Hepatitis B vaccination consisting of four doses produces a better response in HIV-positive patients than the standard three-dose vaccination schedule, French investigators report in the April 13th edition of the Journal of the American Medical Association.
An especially good response to vaccine was observed in patients who received four intramuscular 40 μg injections (double the standard dose). Patients who received four 4 μg injections under the skin were also more likely to develop protective antibodies than individuals who received the standard three intramuscular injections of 20 μg of the vaccine.
Only one serious side-effect was possibly associated with the experimental vaccination schedules, but overall they appeared safe.
Hepatitis B is a major cause of liver disease in patients with HIV, and all HIV-positive individuals are recommended to be vaccinated against the infection.
Response rates to the vaccine vary between 18% and 72% in patients with HIV, much lower than the 90% rate observed in the general population.
Alternative vaccination schedules and doses are therefore being investigated as ways of improving response rates in patients with HIV.
Researchers in France designed a phase 3, open-label randomised study to investigate three different vaccination strategies.
Patients in the first arm of the study were received the standard 20 μg dose of the vaccine via intramuscular injection on three occasions (day 0, week 4, week 24).
Individuals in the second arm were treated with a 40 μg intramuscular dose on four occasions (week 0, week 4, week, 8, week 24).
The third arm of the study involved patients who were vaccinated using a 4 μg dose. This was administered by four injections under the skin (day 0, week 4, week 8, and week 24).
Antibody responses at week 28 were compared between the three groups of patients, and information was also gathered on safety.
A total of 437 patients were recruited to the study between June 2007 and October 2008. All had a CD4 cell count above 200 cells/mm3 and there were no significant differences between the three study arms.
Overall, a vaccination response was observed in 65% of patients. However, rates differed significantly between the three arms of the study.
Two-thirds of patients who received the standard three doses of the vaccine developed antibodies to hepatitis B. This compared to 86% of patients who received four intramuscular injections of the 40 μg dose (p < 0.001 vs. standard dosing), and 79% of individuals vaccinated with the 4 μg intradermal dose on four occasions (p = 0.02 vs. standard dosing).
A high-level antibody response was observed in 41% of patients in the first study arm, 74% of patients in the second arm (p < 0.01 vs. arm 1), and 44% of individuals in arm 3 (p = 0.06 vs. standard dosing).
At week 28, mean antibody titres were 55 miu/ml among patients who received the 20 μg dose on three occasions; 795 miu/ml for patients treated with the 40 μg intramuscular dose on four occasions (p < 0.001 vs. arm 1); and 104 miu/ml for patients in arm 3 of the study (p = 0.05 vs. arm 1).
Statistical analysis confirmed that both vaccination schedules involving four doses were associated with a better response compared to the standard schedule (40 μg = AOR, 3.58; 95% CI, 1.92-6.67; 4 μg = AOR, 2.09; 95% CI, 1.18-3.68).
Each 100 cell increase in baseline CD4 cell count was associated with a significant enhancement in response (AOR = 1.12; 95% CI, 1.00-1.26), and women were more likely to develop protective antibodies than men (AOR = 2.03; 95% CI, 1.11-3.73).
Smoking and a detectable viral load were both associated with poorer outcomes.
Overall, the vaccination schedules involving four doses appeared safe, and did not have an adverse impact on either CD4 cell count or viral load. The most commonly reported side-effects were fever, nausea or injection-site reaction.
However, one patient in the 40 μg arm developed severe cytolysis, which the investigators concluded was “possibly” related to the vaccine.
“In a large randomized controlled trial, both the 4 intramuscular double-dose regimen and the 4 intradermal low-dose regimen improved serological response in comparison with standard hepatitis B vaccine in adults with HIV infection with CD4 cell counts of more than 200 cells/μl,” conclude the investigators.
Launay O et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1. JAMA 305: 1432-40, 2011.