GM-CSF Fails to Improve Immune Responses to Booster Hepatitis B Vaccination in HIV-Infected Individuals
TL;DR: In this article, the authors randomized 60 HIV-infected subjects to receive a booster dose of HBV vaccine with 250mcg GM-CSF as an adjuvant or booster vaccine alone.
Abstract: Background: Hepatitis B (HBV) vaccination is an important preventive intervention for HIV-infected population. Data regarding booster HBV vaccine for persons with low HBV surface antibody (sAb) titers after vaccination in this immunocompromised population is lacking. Methods: We randomized 60 HIV-infected subjects lacking HBV protection after completion of 3 doses of HBV vaccine to receive a booster dose of HBV vaccine with 250mcg GM-CSF as an adjuvant or booster vaccine alone. Results: GM-CSF was safe with expected side effects. However, only 35% of persons receiving GM-CSF developed protective sAb while 50% in vaccine only arm developed protection (P = 0.47). Overall, only 28% of subjects maintained protective sAb 1 year after vaccination. Conclusions: GM-CSF failed to improve responses to the booster HBV vaccination. Overall, response was poor with only 42% of persons responding at one month post-vaccination confirming booster vaccination with the current HBV vaccine has poor immunogenicity among HIV-infected persons. Further research is needed to develop optimal vaccination strategies in HIV-infected persons.
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TL;DR: To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches.
Abstract: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.
79 citations
TL;DR: Recent advances on the roles of various cytokines in different phases ofHBV infection and cytokine-related mechanisms for impaired viral control and liver damage during HBV infection are discussed, and experimental therapeutic applications of cytokines are focused on to gain a better understanding of this newly emerging aspect of disease pathogenesis.
Abstract: Hepatitis B virus (HBV) infection is a worldwide health problem, with approximately one third of populations have been infected, among which 3–5 % of adults and more than 90 % of children developed to chronic HBV infection. Host immune factors play essential roles in the outcome of HBV infection. Thus, ineffective immune response against HBV may result in persistent virus replications and liver necroinflammations, then lead to chronic HBV infection, liver cirrhosis, and even hepatocellular carcinoma. Cytokine balance was shown to be an important immune characteristic in the development and progression of hepatitis B, as well as in an effective antiviral immunity. Large numbers of cytokines are not only involved in the initiation and regulation of immune responses but also contributing directly or indirectly to the inhibition of virus replication. Besides, cytokines initiate downstream signaling pathway activities by binding to specific receptors expressed on the target cells and play important roles in the responses against viral infections and, therefore, might affect susceptibility to HBV and/or the natural course of the infection. Since cytokines are the primary causes of inflammation and mediates liver injury after HBV infection, we have discussed recent advances on the roles of various cytokines [including T helper type 1 cells (Th1), Th2, Th17, regulatory T cells (Treg)-related cytokines] in different phases of HBV infection and cytokine-related mechanisms for impaired viral control and liver damage during HBV infection. We then focus on experimental therapeutic applications of cytokines to gain a better understanding of this newly emerging aspect of disease pathogenesis.
72 citations
TL;DR: The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination.
Abstract: Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines.
71 citations
TL;DR: It is shown that reinforced 40µg intramuscular HBV vaccination schedules are now frequently recommended, either initially in people never vaccinated, or in the lack of an anamnestic response in other situations.
Abstract: HBV immunization is highly recommended in people infected with HIV. However, the classical schedule used in the general population has been shown to be insufficient in people living with HIV. This ...
40 citations
Cites background from "GM-CSF Fails to Improve Immune Resp..."
...Numerous studies, from retrospective studies to randomized control trials (RCT), have found a correlation between undetectable HIV RNA, a high CD4 cell count and higher vaccination success.(19,20,23,27,30,60,63,75,93-97,100) The HIV viral load even seems to be more important than the CD4 count [19, 21, 23,], even though a positive correlation between the CD4 cell count at the time of (re)vaccination and the response to vaccination was observed in many studies....
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TL;DR: The necessity, timing and method of booster vaccination in responders with decreased anti-HBs responses, and effective vaccination against S-mutant HBV, are issues requiring resolution in the global prevention of HBV infection.
