg less than 0.05 log10 IU/ml were evaluated in logistic regression models. RESULTS: There were 88 participants [58% women, median age 34; 47 on DUAL vs. 41 on MONO HBV-active ART]. Twenty-one percent achieved HBsAg less than 0.05 log10 IU/ml (30% DUAL vs. 10% MONO). Time to HBsAg less than 0.05 log10 IU/ml was lower (P = 0.02) and the odds of achieving HBsAg less than 0.05 log10 IU/ml were higher (P = 0.07) in DUAL participants. HBV RNA became less than LLoQ/NEG in 47% (DUAL 60% vs. MONO 33%). qHBsAg less than 3 log10 IU/ml was the strongest predictor of HBsAg less than 0.05 log10 IU/ml. CONCLUSION: This study supports current recommendations of TDF-based DUAL-HBV active ART for initial use in HIV/HBV co-infection. HBV RNA could be a useful marker of treatment response in HIV/HBV co-infected patients on HBV-active ART.
Authors: Emily K Butler; Jeffrey Gersch; Anne McNamara; Ka-Cheung Luk; Vera Holzmayer; Maria de Medina; Eugene Schiff; Mary Kuhns; Gavin A Cloherty Journal: Hepatology Date: 2018-09-22 Impact factor: 17.425
Authors: Jennifer Audsley; Anchalee Avihingsanon; Margaret Littlejohn; Scott Bowden; Gail V Matthews; Christopher K Fairley; Sharon R Lewin; Joe Sasadeusz Journal: J Acquir Immune Defic Syndr Date: 2020-08-15 Impact factor: 3.731
Authors: Michael J Vinikoor; Edford Sinkala; Roma Chilengi; Lloyd B Mulenga; Benjamin H Chi; Zude Zyambo; Christopher J Hoffmann; Michael S Saag; Mary-Ann Davies; Matthias Egger; Gilles Wandeler Journal: Clin Infect Dis Date: 2017-05-15 Impact factor: 9.079