Extra Hep B Vaccine Dose Exceeds Expectations for People With HIV

WASHINGTON -- Three doses of hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG; Heplisav-B) notched a perfect mark when it came to seroprotection for people with HIV who had never before been vaccinated against the hepatitis B virus (HBV), early results of a phase III trial showed.

At 28 weeks, the three doses yielded a 100% (95% CI 94.7-100) rate of seroprotection response -- defined as anti-HBV surface antibody (HBsAb) titers of 10 mIU/mL or greater -- for the 68 evaluable patients in the ongoing trial, reported Kenneth Sherman, MD, PhD, of the University of Cincinnati College of Medicine in Ohio.

Furthermore, 88.2% of participants in the full study population achieved HBsAb titers greater than 1,000 mIU/mL at this time point, some as early as week 4, he told a full house at the annual IDWeek meeting.

The HepB-CpG vaccine was approved as a two-dose regimen for adults in 2017, but little data exist on its protective effects in people with HIV.

"We have known for some time that the efficacy of primary hepatitis B vaccination series using standard non-adjuvanted vaccines in persons living with HIV leads to lower rates of seroprotection," said Sherman, citing rates ranging from 35% to 70%, as compared to 96% for people without HIV.

In the U.S., 10% of people with HIV are co-infected with HBV, putting them at greater risk for liver-related illness and death.

Inspiring the current trial, Sherman explained, was a study of chronic kidney disease patients demonstrating that three doses of HepB-CpG led to "higher levels of seroprotective response that appeared to be maintained for a long period of time."

The findings presented at IDWeek came from early results from group B of the open-label, phase III BEe-HIVe trial, and included 74 adults with HIV who never had an HBV vaccine. (Group A of the study, which is still enrolling, will test two or three doses of HepB-CpG versus three doses of the Engerix-B vaccine in people with HIV who failed to respond to prior HBV vaccination.)

Participants in the current study were recruited from the U.S., Thailand, and South Africa. Their median age was 47 (range 23-68 years), 54% were women, two-thirds were Asian, 16% were Black, and 15% were white. CD4 counts greater than 100 cells/mm³ and use of antiretrovirals for at least 56 days prior to study entry were among the inclusion criteria. At enrollment, participants had a median CD4 count of 625 cells/mm³ and 96% had HIV-1 RNA levels below 60 copies/mL.

Patients were excluded from enrollment if they had a prior HBV infection or a history of hepatic decompensation, solid organ transplantation or other immunocompromising conditions, a cancer diagnosis, or chronic kidney disease.

Patients received three doses of the HepB-CpG vaccine (at study entry, 4 weeks, and 24 weeks), and the primary endpoint was seroprotection response -- HBsAb titers of 10 mIU/mL or greater -- at 28 weeks. Seroprotection response was seen in 30.1% at 4 weeks, 87% at 8 weeks, 94.4% at 12 weeks, and in 98.5% at 24 weeks.

Adverse events related to the vaccine were reported in 61% of participants, the most common being pain at injection site (40%), malaise (26%), fatigue (23%), myalgia (22%), headache (22%), and fever (3%). One female participant became pregnant and had an abortion during the trial, and two participants had serious adverse events (grade 3 suicide ideation; grade 4 depression and a suicide attempt).

Researchers are planning to report durability and safety of the three-dose regimen after an assessment at 72 weeks.

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