Three-Dose Hepatitis B Vaccine Regimen Can Protect Those With HIV

Historically, persons living with HIV (PLWH) have relatively poor responses to hepatitis B virus (HBV) vaccination with seroprotection rates ranging from 35%-70% following a 3-dose series.

However, a new study found that a 3-dose course of the hepatitis B vaccine HEPLISAV-B fully protected adults living with HIV who had never been vaccinated against or infected with the HBV.

“This study was designed to study the effectiveness of HEPLISAV-B, which is a newer vaccine product that contains recombinant HB surface antigen and a CPG based Toll-like 9 receptor agonist,” said study chair Kenneth E. Sherman, MD, PhD, of the University of Cincinnati College of Medicine in Ohio. “Two main groups with HIV infection are under evaluation. The first are those who failed to respond to prior vaccination efforts with standard HBV vaccines and the other group are HBV vaccine naïve.”

He explained that HBV is spread primarily through sexual contact and sharing of contaminated needles, causing chronic hepatitis B infection which can lead to progressive liver disease. People living with HIV, including those who are taking antiretroviral therapy, are at greater risk of liver-related illness and death when co-infected with HBV.

The ACTG 5379 clinical trial was developed and implemented by the AIDS Clinical Trials Group (ACTG) which is funded by the National Institute of Allergy and Infectious Diseases (NIAID)at the Natoinal Institutes of Health.

Beverly Alston-Smith, MD, chief of the complications and co-infections research branch within NIAID’s division of AIDS, noted while HBV is largely preventable with vaccination, chronic HBV infection is difficult to treat and may require lifelong treatment.

“It is important to develop HBV vaccines that are efficacious for all, especially those at high risk of infection or known have a less response to vaccines,” she said.

The researchers tested a 3-dose course (at weeks 0, 4, and 24) of HEPLISAV-B among 68 adults living with HIV at 38 sites in the United States, South Africa, and Thailand. None had a history of HBV vaccination or evidence of prior HBV exposure. Participants achieved 100% seroprotection.

Alston-Smith noted she was surprised by the 100% seroprotection rates as previous studies of vaccination in PLWH had rates in the 30%-70% range.

“No unexpected safety issues were observed,” she said. “This is the first clinical trial to show high seroprotection rates with HEPLISAV-B in persons living with HIV.”

The authors presented their findings at the Infectious Disease Society of America, focusing on the latter group, and presented data through week 28 (4 weeks post third dose). The results were powered and compared to historical controls from a prior ACTG vaccine study. In the vaccine naïve group, 100% achieved effective anti-HBs titers for seroprotection after 3 doses. After 2 doses and before the third, 98.5% achieved protection.

At 8 weeks after the second dose, 94.4% of participants achieved seroprotection; this percentage increased to 98.5% by week 24 prior to the third dose. The most common side effects related to vaccination were injection site pain, malaise, fatigue, muscle aches, and headaches.

“The viral titers after 3 doses were exceptionally high with over 80% achieving levels >1000 IU/ml,” Sherman said. “This is an important correlate of vaccine durability and was much higher than levels seen with other vaccine preparations.”

Based on the result, Sherman believes it’s likely that use of this vaccine product will be preferentially recommended in this treatment group. The preliminary findings were also shared with the Center for Disease Control Advisory Committee on Immunization Practices and the researchers await their recommendations.

The ACTG 5379 study will continue as planned to examine the effects of 2-dose HEPLISAV-B, as well as a 3-dose regimen of another hepatitis B vaccine (ENGERIX-B, manufactured by GSK) among adult participants with HIV who were previously vaccinated against HBV but who did not achieve an adequate immunologic response. The clinical trial is estimated to complete vaccinations in the spring of 2023.