Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose
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
References (40)
- et al.
Hepatitis B and C in HIV-infected patients prevalence and prognostic value
J Hepatol
(1997) - et al.
Impaired response to hepatitis B vaccine in HIV infected children
Vaccine
(1992) - et al.
Hepatitis B vaccnation in infants of mothers infected with human immunodeficiency virus
J Pediatr
(1994) - et al.
Hepatitis B vaccination in prisons: the Catalonian experience
Vaccine
(1993) - et al.
Increasing the number of hepatitis B vaccine injections augments anti-HBS response rate in HIV-infected patients. Effects on HIV-1 viral load
Vaccine
(2000) - et al.
Immunology memory induced by hepatitis B vaccine
Vaccine
(1996) - et al.
Booster immunization of low-and non-responder after a standard three doses hepatitis B vaccine schedule—results of a post-marketing surveillance
Vaccine
(1997) - et al.
Prevalence of hepatitis B and C in the sera of patients with HIV infection in São Paulo
Brazil Rev Inst Med Trop S Paulo
(2000) - et al.
Prevalence of serologic markers of HBV and HCV infection in HIV-1 seropositive patients in Florianópolis Brazil
BJID
(1999) - et al.
Séroprévalence des marqueurs des virus des hépatites B C et D chez 500 patients infectés par le virus de l’immunodéficience humaine
Pathol Biol
(1997)
Hepatitis B in patients with HIV infection: relationship to AIDS and patient survival
Ann Intern Med
Prevalence of HVB HDV and HCV hepatitis markers in HIV-positive patients
Eur J Epidemiol
HBV, HDV and HIV infections in 242 drug addicts: 2-year follow-up
Eur J Epidemiol
The influence of human immunodeficiency virus type 1 infection on the development of the hepatiits B virus carrier state
JID
Outcome of hepatitis B virus infection in homossexual men and its relation to prior human immunodeficiency virus infection
J Infect Dis
Coinfection and superinfection of hepatitis B virus in patient infected with human immunodeficiency virus: no evidence of faster progression to AIDS
Scand J Infect Dis
Interations between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection
AIDS
The influence of HTLV-III infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers
Hepatology
Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men
Hepatology
Clinical aspects of interations between human immunodeficiency virus and the hepatotropic viruses
CID
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