In HIV patients who failed to achieve protection from the hepatitis B virus (HBV) vaccine, a high-dose revaccination schedule led to better serological responses versus standard dosing, a randomized single-center trial in Chile showed.

In an intention-to-treat analysis involving over 100 patients, 72% of those revaccinated with three doses of a high-dose recombinant HBV vaccine achieved serological response compared to 51% of those given a standard-dose regimen (OR 2.48, 95% CI 1.02-6.10, P=0.03), reported Jose Ignacio Vargas, MD, of the Pontifical Catholic University of Chile in Santiago, and colleagues.

At 1 year, twice as many patients in the high-dose arm had antibody titers in the protective range (>10 IU/L) than those in the standard-dose arm (80% vs 39%, respectively; P=0.01), the group wrote in JAMA Network Open.

The double-masked CORE-HIV (HBV Comparative Revaccination in HIV) study included 107 adults with HIV who had an inadequate response to HBV vaccination (<10 IU/L). Patients were randomized 1:1 to accelerated vaccination schedules of the standard (20 μg) or high dose (40 μg) Engerix-B HBV vaccine — administered at 0, 1, and 2 months.

“We believe that the high-dose with shorter interval schedule used in this study could be considered as one of the primary options in stable patients with HIV for HBV revaccination,” the authors concluded. “Given the lower rate of serological response of the standard HBV vaccination regimen at monthly intervals used in our study, this regimen should probably not be recommended for HBV revaccination in patients with HIV.”

In an accompanying editorial, Amir Mohareb, MD, and Arthur Kim, MD, both of Massachusetts General Hospital in Boston, explained that “people with HIV who are exposed to HBV have a higher likelihood of progressing to chronic infection, which is associated with progressive liver disease, hepatocellular carcinoma, and liver-related mortality.”

They added that “HBV vaccination remains an important and effective means of prevention for people with HIV, even though a substantial proportion of patients do not respond to an initial vaccine series.”

But Mohareb and Kim highlighted how in the current trial, “nearly all participants had normal creatinine and aminotransferase levels,” and nearly all were on antiretroviral therapy (ART) with undetectable HIV RNA levels.

As prior trials have shown benefit of a double-dose regimen with a four-dose — but not three-dose — series, “clinicians may still need to defer to the four-dose series or to other HBV vaccination strategies in their patients with more comorbidities or evidence of immunodeficiency,” they said.

Study Details

All participants were treated at Hospital Dr Gustavo Fricke, an outpatient clinic in Chile, from December 2013 to March 2018. Patients were excluded if they had serological markers for HBV. Follow-up occurred at 4 to 8 weeks, and at 1 year following the third vaccine dose. Serological response to vaccination was the primary outcome, evidenced by hepatitis B surface antibodies (anti-HBs) greater than 10 IU/L at 4 to 8 weeks post-vaccination.

At 4 to 8 weeks, average anti-HB titers were more than twice as high in the 40-μg group than in the 20-μg group (398 vs 158 IU/L; P<0.001). And more patients in the high-dose group had anti-HB titers over 100 IU/L compared to the standard-dose group (80.6% vs 50.5%; P=0.02).

“Postvaccination monitoring of anti-HBs titers may still be warranted, especially in patients with ongoing risk of HBV acquisition or who may not be receiving treatment with HBV-active ART,” the editorialists noted.

Mean participant age was 47 and three-fourths were male. Nearly all patients received ART (98%) and most had undetectable HIV viral loads (86%). Average patient CD4+ cell count was 418, one patient had hepatitis C, and 60% had dyslipidemia. Patients were living with HIV for a median of 85 months and taking ART for a median of 56 months.

Study limitations included the lack of patient diversity, that some institutions use a different vaccination schedule (0, 1, and 6 months) than the control arm, and that low responses in the standard arm may have factored into the significant between-arm difference, the authors acknowledged.