Hepatitis B vaccine with TLR-9 agonist achieves high protection in people with HIV

Among people living with HIV (PLHIV), immunization with a hepatitis B surface antigen (HBsAg)-based vaccine adjuvanted with a toll-like receptor (TLR)-9 agonist can induce a 100-percent seroprotection rate, according to a study presented at the recently concluded Virtual ID Week 2022.

Seventy-four PLHIV (median age 47 years, 46 percent men) participated in the prospective, open-label study and were given the hepatitis B virus (HBV) vaccine. The shot was given intramuscularly at a dose of 0.5 mL, containing 200 mcg of recombinant HBsAg and 3,000 mcg of the adjuvant agent. The second and third jabs were given 4 and 24 weeks after the first dose.

Seroprotection, the primary outcome, was defined as the presence of antibodies against the HBsAg at titres ≥10 mIU/mL.

The overall level of HIV control among participants was good. The median CD4 count was 625 cells/mm³, and 96 percent had HIV-1 RNA levels <60 copies/mL. Excluding those who had missed visits or who were followed up beyond the visit window, 68 patients were eventually available for final follow-up. All had received three doses of the HBV vaccine.

Seroprotection was detected in 100 percent of PLHIV, 88 percent of whom achieved antibody titres exceeding the upper limit of the assay (1,000 mIU/mL). Seroprotection rate remained 100 percent in the per-protocol analysis. [ID Week 2022, abstract LB754]

High levels of protection were achieved eight weeks after the second dose, at which point the seroprotection rate was 94.4 percent. Before the third dose, seroprotection rate was 95.5 percent.

“Hepatitis B is a serious liver infection that frequently affects PLHIV,” Judith Currier, MD, of the University of California, Los Angeles, and chair of the AIDS Clinical Trials Group, said in a statement.

“This study shows for the first time that people living with HIV with no history of hepatitis B infection or vaccination were fully protected by this vaccine,” she added.

“Our findings about the protection levels associated with HEPLISAV-B among PLHIV are likely to change clinical practice and have a profound impact on people living with HIV around the world,” Currier said.

In terms of safety, 61 percent of participants experienced at least one adverse event related to the study treatment. Most (39 percent grade 1, 20 percent grade 2) were mild or moderate in severity; only one patient experienced a grade 3 side effect. The most common reaction was vaccination site pain (40 percent), followed by malaise (26 percent) and fatigue (23 percent).

Caution warranted

In another study presented at the Virtual ID Week 2022, researchers looked at the degree of HBV control in PLHIV after switching to a tenofovir-free, two-drug regimen.  

“Many two-drug regimens do not contain tenofovir,” they wrote in their abstract, “and guidelines recommend ensuring patients are not chronically infected with HBV before switching to a tenofovir-free regimen since this could lead to HBV reactivation.”

The retrospective case series included 149 patients who switched to a long-acting injectable cabotegravir and rilpivirine (LAI CAB/RPV) regimen. All patients were negative for HBsAg but positive for the HBV core antigen.

Eventually, 38 patients (7.9 percent) developed low-level HBV viraemia. Two patients were switched back to tenofovir-containing regimens, which suppressed HBV DNA levels. [ID Week 2022, abstract 1583]

The overall clinical significance of HBV reactivation and low-level viraemia remains unknown and warrants further study, the researchers noted. Nevertheless, it also signals caution in this patient population and underlines the need for thoughtful prescription of suppressive regimens, despite the availability of strongly seroprotective vaccines.