Pneumococcal polysaccharide vaccine (PPV-23) has been recommended for HIV-infected adults. We investigated factors that could influence PPV-23 effectiveness against all-cause pneumonia in a longitudinal cohort of 23,255 HIV-infected adults receiving care during 1998--2003. Patients who received PPV-23 had a lower rate of pneumonia (IRR = 0.8; 95% CI: 0.8-0.9) than patients who had never been vaccinated, independent of recent CD4 count, HIV viral load, antiretroviral therapy, and history of pneumonia. However, PPV-23 provided no benefit when patients were vaccinated at HIV viral load > 100,000 copies/ml, irrespective of CD4 count at vaccination. Receipt of PPV-23 was associated with lower incidence of all-cause pneumonia.
"By using the incidence of clinical disease, we found that the viral load at the time of PPV-23 immunization was the most significant predictor of PPV-23 failure to provide protection. This has been shown with other vaccines in HIV populations, in conjunction with CD4 cell count [18,21]. The effect of CD4 is more difficult to evaluate due to confounding use of antibiotic prophylaxis (usually including co-trimoxazole) against Pneumocystis Jirovecii pneumonia in patients with low CD4 counts. "
[Show abstract][Hide abstract] ABSTRACT: The increasing use of highly active antiretroviral therapy (HAART) and pneumococcal immunization along with shifting community exposures may have altered the burden of Streptococcus pneumoniae disease in HIV-infected persons. We describe the burden and risk factors for pneumococcal disease in the modern era of HIV care and evaluate the use of a 23-valent pneumococcal polysaccharide vaccine (PPV-23).
The incidence of invasive pneumococcal disease (IPD) between January 1st, 2000 and January 1st, 2010 in a regional HIV population in Southern Alberta, Canada was determined by linking comprehensive laboratory and hospital surveillance data. Clinical and epidemiologic data including risk factors for S. pneumoniae, history of pneumococcal immunization, serotypes of infections, and length of any hospitalizations for pneumococcal disease were evaluated with multivariate analysis. CD4 count and viral load at immunization were evaluated with a nested case-control analysis.
In 1946 HIV-patients with 11,099 person-years of follow up, there were 68 distinct episodes of pneumococcal disease occurring in 50 patients. Increased risk was seen if female, age >60, Aboriginal ethnicity, lower education, injection drug use, smoking, nadir CD4 <200/μL, chronic obstructive pulmonary disease, and hepatitis C. Overall, the incidence of IPD was 342/100,000 person-years and was reduced to 187/100,000 within three years of PPV-23 immunization (P < 0.01). Although 78% of patients received PPV-23, 74% of IPD episodes were caused by PPV-23 serotypes. In a case-control analysis, HIV viral load at immunization was significantly predictive of PPV-23 failure, while CD4 count was not. 80% of IPD cases required hospitalization: median length of stay was 7 days (range: 1-71); four patients died.
Despite universal access to intensive measures to prevent pneumococcal disease including the widespread use of HAART and PPV-23 immunization, the incidence of IPD remains high in HIV patients with its associated morbidity and mortality.
[Show abstract][Hide abstract] ABSTRACT: Emerging and re-emerging infectious diseases are increasing throughout the world and highly pathogenic influenza is among those that pose a significant threat to mankind. Pandemic outbreaks of influenza are caused by the emergence of a highly pathogenic and transmissible virus to which the human population is immunologically naïve. Ongoing outbreaks of highly pathogenic avian influenza of the H5N1 subtype are of particular concern because of the high mortality rate (>60%) and novel subtype. Vaccines are considered the most effective way to prevent the morbidity and mortality associated with pandemic influenza and therefore developing an H5N1 vaccine is a public health priority. One of the hurdles facing H5N1 vaccine development is the antigenic diversity of the subtype as evidenced by the identification of ten phylogenetic clades. To overcome the challenge of antigenic diversity, a centralized hemagglutinin was developed and termed computationally optimized broadly reactive antigen (COBRA). The COBRA HA sequence was based upon HA amino acid sequences from clade 2 H5N1 human infections and the expressed protein retained the ability to bind the receptor, as well as mediate particle fusion. COBRA virus-like particle (VLP) vaccines elicited broadly reactive receptor blocking antibodies in multiple animal species: mice, ferrets and non-human primates. The reactivity profile was broader than that elicited by primary isolate-based vaccines given in either monovalent or polyvalent formulations. Although all vaccinated animals were protected from severe disease and death from experimental infection with highly pathogenic H5N1 virus, animals receiving the COBRA vaccine had reduced peak virus replication and cleared the infection more rapidly. COBRA vaccines were shown to be superior to primary isolate-based vaccines with both a broader antibody profile and more efficient protective efficacy. The development of COBRA resulted in a novel antigen generation methodology that is applicable to both pandemic and seasonal influenza.
[Show abstract][Hide abstract] ABSTRACT: Long-term antibody responses to 23-valent pneumococcal polysaccharide vaccine (PPV) among HIV-infected patients receiving highly active antiretroviral therapy (HAART) are rarely investigated.
Antibody responses to three pneumococcal capsular polysaccharides [Pneumococcal polysaccharide (PPS) 14, 19F and 23F] were assessed among 169 HIV-infected patients who received HAART and 23-valent PPV. Patients were stratified into four groups according to CD4 count at vaccination: group 1, CD4<100 cells/microL (n=35); group 2, CD4 100-199 cells/microL (n=36); group 3, CD4 200-349 cells/microL (n=34); and group 4, CD4>or=350 cells/microL (n=64). The proportion of patients who achieved increases in antibody titres of twofold or greater from baseline values (responders) was compared among the four groups of patients for five consecutive years after vaccination.
The proportion of responders to the three serotypes was significantly lower among patients in group 1 compared with those in the other three groups during yearly follow-up. Much faster loss of antibody responses was observed in group 1, although the rate of decline varied with the serotypes studied in the four groups. Compared with the nonresponders, more responders had CD4 counts >100 cells/microL at vaccination and achieved better virological suppression throughout the 5-year period, while the absolute increases of CD4 cell counts after HAART were not statistically significantly different.
Despite continued increases in CD4 cell counts after HAART, the proportion of HIV-infected patients who maintained antibody responses to PPV declined significantly over the 5-year follow-up period, especially among those who had CD4 counts <100 cells/microL at vaccination and who failed to achieve virological suppression.
HIV Medicine 07/2009; 11(1):54-63. DOI:10.1111/j.1468-1293.2009.00744.x · 3.99 Impact Factor
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