Anti-HBs Seroconversion Following Withdrawal of Anti-HBV-Active Agents: An Underrecognized Form of HBV Reactivation?

To the Editor—We read with great interest the study by Foncillas et al evaluating the risk of hepatitis B virus (HBV) reactivation (HBVr) or incident infection in people with HIV (PWH) switching cabotegravir/rilpivirine (CAB/RPV) [1]. Notably, no HBVr cases were reported among individuals without chronic hepatitis B, including those with isolated anti-HBc positivity (3% of the cohort). However, HBVr after switching to CAB/RPV in individuals with isolated anti-HBc positivity has been documented. One reported case involved waning anti-HBs levels followed by hepatitis B surface antigen (HBsAg)–positive reactivation and chronic infection after discontinuing tenofovir [2]. Our case differs: Instead of HBsAg reappearance, we observed a sudden, marked anti-HBs seroconversion. While not meeting the formal definition of HBVr, this likely reflects subclinical reactivation triggered by the withdrawal of anti-HBV-active agents. We report a case of a man in his 60s, a man who has sex with men with HIV, diagnosed with HIV/AIDS 20 years ago following Pneumocystis pneumonia. At presentation, his CD4 count was 55 cells/μL with negative HBsAg and anti-HBs (4.44 mIU/mL), and no history of HBV vaccination. Antiretroviral therapy (ART) was initiated with zidovudine/lamivudine (AZT/3TC) plus ritonavir-boosted atazanavir. Anti-HBc positivity was subsequently identified, consistent with isolated anti-HBc positivity, and the regimen was later switched to tenofovir disoproxil fumarate/3TC plus boosted atazanavir. Over time, ART was further modified, including tenofovir-sparing regimens, although 3TC was maintained. Fifteen years after diagnosis, ART was switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).