An accelerated hepatitis B vaccination schedule could be an
option for HIV-positive patients with a high CD4 cell count, Dutch research
published in the April 1st edition of the Journal of Infectious Diseases suggests.
Accelerated vaccination over a three-week period was shown
to be non-inferior for patients with a CD4 cell count above 500 cells/mm3
when compared to the standard six-month schedule.
Patients whose vaccination programme was accelerated were
significantly more likely to complete their schedule of vaccinaiton than the
patients whose immunisations were provide over the stand period.
However, accelerated vaccination was clearly inferior for
patients with lower CD4 cell counts.
“Its efficacy is only noninferior in patients with CD4 cell
count > 500 cells/mm3.
This finding supports the use of an accelerated HBV [hepatitis B virus]
vaccination schedule in HIV-infected patients with CD4 cell count above 500
cells/mm3,” comment the investigators.
Vaccination against hepatitis B is recommended for all
The vaccine is normally provided in three doses over a
six-month period (week 0; week 4; week 24). Not all HIV-positive patients
develop protective antibodies after receiving this immunisation, and response
had been tied to CD4 cell count and HIV viral load.
For the vaccination to have the best chance of success, it
is important that all three doses are received. However, poor adherence to the
vaccination schedule is common.
Studies in HIV-negative patients have suggested that an
accelerated programme of injections can improve adherence without compromising
the efficacy of the vaccine.
Dutch investigators wished to see if this was also the case
for patients with HIV. They therefore designed a randomised study involving 761
HIV-positive patients who were provided with an accelerated course of hepatitis
B vaccines (week 0; week 1; week 3), or the standard six-month treatment
The aim was to establish the non-inferiority of the
accelerated programme (10% difference in response). Responses to the vaccine
were assessed in both groups of patients after 28 weeks. The researchers also
wished to see if accelerated vaccination increased adherence to the vaccine
Overall, 38.7% of patients in the accelerated arm developed
protective antibodies against hepatitis B compared to 50% of individuals in the
standard dosing arm. This 11.3% difference did not meet the investigators
definition of non-inferiority.
However, they comment: “the difference is small and
compatible with the noninferiority margin, therefore, inferiority cannot be
concluded and the overall results are inconclusive.”
Outcomes were then compared according to the patients’ CD4
Accelerated vaccination was associated with a marginally
better response rate for patients with a CD4 cell count above 500 cells/mm3
(54% vs. 53% standard programme).
However, better outcomes were seen when the vaccine was
dosed over six months for patients with a CD4 cell count below 200 cells/mm3,
and for patients with a CD4 cell count between 201- 500 cells/mm3
(standard 27% vs. 13% accelerated; standard 54% vs. 34% accelerated).
Factors associated with a better response to vaccination
included a higher CD4 cell count, treatment with antiretroviral drugs, an
undetectable HIV viral load, and female sex (all < 0.001). In addition, HIV
therapy lasting four or more years was also associated with better vaccination
outcomes (p = 0.03).
In patients with a CD4 cell count above 500 cells/mm3,
use of HIV therapy, longer use of such treatment, an undetectable viral load,
younger age, and female sex were all associated with better vaccination
After taking these factors into consideration, accelerated
vaccination was still shown to be non-inferior for patients with higher CD4
cell counts (difference, 5%).
A total of 53 patients who received their injections over
three weeks had protective levels of anti-hepatitis B antibodies by week five,
and a further 24 individuals had a weak antibody response at this time.
The majority of responders (89%) still had protective
antibodies by week 28. In addition, 79% of partial responders had protection
against hepatitis B at this point, as did a quarter of patients who had not
responded by week five.
Adherence was significantly better in the accelerated arm
than the standard arm (92% vs. 83%, p < 0.001).
No serious adverse events were recorded. One patient
withdrew from the study because of an allergic reaction. Pain in the injection
site was the most commonly reported side-effect.
“In conclusion,” write the investigators, “patients with CD4
cell count > 500 cells/mm3 can be vaccinated against HBV can be
vaccinated according to an accelerated HBV schedule. Because compliance is significantly better in the accelerated
vaccination arm, this schedule is preferable.”