High-dose HBV vaccine improves HIV patients’ long-term immune response

Recent findings show that HIV patients immunized with high-dose recombinant hepatitis B vaccine demonstrated improved immune responses at 42 months compared with those who received standard- or low-dose injections.

“Although guidelines recommend hepatitis B virus (HBV) vaccination in patients with [HIV-1] infection without evidence of previous HBV exposure, responses to standard HBV vaccination regimens remain suboptimal compared with responses in HIV-seronegative individuals,” the researchers wrote. “The low seroconversion rate after HBV vaccination in immunocompromised patients is further complicated by a rapid decrease in antibody titers for those who had a response. Further precision on the duration of response achieved with alternative HBV vaccination regimens is needed.”

Previous data from a 2013 study of Kenyan adults noted poor responses to recombinant HBV vaccine among HIV patients; however, revaccination was shown to improve the hepatitis B surface antigen (HBsAb) levels of nonresponders.

To investigate a more effective initial regimen, researchers enrolled French adults at 33 treatment centers to randomly receive one of three HBV recombinant vaccine series: three intramuscular injections of the standard dose (20 g) at 0, 4 and 24 weeks; four intramuscular injections of high-dose (40 g) vaccine at 0, 4, 8 and 24 weeks; or four intradermal injections of low-dose (4 g) vaccine at 0, 4, 8 and 24 weeks. All participants were diagnosed with HIV, demonstrated a CD4 count exceeding 200 cells/L and had no serologic indication of HBV exposure. Although the study’s primary outcome initially was the proportion of patients with hepatitis B surface antigen (HBsAb) levels of at least 10 mIU/mL at week 28, follow-up was extended to observe responses at 18, 30 and 42 months.

Of the 437 randomized patients, 426 received at least one dose of vaccine. Approximately two-thirds of these were men, and the average age was 42.9 years. As previously reported, nearly 75% of all participants demonstrated an immune response at week 28.

When the analysis was extended to 42 months, the researchers observed a continued response among 71% (95% CI, 64-79) of patients who received the increased dosage. This rate was significantly greater than those seen among participants who received the standard (41%; 95% CI, 33-49) or reduced (44%; 95% CI, 35-53) dosages. Similarly, there was a greater proportion of responders demonstrating HBsAb titers of 100 mIU/mL or greater in the increased-dosage group (P < .001). Overall duration, as defined as the length of time until 15% of a group demonstrated titers of less than 10 mIU/mL, also was greater among high-dose vaccine recipients (P = .003).

“Inducing protection against HBV infection is critical in patients with HIV-1, given the increased risk for HBV infection and the increased risk for liver-related morbidity and mortality,” the researchers wrote. “Our results indicate that alternative vaccination schedules can be useful to improve long-term immune response to hepatitis B surface antigen and should encourage other attempts of alternative schedules.” – by Dave Muoio

Disclosure: Launay reports being an inspector in vaccine studies sponsored by Glaxo-SmithKline; Merck, Sharp and Dohme; Novartis Foundation; Sanofi Pasteur; and Sanofi Pasteur-MSD as well as receiving travel support to attend scientific meetings from GlaxoSmithKline; MSD; Pfizer; Sanofi Pasteur; and Sanofi Pasteur-MSD. Please see the full study for a list of all other authors’ relevant financial disclosures.

Recent findings show that HIV patients immunized with high-dose recombinant hepatitis B vaccine demonstrated improved immune responses at 42 months compared with those who received standard- or low-dose injections.

“Although guidelines recommend hepatitis B virus (HBV) vaccination in patients with [HIV-1] infection without evidence of previous HBV exposure, responses to standard HBV vaccination regimens remain suboptimal compared with responses in HIV-seronegative individuals,” the researchers wrote. “The low seroconversion rate after HBV vaccination in immunocompromised patients is further complicated by a rapid decrease in antibody titers for those who had a response. Further precision on the duration of response achieved with alternative HBV vaccination regimens is needed.”

Previous data from a 2013 study of Kenyan adults noted poor responses to recombinant HBV vaccine among HIV patients; however, revaccination was shown to improve the hepatitis B surface antigen (HBsAb) levels of nonresponders.

To investigate a more effective initial regimen, researchers enrolled French adults at 33 treatment centers to randomly receive one of three HBV recombinant vaccine series: three intramuscular injections of the standard dose (20 g) at 0, 4 and 24 weeks; four intramuscular injections of high-dose (40 g) vaccine at 0, 4, 8 and 24 weeks; or four intradermal injections of low-dose (4 g) vaccine at 0, 4, 8 and 24 weeks. All participants were diagnosed with HIV, demonstrated a CD4 count exceeding 200 cells/L and had no serologic indication of HBV exposure. Although the study’s primary outcome initially was the proportion of patients with hepatitis B surface antigen (HBsAb) levels of at least 10 mIU/mL at week 28, follow-up was extended to observe responses at 18, 30 and 42 months.

Of the 437 randomized patients, 426 received at least one dose of vaccine. Approximately two-thirds of these were men, and the average age was 42.9 years. As previously reported, nearly 75% of all participants demonstrated an immune response at week 28.

When the analysis was extended to 42 months, the researchers observed a continued response among 71% (95% CI, 64-79) of patients who received the increased dosage. This rate was significantly greater than those seen among participants who received the standard (41%; 95% CI, 33-49) or reduced (44%; 95% CI, 35-53) dosages. Similarly, there was a greater proportion of responders demonstrating HBsAb titers of 100 mIU/mL or greater in the increased-dosage group (P < .001). Overall duration, as defined as the length of time until 15% of a group demonstrated titers of less than 10 mIU/mL, also was greater among high-dose vaccine recipients (P = .003).

“Inducing protection against HBV infection is critical in patients with HIV-1, given the increased risk for HBV infection and the increased risk for liver-related morbidity and mortality,” the researchers wrote. “Our results indicate that alternative vaccination schedules can be useful to improve long-term immune response to hepatitis B surface antigen and should encourage other attempts of alternative schedules.” – by Dave Muoio

Disclosure: Launay reports being an inspector in vaccine studies sponsored by Glaxo-SmithKline; Merck, Sharp and Dohme; Novartis Foundation; Sanofi Pasteur; and Sanofi Pasteur-MSD as well as receiving travel support to attend scientific meetings from GlaxoSmithKline; MSD; Pfizer; Sanofi Pasteur; and Sanofi Pasteur-MSD. Please see the full study for a list of all other authors’ relevant financial disclosures.