Long-Term TDF-Inclusive ART and Progressive Rates of HBsAg Loss in HIV-HBV Coinfection-Lessons for Functional HBV Cure?
Jennifer Audsley 1 , Anchalee Avihingsanon, Margaret Littlejohn, Scott Bowden, Gail V Matthews, Christopher K Fairley, Sharon R Lewin, Joe Sasadeusz
Affiliations
Affiliation
1
aThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia; bDepartment of Infectious Diseases, The Alfred Hospital and Monash University, Melbourne, Australia; cHIV-NAT, Thai Red Cross AIDS Research Centre and Tuberculosis Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; dVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Australia; eThe Kirby Institute, Sydney, Australia; fDepartment of Infectious Diseases, St Vincent's Hospital, Sydney, Australia; gMelbourne Sexual Health Centre, Alfred Health, Melbourne, Australia; hCentral Clinical School, Faculty of Medicine, Monash University, Melbourne, Australia; and iVictorian Infectious Disease Service, Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Australia.
PMID: 32692112 DOI: 10.1097/QAI.0000000000002386
Abstract
Background: Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and hepatitis B virus (HBV) replication in HIV-HBV coinfection although HBV DNA can persist in some individuals on TDF-containing antiretroviral therapy (ART). We initiated a prospective longitudinal study to determine durability of HBV virological control and clinical outcomes after prolonged TDF-based ART in HIV-HBV coinfection.
Methods: Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing ART from Australia (n = 41) and Thailand (n = 52) were enrolled. Participants were followed 6-monthly for 2 years, then annually to 5 years. Laboratory and clinical assessments and a serum sample were collected at each study visit. These analyses compare follow-up at 2 and 5 years.
Results: 12.0% (95% confidence interval 6.8 to 20.2) of total study entry cohort (n = 92) or 15.3% (95% confidence interval: 8.8 to 25.3) of those with data to year 5 (n = 72) lost hepatitis B surface antigen (HBsAg). The only statistically significant association with HBsAg loss was lower study entry quantitative HBsAg. CD4 T-cell count increased by a median 245 cells/mm3 between the preTDF sample and 5 years of follow-up. By year 5, 98.5% of the cohort had undetectable HBV DNA (<15 IU/mL) and 91.4% had undetectable HIV RNA (<20 copies/mL).
Conclusions: HBsAg loss was high and ongoing over 5 years of follow-up in HIV-HBV coinfected individuals on TDF-containing ART and undetectable HBV was almost universal. Although the pattern of HBsAg loss temporarily parallels immune reconstitution, we could not identify predictive immune markers. The high rate of HBsAg loss in HIV-HBV coinfection may offer valuable insights into the search for a functional HBV cure. 作者: StephenW 时间: 2020-7-22 13:21