Elsevier

Vaccine

Volume 23, Issue 22, 22 April 2005, Pages 2902-2908
Vaccine

Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose

https://doi.org/10.1016/j.vaccine.2004.11.057Get rights and content

Abstract

Because HIV and hepatitis B virus share many common risk factors, it is important to try to vaccinate HIV patients against hepatitis B. There are numerous reports describing a variety of dose schedules, limited success and markers associated with impaired response to HBV vaccine in these individuals. All studies have been small in size making it difficult to draw conclusions within and between studies. The purpose of this study was to evaluate a double dose of hepatitis B vaccine under more definitive guidelines: double blinded, randomized, controlled, with numbers for statistical validity. Two hundred and ten HIV infected subjects received a standard dose (20 μg) or a double dose (40 μg) of recombinant hepatitis B vaccine IM 0, 1 and 6 months. Ninety-four receiving standard dose and 98 receiving double dose completed the study. The seroconversion rate (anti-HBs  10 mIU/mL) was 47 and 34% for double dose and standard dose, respectively (p = 0.07). A statistically significant higher seroconversion rate was associated with double dose comparing with standard dose for patients with CD4 cell counts ≥350 cells/mm3 (64.3% × 39.3%; p = 0.008) but made no difference to seroconversion in those with CD4 <350 (23.8% × 26.3%; p = 0.80). Double dose also improved seroconversion comparing with standard dose for patients with HIV viral load <10,000 copies/mL (58.3% × 37.3%; p = 0.01) but made no difference to seroconversion in those with HIV viral load ≥10,000 copies/mL (16% × 17%; p = 0.7). Based on the results of this study, the best current strategy for hepatitis B vaccination in HIV patients would be to use a double dose as a primary series when the viral load is likely to be low and CD4  350, when there is likely to be an adequate immune response.

Introduction

The human immunodeficiency virus (HIV) and hepatitis B virus (HBV) share many similar risk factors and routes of transmission, resulting in a high prevalence of co-infection [1], [2], [3], [4], [5], [6], [7]. In addition, HIV infection is associated with a greater chance of chronic HBV carrier state [8], [9], [10], a higher level of HBV replication [11], [12], [13], [14], increasing its potential for transmission. Although there is a great need for HBV prevention in HIV infected patients, vaccine efficacy (as measured by seroconversion) has been poor, in HIV-infected children and adolescents [15], [16], [17], [18], [19], [20], [21], [22] as well as in adults [9], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33]. Currently, there are no data to determine the best HBV vaccine schedule for HIV-infected patients. The Advisory Committee on Immunization Practices (ACIP/CDCP) recommends that the anti-HBs response of HIV-infected patients should be measured post-vaccination, followed by one to three additional doses if antibody levels are low (≤10 mIU/mL). The immunogenicity of higher doses in a primary series is unknown, and recommendations cannot be made at this time [34]. Along similar lines, the European Consensus Group on Hepatitis B Immunity recommends double or additional doses of HBV vaccine for immunocompromised individuals who do not respond to standard schedules. There is an additional recommendation to administer the vaccine when patients’ immune responses are likely to be high [35]. On the other hand, the World Health Organization, considers the data too limited to recommend the administration of additional doses of HBV vaccine to HIV-infected children [36]. The Brazilian Ministry of Health recommends doubling the primary dose of HBV vaccination for immunocopromized patients including those with HIV.

The purpose of this project was to design a large, double blind, randomized, controlled study to compare seroconversion rates of a double dose to a standard dose of HBV vaccine in HIV infected adult patients. As part of this evaluation, risk factors (such as CD4 counts and HIV viral load) of low response rates would be examined. A secondary objective was to evaluate the influence of the vaccine on CD4 cell counts and HIV viral loads.

Section snippets

Study design and subjects

The project was approved by the Ethics Comission for Analysis of Research Projects (CAPPesq) of the University Medical School of Sao Paulo, Brazil. Patients positive for anti-HIV antibodies, greater than 18 years of age, negative for any HBV serological marker, without history of previous hepatitis B vaccine, without active opportunistic infection (at the time of admission) and willing to sign informed consent, were selected from HIV outpatient attending at University's clinic in Sao Paulo

Results

Two hundred and ten HIV-infected adults were enrolled into the trial. One hundred and ninety-two subjects (91%) completed the study, 94 in the standard dose group and 98 in the double dose group. The patients were recruited between November 2000 and May 2002, and followed untill January 2003. There was no difference between the two groups regarding: gender, age, body mass index (BMI), smoking and drinking habits, HIV exposure criteria, antiretroviral therapy use, previous opportunistic

Discussion

This study confirms previous reports that HIV-infected patients have a poor response to HBV vaccine and it is likely due to the immuno-supressive effects of HIV. Unlike previous studies with a preponderance of males and homosexuals, this study has a much higher proportion of females and heterosexuals. This difference reflects the current demographic trend in the HIV epidemic of Brazil. Regarding the dosing schedule of HBV vaccine, other studies in HIV infected children evaluated a similar

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