Hepatitis B virus replication during tenofovir therapy is frequent in HIV/HBV coinfection. Clinical Infectious Diseases
Hofmann et al. analyzed rates of hepatitis B virus (HBV) suppression with tenofovir-containing antiretroviral therapy (ART), and assessed determinants for ongoing HBV replication despite treatment among people living with HIV and HBV in the Swiss HIV Cohort Study (SHCS).
The present study included all cohort participants with chronic HBV infection. The authors evaluated HBV replication at 2 years and at the latest available follow-up (categorized as suppression if HBV DNA was <20 IU/mL, low-level viremia if HBV DNA was 20-2000 IU/mL, and high-level viremia if HBV DNA was >2000 IU/mL). Risk factors for persistent viral replication (HBV DNA >20 IU/mL) were assessed using multivariable logistic regression.
The study population consisted of 222 individuals with HIV/HBV coinfection on tenofovir-containing ART. The median age was 41 years (IQR 36-47), 19% were female, 21% were of African origin, and 59% had been previously treated with lamivudine- or emtricitabine-containing ART. After 2 years of tenofovir, 61/222 (27%) had persistent HBV replication. Persistent HBV replication was more common among individuals with high HBV-DNA at tenofovir start (adjusted odds ratio [aOR] 1.38, 95% CI 1.20-1.57), and less likely among patients with a CD4 cell count >350cells/μL (aOR 0.41, 0.19-0.90), among people with hepatitis D coinfection (aOR 0.07, 0.01-0.59) and those with good self-reported ART adherence (aOR 0.04, 0.01-0.33). Of the 61 individuals with a replicating HBV infection at 2 years, 14 (23%) had persistent replication at the latest follow-up visit (median 8.4 years after starting tenofovir).
In summary, this work shows that ongoing HBV replication is frequent after 2 years of tenofovir-containing ART, especially in individuals with a high HBV viral load at tenofovir start and suboptimal ART adherence. In contrast, HDV coinfection was associated with higher rates of HBV suppression. As 77% of individuals eventually achieved HBV viral suppression during follow-up, replication after 2 years does not necessarily imply treatment failure. As ongoing viral replication contributes to liver fibrosis and to the development of hepatocellular carcinoma, these findings highlight the importance of continued follow-up of individuals with HIV/HBV coinfection.