Challenges and Controversies

There are several reasonable answer choices here, and the Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV list both a 2-shot series of Heplisav-B and a 3-shot series of double-dose Recombivax-HB or Engerix-B as options for vaccine non-responders. In the situation presented, it is not clear if the patient never mounted an antibody response to the primary HBV vaccine series, or if he simply had waning anti-HBs levels over time (I suspect the latter). In the case of waning anti-HBs levels, the option to revaccinate with 1 dose of an HBV vaccine and check an anti-HBs level in 1-2 months would also be reasonable, particularly if he had a robust CD4 count. In general, however, I would favor revaccinating with 2 doses of the Heplisav-B vaccine given the high rates of seroprotection (e.g., anti-HBs ≥10 mIU/mL) afforded by this vaccine in both clinical trials and retrospective analyses of persons living with HIV (PLWH). I will note that while a recent study of Heplisav-B in HBV vaccine-naive PLWH (the Bee-HIVe trial) found a 100% seroprotection rate after 3 doses of Heplisav-B, rates of seroprotection were nearly has high (98.5%) after only two doses, and therefore, I do not think a 3rd dose would be needed here.

It is important to ensure HBV immunity in persons with HIV (PWH) since they remain at risk of progressing to chronic infection and experiencing liver-related complications once infected. So the answer is definitely not “Do not revaccinate.” It cannot be assumed that PWH will mount an anamnestic response as their functional HBV immunity (natural or vaccine-acquired) may be impaired. There are two possibilities for lack of anti-HBs in this individual: (1) There was an initial seroprotective response to childhood immunization but the anti-HBs antibody level has waned over time (a well-known phenomenon that may or may not indicate loss of HBV immunity in PWH) or (2) this individual never responded to his initial childhood vaccination series, which can occur in up to 5-10% who receive their initial series. In the case of (2), it is generally recommended that individuals be revaccinated with a different vaccine series as up half of non-responders will respond the 2nd time around. You do have the option of giving a dose and testing for anamnestic response (which would suggest scenario 1) or just completing a series. The ACTG BEe-HIVe trial showed that Heplisav-B resulted in very high seroprotective response rates with robust anti-HBs titers in naive PWH so I favor using this vaccine over the standard recombinant (which this patient has already had).