Research Summary

Tenofovir Interruptions Linked to Hepatitis B Reactivation Risk in People with HIV in the United States

Edited by:
Kate Young

Key Highlights

  • Tenofovir interruptions were common and often prolonged among people with HIV and HBV in routine US care.
  • HBV DNA and HBsAg monitoring during tenofovir interruption was infrequent, despite near-universal ALT testing.
  • HBV reactivation rates were highest among individuals who were HBsAg-positive at interruption.
  • Reactivation accompanied by hepatitis flare occurred less frequently but was concentrated in the high-risk group.

Tenofovir disoproxil fumarate and tenofovir alafenamide are cornerstone agents for HIV treatment and hepatitis B virus (HBV) coinfection. However, interruptions in tenofovir therapy may place patients at risk for HBV reactivation and hepatitis flares. A new cohort study published in AIDS evaluated the frequency of tenofovir interruptions, associated HBV monitoring practices, and the incidence of HBV reactivation and hepatitis flares among people with HIV and evidence of current or prior HBV infection in the United States.

The investigators analyzed electronic health record data from the Observational Pharmaco-Epidemiology Research & Analysis cohort, which includes patients receiving routine HIV care at 96 clinics across 22 states and one US territory. The study included individuals with HIV who were hepatitis B surface antigen (HBsAg)–positive or hepatitis B core antibody–positive and who experienced at least one interruption of tenofovir lasting 45 days or longer. Interruptions were categorized by serology-based HBV reactivation risk and followed for laboratory monitoring and clinical outcomes.

Study Findings

Among 5,343 individuals with HIV and hepatitis B, the study identified 6,252 tenofovir interruptions between 2001 and 2023. Most interruptions were classified as low risk for HBV reactivation based on serology, while 11% were considered high risk due to HBsAg positivity. Median interruption duration exceeded 20 months, and nearly 4 in 5 interruptions lasted at least 6 months.

Monitoring of HBV during tenofovir interruption was limited. HBV DNA testing occurred during only 11% of interruptions overall and in just over half of high-risk interruptions. HBsAg testing was performed in 28% of interruptions, with little variation across risk groups. In contrast, alanine transaminase testing was conducted during nearly all interruptions.

Reactivation of HBV occurred in 2% of interruptions overall, with marked differences by risk group. Reactivation rates were highest among individuals who were HBsAg-positive at interruption, at 9.92 per 100 person-years. Rates were substantially lower in moderate- and low-risk groups. Hepatitis flares occurred in 5% of interruptions, while HBV reactivation accompanied by flare occurred in 1%, again predominantly in the high-risk group.

Clinical Implications

According to the study authors, the findings suggest that HBV management may be overlooked during routine HIV care in the United States. Although the absolute risk of HBV reactivation was low in individuals without HBsAg, reactivations were observed across all serologic risk groups. The authors noted that incomplete HBV monitoring likely resulted in missed reactivation events, particularly in moderate- and low-risk individuals. Limitations included reliance on observational EHR data, inconsistent laboratory testing, and potential misclassification of baseline HBV risk due to incomplete serologic data.

Expert Commentary

“Primary and HIV care providers must incorporate HBV monitoring in their standard of care and proceed with caution if considering a tenofovir interruption for people with HIV and HBV,” the researchers concluded.

Reference
Dieterich DT, Brunet L, Hsu RK, et al. Monitoring and risk of hepatitis B reactivation and hepatitis flare during tenofovir interruption among people with HIV and hepatitis B. AIDS. 2026;40(1):43-51. doi:10.1097/QAD.0000000000004353