愛滋病毒感染病患肺炎雙球菌疫苗接種後抗體效價反應之前瞻性研究: 著重在使用抗愛滋病毒藥物使用後之影響
Other Title
A Prospective Study of Anti-capsular Antibody Responses to Pneumococcal
Vaccination among HIV-infected Persons: Emphasis on Impact of Highly Active
Anti-Retroviral Therapy
Vaccination among HIV-infected Persons: Emphasis on Impact of Highly Active
Anti-Retroviral Therapy
Date Issued
2005
Date
2005
Author(s)
洪健清
DOI
932314B002086
Abstract
A 4-year prospective longitudinal follow-up study was conducted to assess the
immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV) among
305 HIV-1 infected individuals who received PPV and HAART between June 2000
and June 2004. 89 randomly selected vaccinees were stratified into 3 groups based on
their CD4 counts at baseline: Group 1 with CD4 counts less than 100 cells/µl; Group
2 with CD4 counts between 100 and 350 cells/µl; and Group 3 with CD4 counts
higher than 350 cells/µl. Antibody responses to 3 capsular antigens (14, 19F, and 23F)
were performed using home-made ELISA. Changes in these parameters from baseline
to week 4, and every 6 months thereafter were determined and compared using
Student’s t-test. Rates of response to vaccination in different groups of vaccinees were
compared using χ2 test. Vaccinees with more than 2-fold increase in antibody
responses were defined as vaccine responders. We found that immunization did not
cause any significant changes in CD4 counts or plasma HIV-RNA load between
vaccinees of different groups. For type 14, both the percentage of responders (27% v.s.
57% v.s. 54%) and the geometric mean fold-rise of reactive antibody (1.38 v.s. 2.89
v.s. 3.05) were significantly lower for Group 1 compared with Groups 2 and 3. The
duration of antibody responses in responders was similar between groups. Among the
24 responders who had been followed for more than 3 years, more than 75% of them
remained seropositive for type 14 irrespective of their baseline CD4 counts. Our
findings suggest that antibody responses to 23-valent PPV are poorer in HIV-infected
vaccinees with baseline CD4 counts less than 100 cells/µl compared with those with
baseline CD4 counts higher than 100 cells/µl. The responses may last for more than 3
years in 75% of the vaccine responders who continue to receive HAART regardless of
baseline CD4 + counts.
Patients with HIV infection are at higher risk for invasive infections due to
Streptococcus pneumoniae as compared with those without HIV infection. Rates of
invasive pneumococcal infections among AIDS patients may be as high as 100-fold
greater than in HIV-seronegative controls [1]. In the era of increasing rates of
antimicrobial resistance among isolates of S. pneumoniae worldwide as well as an
increased risk for developing invasive pneumococcal infections among HIV-infected
patients, the US Centers for Disease Control and Prevention (CDC) has strongly
recommended that pneumococcal vaccination be given to patients with HIV infection
who are aged ≥2 years [2] and a CD4+ count ≥200 cells/µl [3]. In addition,
revaccination is recommended when the CD4+ count increases to ≥200 cells/µl in
patients with an initial CD4+ count of <200 cells/µl [3].
However, these recommendations are notwithstanding, clinical studies evaluating
the benefits of pneumococcal vaccination among HIV-infected patients have yielded inconsistent results [4-7]. This inconsistency may be due to variations in the study
populations or designs, the receipt of antimicrobial prophylaxis or antiretroviral
therapy, or study end points and outcome measures. In retrospective studies conducted
in the US [4,6,7], vaccination reduced the risk for invasive pneumococcal infections
among HIV-infected patients before or after the introduction of highly active
antiretroviral therapy (HAART). In Uganda where HIV-infected patients had no
access to antiretroviral therapy (ART) [5], immunization with the 23-valent capsular
polysaccharide pneumococcal vaccine (PPV) paradoxically increased the incidence of
invasive pneumococcal infections and all-cause pneumonia. The reasons for such
failure of pneumococcal vaccination to confer protection against invasive
pneumococcal infections in Ugandan subjects remains unclear, although destruction
of B-cell function resulting from polysaccharide vaccination in those patients without
HAART or an increase of plasma HIV load has been proposed [5]. There remain
several potential explanations for the failure of the immunity of HIV-infected patients
to protect them from pneumococcal infections, including decreased serum opsonic
activity against S. pneumoniae in HIV-infected patients [8], and a local effect of
altered pulmonary immunoglobulin responses to penumococcal infection [9].
In the previous study [10], we have evaluated the impact of vaccination with the
23-valent PPV on HIV-infected patients who were receiving HAART. Our data
suggested that vaccination with 23-valent PPV reduced risks for pneumococcal
diseases and was associated with a lower risk for death among HIV-1-infected
patients receiving HAART. Vaccination did not increase the risks of all-cause
community-acquired pneumonia and HIV progression, and CD4+ continued to
increase and PVL decrease among HIV-infected patients receiving HAART. Despite
the clinical benefits, the serologic responses to the 23-valent PPV has rarely been
studied among HIV-infected patients receiving HAART; whether antibody responses
increase with immune reconstitution and when the booster vaccination should be
administered in HIV-infected patients receiving HAART remain to be studied. In this
study, we aim to evaluate the serial changes of anti-capsular antibodies in
HIV-infected patients who underwent vaccination with 23-valent PPV and received
HAART with increase of CD4+ counts.
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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