Accelerated HBV vaccination schedule an option for HIV patients if CD4 cell count is high

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 1^st 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 HIV-positive patients.

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 schedule.

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 programme.

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 cell counts.

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 outcomes.

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.”