Background: Tenofovir and HBV in HIV Care
Tenofovir has been a cornerstone of antiretroviral therapy (ART) for people living with HIV, partly because it also provides activity against hepatitis B virus (HBV). For patients with past HBV exposure who are virologically suppressed, clinicians have explored strategies to reduce long-term drug toxicity—especially renal and bone side effects—by switching to tenofovir-sparing regimens. A key question has been whether stopping tenofovir could trigger HBV reactivation in people who are HBsAg-negative but HBcAb-positive (indicating past exposure to HBV).
New Data from the Swiss HIV Cohort Study
New late-breaking findings presented at the 2025 European AIDS Clinical Society (EACS) Congress address this question directly. In the Swiss HIV Cohort Study, researchers investigated HBcAb-positive, HBsAg-negative participants who transitioned from tenofovir-containing ART to regimens without HBV-active agents. The switch was evaluated in 380 participants after a median of 4.5 years on tenofovir, with a 1:1 match to controls remaining on regimens that included HBV-active agents (XTC-containing ART).
Methods: High-Sensitivity HBV DNA Testing
Stored plasma samples were analyzed before withdrawal and after switch using high-sensitivity HBV DNA assays. The aim was to detect any reactivation of HBV at very low levels and to correlate these findings with clinical outcomes and liver enzyme tests.
Key Findings: Very Low Reactivation Risk
Before stopping tenofovir, a small fraction of participants—about 1–2%—had detectable HBV DNA, consistent with low-level reactivation risk in a population with past HBV exposure. After a median follow-up of 1.3 years post-switch, HBV DNA was detected in 5.3% of those who moved to non-XTC (no HBV-active agents) regimens, compared with 1.6% of those who remained on XTC-containing ART (p=0.048). Importantly, all detectable HBV DNA results were below the quantification threshold, indicating ultralow viral activity rather than clinically meaningful replication.
HBV Markers and Clinical Safety
Among HBcAb-positive participants who switched to non-tenofovir therapy, 3.4% showed any detectable HBV DNA at follow-up. Crucially, none of these cases progressed to significant hepatitis or required medical intervention. Liver enzyme elevations were similar between groups with and without detectable HBV DNA, suggesting that low-level reactivation did not translate into hepatic injury in this cohort.
Clinical Implications: Safety of Tenofovir-Sparing ART
The findings provide reassuring real-world evidence that HBV reactivation is uncommon and generally clinically insignificant when virologically suppressed people with HIV transition to tenofovir-sparing ART. This is particularly relevant for aging populations where the renal and bone toxicities of long-term tenofovir use are of concern, and where reducing exposure to tenofovir could improve quality of life and overall health outcomes.
Context for ART Strategy
These results support growing confidence in flexible ART designs that de-emphasize lifelong exposure to HBV-active agents when safe to do so. Careful patient selection remains essential, with attention to HBV status, liver disease stage, and other risk factors. The data also underscore the value of maintaining HBV marker monitoring after switching, especially for individuals with advanced liver disease or additional risk factors for reactivation.
Practical Takeaways for Clinicians and Patients
- For HBsAg-negative/HBcAb-positive people with HIV who are virologically suppressed, stopping tenofovir and switching to a non-HBV-active regimen shows a very low rate of HBV DNA detection after about a year, and no progression to hepatitis in the study cohort.
- Switching to tenofovir-sparing ART can reduce long-term drug toxicity without introducing meaningful HBV-related safety concerns for most patients.
- Ongoing monitoring of HBV markers remains prudent, especially for those with advanced liver disease or other risks.
Reference: Begré L et al. Low risk of HBV reactivation in HBcAb-positive/HBsAg-negative persons with HIV switching to non-tenofovir-based antiretroviral therapy. PS15.6.LB. EACS 2025, 15-18 October, 2025.
