Immunological efficacy of a three-dose schedule of hepatitis A vaccine in HIV-infected adults: HEPAVAC study
The immunogenicity of vaccines, including vaccine against hepatitis A virus (HAV), is impaired in patients with HIV infection, requiring revised immunization regimens.
We evaluated the immunological efficacy and safety of a 3-dose schedule of hepatitis A vaccine in HIV-infected adults. HAV-seronegative HIV-infected adults were randomized to receive either 3 doses of 1440 UI of hepatitis A vaccine (HAVRIX; GlaxoSmithKline, Marly le Roi, France) at weeks 0, 4, and 24 (46 patients) or 2 doses 24 weeks apart (49 patients).
At week 28, seroconversion, defined as an anti-HAV antibody >or=20 mIU/mL, occurred in 82.6% and 69.4% of patients in the 3-dose and the 2-dose group, respectively (P = 0.13, intent-to-treat analysis, missing data = nonresponder), and in 88.4% and 72.3% of patients in the 3-dose and the 2-dose group, respectively (P = 0.06, observed analysis). Only 37.9% of patients experienced seroconversion after 1 vaccine dose (intent-to-treat analysis). Anti-HAV antibody geometric mean titers were 323 and 132 mIU/mL in the 3-dose group and 138 and 67 mIU/mL in the 2-dose group, respectively, 28 (P = 0.03) and 72 weeks (P = 0.05) after the first vaccine dose. There were no serious adverse events associated with the vaccine. Multivariate analysis showed no treatment group effect but indicated that absence of tobacco smoking (odds ratio = 2.92, 95% confidence interval: 1.07 to 7.97; P = 0.04) was an independent predictor of response to HAV vaccine.
In HIV-infected adults, immunogenicity of hepatitis A vaccine is poor. Three doses of vaccine were safe and increased antibody titers.
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Available from: Sharon Nachman
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ABSTRACT: HIV-infected individuals mount poor antibody responses to vaccines. We sought to identify the immunologic and virologic factors associated with a robust response to hepatitis A virus (HAV) vaccine in children on highly active antiretroviral treatment.
One hundred fifty-two pediatric highly active antiretroviral treatment recipients immunized against HAV at weeks 0 and 24 had anti-HAV antibodies, CD4+, CD8+, and CD19+ cell percent assessed at weeks 0 and 32. Subgroups had HIV viremia, B- and T-cell subpopulations, and cell-mediated immunity (CMI) to HAV and other stimulants measured.
Anti-HAV antibodies after complete vaccination correlated positively with CD4+ percent and CD19+ percent and negatively with viremia and CD8+ percent at baseline, but not at 32 weeks. There were no significant correlations between anti-HAV antibodies and B- or T-cell-naïve, memory, or activated subpopulations or non-HAV CMI. Compared with children who remained HAV-CMI-negative, those who mounted HAV-CMI in response to vaccination had higher anti-HAV antibody titers and CD19+ CD21+ CD27+ memory B cell percent at 32 weeks, but no other differences.
In HIV-infected children on highly active antiretroviral treatment, control of viral replication and conserved or reconstituted CD19+ and CD4+ cell numbers and function determine a robust antibody response to anti-HAV primary immunization. Our data support a bidirectional B- and T-cell cooperation in the response to the HAV vaccine.
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ABSTRACT: This review summarizes recent literature addressing immunization in the setting of HIV infection, with a specific focus on emerging evidence that can guide the care of HIV-positive adults.
There are few controlled studies on the clinical efficacy and effectiveness of vaccination in HIV-infected adults receiving highly active antiretroviral therapy (HAART). Published data indicate that HAART restores vaccine immunogenicity, improving the rates and persistence of immune responses, while reducing the risk of vaccine-related adverse events. Despite effective HAART, responses remain often suboptimal relative to HIV-negative individuals, although they improve with larger and more frequent vaccine doses. New vaccines are undergoing trial with promising results, including novel formulations against hepatitis B. Studies are also under way to explore the role of human papilloma virus vaccines for the prevention of anal cancer.
Protecting HIV-positive patients against vaccine-preventable infections is important now that HAART has restored life expectancy and general well being, and increased the likelihood of HIV-infected patients engaging in exposure-prone activities related to travel, occupation or social interaction. A proactive approach for vaccinating HIV-positive patients also serves an important public health purpose, reducing the pool of susceptible individuals and contributing to the control of prevalent and re-emerging infections.
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