Abstract: Hepatitis B virus (HBV) infection is still a serious worldwide problem, and vaccination is the most effective strategy for primary prevention of the infection. Although universal vaccination may be required for total eradication, several countries, including Japan, have not yet adopted universal vaccination programs. Some individuals are non-responders to HBV vaccine and several mechanisms responsible for their poor response have been proposed. To overcome non-response, third generation vaccines with pre-S proteins have been developed. These vaccines have shown better anti-HBs responses and may also be effective in preventing infection by HBV with S mutant. Improvement of vaccine efficacy by intradermal administration, or co-administration with cytokines or adjuvants, may also be effective in non-responders. The necessity, timing and method of booster vaccination in responders with decreased anti-HBs responses, and effective vaccination against S-mutant HBV, are issues requiring resolution in the global prevention of HBV infection.
39 citations
References
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2,895 citations
"GM-CSF Fails to Improve Immune Resp..." refers background in this paper
...Hepatitis B virus (HBV), the leading worldwide cause of chronic liver disease [1,2], shares routes of transmission with Human Immunodeficiency virus (HIV) as manifest by the 30-90% of HIV-infected patients having evidence of prior HBV infection and 10% with chronic infection [3]....
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TL;DR: This review addresses many aspects of HBV infection, including the role of the immune system in determining the outcome of clinical infection, recent developments in molecular studies of the virus, and new treatments capable of eradicating chronic infection.
Abstract: The hepatitis B virus (HBV), discovered in 1966, infects more than 350 million people worldwide.1 Hepatitis B is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma, accounting for 1 million deaths annually. Knowledge of the intricacies of viral infection and of the molecular biology of this fascinating virus has led to the successful development of a vaccine and to treatment sometimes capable of eradicating chronic infection. This review addresses many aspects of HBV infection, including the role of the immune system in determining the outcome of clinical infection, recent developments in molecular studies of the virus, and new . . .
2,818 citations
TL;DR: The most recent version of the guidelines for the prevention and treatment of opportunistic infections (OI) in HIV-infected adults and adolescents was published in 2002 and 2004, respectively as mentioned in this paper.
Abstract: This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.
1,534 citations
Journal Article•
TL;DR: This report, the second of a two-part statement from the Advisory Committee on Immunization Practices (ACIP), provides updated recommendations to increase hepatitis B vaccination of adults at risk for HBV infection.
Abstract: Hepatitis B vaccination is the most effective measure to prevent hepatitis B virus (HBV) infection and its consequences, including cirrhosis of the liver, liver cancer, liver failure, and death. In adults, ongoing HBV transmission occurs primarily among unvaccinated persons with behavioral risks for HBV transmission (e.g., heterosexuals with multiple sex partners, injection-drug users [IDUs], and men who have sex with men [MSM]) and among household contacts and sex partners of persons with chronic HBV infection. This report, the second of a two-part statement from the Advisory Committee on Immunization Practices (ACIP), provides updated recommendations to increase hepatitis B vaccination of adults at risk for HBV infection. The first part of the ACIP statement, which provided recommendations for immunization of infants, children, and adolescents, was published previously (CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of infants, children, and adolescents. MMWR 2005;54[No. RR-16]:1-33). In settings in which a high proportion of adults have risks for HBV infection (e.g., sexually transmitted disease/human immunodeficiency virus testing and treatment facilities, drug-abuse treatment and prevention settings, health-care settings targeting services to IDUs, health-care settings targeting services to MSM, and correctional facilities), ACIP recommends universal hepatitis B vaccination for all unvaccinated adults. In other primary care and specialty medical settings in which adults at risk for HBV infection receive care, health-care providers should inform all patients about the health benefits of vaccination, including risks for HBV infection and persons for whom vaccination is recommended, and vaccinate adults who report risks for HBV infection and any adults requesting protection from HBV infection. To promote vaccination in all settings, health-care providers should implement standing orders to identify adults recommended for hepatitis B vaccination and administer vaccination as part of routine clinical services, not require acknowledgment of an HBV infection risk factor for adults to receive vaccine, and use available reimbursement mechanisms to remove financial barriers to hepatitis B vaccination.
1,146 citations
"GM-CSF Fails to Improve Immune Resp..." refers background in this paper
...Current guidelines recommend HBV vaccination for all HIV-infected persons who do not have evidence of current or past exposure to HBV [9,10]....
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TL;DR: Individuals coinfected with HIV-1 and HBV, especially those with low CD4+ nadir counts, are at increased risk for liver-related mortality, underscoring the importance of prevention, identification, and comprehensive management of hepatitis B in people infected withAIDS.
1,056 citations