Vaccination significantly reduced the risk of pneumococcal pneumonia in HIV-positive patients in the US Veterans Aging Cohort 5-Site Study, according to results published in the April 1st edition of Clinical Infectious Diseases.
Even with the widespread use of antiretroviral therapy, pneumococcal pneumonia continues to be more common among HIV-positive than HIV-negative individuals – particularly those of black race.
While vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) is routinely recommended for those at risk, studies have not shown whether it is clearly effective at protecting against pneumonia.
Retrospective North American studies have shown a protective benefit in those with higher CD4 cell counts, while a recent Ugandan study (and the only prospective study of this clinical question to date) actually found that vaccination increased the short-term risk of pneumococcal pneumonia.
The Veterans Aging Cohort 5-Site Study (VACS 5) is an ongoing, prospective cohort study of HIV-positive patients, enrolled at several major US centres during 2001-2002, and HIV-negative controls matched by age, ethnicity and location.
For this analysis, patient records were retrospectively reviewed for PPV vaccination and diagnoses of pneumonia. Specific nonpneumococcal diagnoses (Pneumocystis carinii pneumonia, Haemophilus influenza pneumonia, pulmonary tuberculosis) were excluded; specific pneumococcal disease or pneumonia due to unspecified causes were considered (this broad definition was chosen since "in clinical practice, an etiologic diagnosis… is rarely made"). Patients were considered vaccinated if they had a record of PPV vaccination within three years prior to, or two years after, entering the study.
A total of 1626 patients – 934 HIV-positive and 692 HIV-negative – were included in the analysis. All were male; the HIV-positive participants were younger (49.2 vs. 55.4 years; p < 0.01) and included more African Americans (55% vs. 44%; p < 0.01), smokers (44% vs. 34%; p < 0.01), and people with alcohol or drug dependence (24% vs. 17% and 30% vs. 15%, respectively; p < 0.01 for both). Most (70%) of the HIV-positive patients were on antiretroviral therapy.
Vaccination had been received by 59% overall, with HIV-positive patients more likely to have been vaccinated than HIV-negative (69% vs. 46%; p < 0.01). Vaccinated patients were older (52.7 vs. 50.4 years; p < 0.05) and had more health conditions overall (1.7 vs. 1.3; p < 0.01), including drug disorders (25% vs. 21%; p < 0.05), coronary artery disease and/or congestive heart failure (12% vs. 8%; p < 0.05), diabetes (22% vs. 12%; p < 0.01), and cancer (18% vs. 13%; p < 0.01). There were no differences in ethnicity, smoking, alcohol use, or hemoglobin level between vaccinated and unvaccinated patients.
The observation period included the two years after vaccination or after study enrollement for vaccinated and unvaccinated patients, respectively. During this time, there were 97 incidents of pneumonia (6% of patients). (Pneumococcal-specific diagnoses were recorded for 14%; the remainder were nonspecific.)
During the observation period, HIV-positive patients were much more likely to have experienced pneumonia (9.1% vs. 1.7% in HIV-negatives; p < 0.01: hazard ratio [HR], 5.81; 95% confidence interval [CI], 3.15-10.71). PPV vaccination did not reduce the risk of pneumonia in HIV-negative patients or in the patient group overall. However, after controlling for CD4 cell count and viral load, vaccination reduced the risk of pneumonia in HIV-positive patients by roughly one third (HR, 0.65; 95% CI, 0.42–1.00; p < 0.05).
In the HIV-positive patients, risk factors for pneumonia were smoking (HR, 1.62; 95% CI, 1.03–2.55; p < 0.05), lower haemoglobin level (13.4 g/dL vs. 14.1 g/dL; p < 0.01) and lower CD4 cell count (331 cells/mm3 vs. 426 cells/mm3; p < 0.01).
The protective effect of PPV vaccination was seen despite the fact that, compared to the general HIV-positive US population, the HIV-positive group of the VACS 5 cohort is older and has higher proportions of African Americans, smokers, and people with comorbidities, all of which are risk factors for pneumococcal disease. In contrast with the Ugandan study, no increase in pneumonia incidence was seen in those vaccinated. Smoking and lower CD4 cell counts as risk factors are consistent with prior studies.
The researchers note that the lack of protection seen in the HIV-negative group may be due to study limitations and does not necessarily demonstrate a lack of efficacy in this group. The study observation period also needs to be considered with caution; for half of the vaccinated participants, the dates of vaccination and study entry were greater than a year apart, and patients who were vaccinated more than three years prior to study entry would have been classified as unvaccinated (which would, however, have tended to reduce the apparent benefit of vaccination).
In summary, the researchers conclude that "among HIV-infected patients, PPV vaccination offered protection against pneumonia events… support[ing] the current recommendation of vaccination of HIV-infected patients." The results also provide further justification to encourage smoking cessation strategies in HIV-positive individuals.
Rodriguez-Barradas MC et al. Impact of pneumococcal vaccination on the incidence of pneumonia by HIV infection status among patients enrolled in the Veterans Aging Cohort 5-Site Study. Clin Infect Dis 46: 1093-1100, 2008.