PARIS — People with HIV and resolved HBV infection who switched from tenofovir-based antiretroviral therapy (ART) to tenofovir-sparing regimens did not see clinically meaningful hepatitis B virus (HBV) reactivation, a major analysis from the Swiss HIV Cohort Study has reported.

Presenting the findings at the European AIDS Clinical Society (EACS) 2025 Annual Meeting, Lorin Begré, MD, PhD, Department of Infectious Diseases, Bern University Hospital, Bern, Switzerland, said, “These findings are reassuring for hepatitis B core antibody [anti-HBc]-positive, hepatitis B surface antigen [HBsAg]-negative people with HIV and their physicians that switching to non-tenofovir-based ART is possible.”

Up to 30% of people living with HIV have anti-HBc antibodies, indicating past HBV infection. Begré noted that understanding who may be at risk for HBV reactivation has become essential with the growing adoption of dual-drug and long-acting injectable ART regimens that do not contain the HBV treatment tenofovir.

HBV Reactivation Below Limits of Quantification

The study included 380 matched participants from the Swiss HIV Cohort Study who were anti-HBc-positive and HBsAg-negative and had switched from tenofovir-containing ART. Participants were grouped according to whether they transitioned to non-HBV-active regimens or to lamivudine/emtricitabine-containing ART, with matching on the basis of age, sex at birth, and duration of prior tenofovir therapy. Stored plasma samples were assessed at baseline and at least 1 year after therapy modification.

A two-step HBV DNA detection method was employed. This consisted of a highly sensitive qualitative screening assay, with a limit of detection of approximately 1.2 IU/mL, followed by quantitative polymerase chain reaction (PCR) for positive samples. Researchers also monitored HBsAg status, anti-HBc titers, and HBV RNA using both commercial and research-use assays.

The median age of participants was 50 years, with women comprising approximately 25% of the cohort. Median duration on tenofovir was 4.5 years. All participants were HBV RNA-negative at baseline, and five had detectable but nonquantifiable HBV DNA prior to switching.

Following at least 1 year of follow-up, 1.6% of participants on non-HBV-active regimens and 1.1% of those on lamivudine/emtricitabine-containing regimens had detectable HBV DNA, reported Begré. However, none showed quantifiable HBV DNA on PCR; all cases remained below the threshold of clinical concern, and all remained HBV RNA-negative. HBsAg remained negative among all participants who had detectable HBV DNA.

Begré emphasized that, although some virologic signs of reactivation were observed, all remained below the limit of quantification and posed no clinical consequence. He acknowledged that participants switching to non-HBV-active ART were more likely to restart tenofovir within a year, although this was not linked to clinically meaningful reactivation.

Other Data on Switch to Tenofovir-Free Regimens

Commenting on the broader implications, Sanjay Bhagani, MD, professor and consultant physician in infectious diseases/HIV medicine at the Royal Free London NHS Foundation Trust and University College London, London, England, said these findings are consistent with other data presented at the conference. He noted that oral abstract PS01.4 from Barcelona reported no cases of clinically significant HBV reactivation or new infection following switches to tenofovir-free regimens such as long-acting cabotegravir/rilpivirine.

According to Bhagani, while a small proportion of individuals showed evidence of occult HBV replication (HBsAg-negative, HBV DNA-positive), the proportions were very low, generally 1%-2%, and did not result in clinically relevant disease or liver injury. “This is very reassuring for clinicians in the field,” he said.

Bhagani highlighted that, in practice, “these findings support switching anti-HBc-positive, HBsAg-negative individuals to tenofovir-sparing regimens when it reduces pill burden, addresses stigma related to daily oral therapy, or mitigates long- and short-term toxicity.”

He noted that hepatitis B vaccination remains essential for individuals without anti-HBs antibodies when switching and that regimens retaining lamivudine or emtricitabine generally require no special monitoring.

“For those transitioning to regimens without HBV-active components, periodic liver enzyme testing with subsequent HBsAg and HBV DNA testing if elevated may be advisable.”

He also stressed that tenofovir- or entecavir-containing therapy currently remains the cornerstone of therapy for HBsAg-positive individuals.

“The findings from this study are reflected in current EACS guidelines and reinforce confidence in tenofovir-sparing strategies among appropriately selected patients,” said Bhagani.

Another poster presented at EACS 2025 reflected the findings of the study by Begré entitled “Kinetics of Occult Hepatitis B Infection in People With HIV Switching From HBV-Active ART to Long-Acting Cabotegravir/Rilpivirine.”

Begré reported receiving research support from Roche Diagnostics and Gilead Sciences. Bhagani reported receiving research funding or support from AbbVie, Gilead Sciences, MSD, and ViiV/GSK.