1-Year Longitudinal Follow-up Study of Serologic Responses to 7-valent Pneumococcal Conjugated Vaccination and Opsonophagocytic Activities for Streptococcus Pneumoniae Among Patients With Human Immunodeficiency Virus Infection

Background:

Patients with human immunodeficiency virus (HIV) infection have higher incidence and recurrence rates of pneumonia and bacteremia caused by Streptococcus pneumoniae compared with the persons without HIV infection. Before the introduction of highly active antiretroviral therapy (HAART), the rate of invasive pneumococcal bacteremia was 100-fold greater in HIV-infected patients compared to HIV-negative controls. Since the introduction of HAART in 1996, the incidences of several AIDS-related opportunistic infections have significantly declined. However, the incidence of invasive pneumococcal disease in HIV-infected patients who received HAART is still 35~60-fold higher than non-HIV infected adults. The pathogenesis of invasive pneumococcal disease may be related to decrease of IL-8 level. By multivariate analysis, the major risk factors for pneumococcal bacteremia in HIV-infected patients include age, close exposure to children, associated comorbidity, smoking, alcohol abuse, injecting drug use, prior hospitalization, and CD4 count lower than 100 cells/ul; and the protective factors include HAART use and pneumococcal vaccination.

The 23-valent pneumococcal polysaccharide vaccine (PPV) is recommended for HIV-infected adolescents and adults who have CD4 lymphocytes count >/= 200 cells/ul and is optional for persons with a CD4 lymphocytes count <200 cells/ul. Revaccination one time should also be considered if the initial vaccination was given when the CD4 count was <200 cells/ul and if the CD4 count has increased to >200 cells/ul as a result of HAART. In the following years, there were several studies which had demonstrated that 23-valent PPV vaccination was associated with decreased risk of invasive pneumococcal disease. However, HIV-infected patients who do not have HAART therapy have significantly lower magnitude of antibody responses to 23-valent PPV than those receiving HAART and HIV-uninfected persons, and antibodies titers among HIV-infected patients seem to be associated with CD4 count. In addition, though the rates of decline of mean antibody concentrations in HIV-infected patients and in non-HIV-infected individuals were similar during 5 years after vaccination, as a consequence of lower postvaccination antibody concentration in HIV-infected patients, most of the HIV-infected patients have antibody concentrations below protection level within 3 years after vaccination. The impaired immune response to PPV may be due to PPV is T-lymphocyte-independent type 2 antigens (TI-2 antigens) instead of T-lymphocyte-independent type 1 antigens (TI-1 antigens). The response to TI-2 antigens is dependent on the number and function of T lymphocytes for the induction of an antibody response. Once T-lymphocyte's function is impaired, subsequent antibody response is also compromised. Therefore, the long-lasting immunity of PPV seems limited in HIV-infected patients.

The US Food and Drug Administration approved a 7-valent conjugated pneumococcal vaccine (PCV) in 2000. It contains seven S. pneumoniae polysaccharides combined with a carrier protein which is non-toxic mutant diphtheria toxin. With this combination, it can induce a T-cell dependent immune response and memory T and B cells and enhances better secondary antibody response after contact with the pathogen or revaccination. Several studies have demonstrated that 7-valent PCV-primed patients have higher antibody responses that also induce better opsonophagocytic activity in old or immunocompromised patients such as chronic lymphocytic leukemia, liver transplantation, or allogeneic stem cell transplantation. In HIV-infected patients, the efficacy of 7-valent PCV is also associated with CD4 count but the antibody response and opsonophagocytic activity are still better than those induced by PPV vaccination. However, the 7-valent PCV vaccination schedule and the necessity of booster vaccination are still unknown. In addition, long-term immunity to 7-valent PCV and the correlation with CD4 count are also under investigation.

The goal of our study is to compare the quantitative and functional antibody responses to 1-dose 7-valent PCV and 2-doses 7-valent PCV in HIV-infected patients, and also to compare these responses in HIV-infected patients with different categories of CD4 counts.