HBV vaccine, CD4 count and increasing response with double-dose

Simon Collins, HIV i-Base

Veiga and colleagues from Brazil reported response rate by CD4 count to hepatitis B vaccination in 55 HIV positive patients and 20 HIV negative controls, who had received 3 doses (0, 30 and 180 days) of recombinant DNA hepatitis B vaccine. [1]

The overall HBV vaccine seroconversion rate was 59% (32/55) for HIV positive group, and 100% the 20 controls. Response rate by CD4 count at the time of vaccination were 81%, 65% and 25% in patients with >500, 200-499 and <200 cells/mm3 respectively.

The median CD4 count at the time of vaccination among responders was 452 cell/mm3, significantly higher than in non-responders (359 cells/m3, 20%, p=0.03). Memory T CD4+ cells were also significantly (p=0.04) higher in responders (255 cells/mm3) than in non-responders (178 cells/mm3). In addition, viral load at the time of immunisation was significantly (p=0.03) higher in non-responders (3.63 log10) than in responders (2.86 log10). Seven HIV-1 positive patients experienced a significant viral load increase, transient in five cases.

Response to HBV vaccine by CD4 count at vaccination (anti-HBs>10 UI/L)

CD4 count (cells/mm3) Response rate
>500 81%
200-499 65%
<200 25%

However, a larger study from Overton and colleagues at the Washington University School of Medicine, did not find a link with vaccine response and CD4 count. [2]

Of 342 recipients of regular 3-dose HBV vaccination programme, 149 subjects had complete data for evaluation; 35.6% were male, with a mean age of 34.3 years and baseline CD4 counts 429 cells/mm3

In this cohort, only 18 patients (12.1%) developed protective HBsAb (>10m IU/mL).

Baseline characteristics and timing of vaccine administration were not statistically different among responders and non-responders. Factors associated with a protective antibody response included male gender (p=0.001), older age (p=0.002), and an HIV plasma RNA level < 400 copies/mL at time of vaccination (p<0.001). Neither the CD4 cell counts at time of vaccine nor preceding CD4 cell nadir was predictive of successful response.

A strategy to improve response rates was suggested in a study by Fonseca and colleagues from University Medical School of Sao Paulo. This group randomised 210 patients to use either standard (20 μg) or double dose (40 μg) (given at 0, 1, 6 months, IM) to see whether this would increase response rates. [3]

Response rate (anti-HBs >10m IU/mL) was 47% for the double dose and 34% for the standard dose. A logistic regression model, showed a statistically significant higher seroconversion rate with the double dose, a history of HIV heterosexual exposure, CD4 cell counts >= 350 and HIV viral load < 10,000 copies/mL.

This study concluded that the best current strategy for a HBV vaccine response in HIV patients would be to use a double dose as a primary series when the viral load is likely to be low and when there is likely to be an adequate immune response. This might be early in the course of infection or following successful HAART.

A second study from Brazil, reported response rate of 47% using the double-dose strategy, and that responders had significantly higher CD4 counts than non-responders. However the study abstract contained no further breakdown by CD4 levels. [4]


  1. Veiga APR, Casseb J, Duarte AJS – Efficacy to hepatitis B vaccination and its relationship with T CD45RA+ (naive) and CD45RO+ (memory) subsets in HIV-1-infected subjects. XV Intl AIDS Conference, Bangkok. Abstract B10392.
  2. Overton ET, Sungkanupargh S, Seyfried W et al. Protective immunity after hepatitis B vaccination in HIV-infected persons: Does an undetectable HIV RNA level predict success? XV Intl AIDS Conference, Bangkok. Abstract MoPeB3284.
  3. Fonseca MO, Pang LW, 2, Cavalheiro NP et al. Randomised trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose. XV Intl AIDS Conference, Bangkok. Abstract MoPeB3312.
  4. Conference Góngora DVN, Góngora-Rubio F, Onishi E et al. Serological responses to hepatitis B vaccination in HIV infected patients. XV Intl AIDS Conference, Bangkok. Abstract B10109.

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