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Keywords:

  • HIV infection;
  • invasive pneumococcal disease;
  • pneumococcal pneumonia;
  • pneumococcal vaccine;
  • 23-valent polysaccharide vaccine

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Background

Recent studies in hospitalized patients with community-acquired pneumonia have found a lower risk of bacteraemia and better clinical outcomes in patients who had previously received the 23-valent pneumococcal polysaccharide vaccine (PPV) in comparison with unvaccinated individuals. The aim of this study was to assess the influence of prior PPV on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease (IPD).

Methods

This was an observational study of all consecutive HIV-infected adults hospitalized with IPD from January 1996 to October 2007 in three hospitals in Spain. Baseline characteristics and clinical outcome-related variables were compared according to prior PPV vaccination status.

Results

A total of 162 episodes of IPD were studied. In 23 of these (14.2%), patients had previously received PPV. In both vaccinated and unvaccinated patients, most of the causal serotypes were included in the 23-valent PPV (76.9% and 84.1%, respectively). Overall, 25 patients (15.4%) died during hospitalization, 21 patients (13%) required admission to an intensive care unit (ICU) and 34 patients (21%) reached the composite outcome of death and/or admission to the ICU. None of the 23 patients who had previously received PPV died or required ICU admission, in comparison with 25 (18%; P=0.026) and 21 (15.1%; P=0.046), respectively, of the unvaccinated patients. The length of hospital stay for vaccinated patients was significantly shorter (8.48 vs. 13.27 days; P=0.011).

Conclusions

Although 23-valent PPV failed to prevent IPD in some HIV-infected patients, vaccination produced beneficial effects on clinical outcomes by decreasing illness severity and mortality related to IPD.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Since the widespread introduction of highly active antiretroviral therapy (HAART), decreasing rates of invasive pneumococcal disease (IPD) in HIV-infected patients [1–7] have been reported. Despite these data, the incidence of IPD in persons with HIV infection remains significantly higher than in similarly aged non-HIV-infected adults [1,2,5]. Advanced immunodeficiency and the association with other comorbidities appear to be the main risk factors for IPD [6–11], but a high incidence of IPD has also been reported, even in HIV-infected patients with CD4 counts >200 cells/μL [2].

Studies assessing the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV) in preventing pneumococcal pneumonia and IPD in HIV-infected adults have yielded controversial results. Several cohort and case–control studies have found that the vaccine produces a beneficial effect by decreasing the incidence of IPD, particularly in patients receiving HAART and with higher CD4 counts but also in patients with CD4 counts below 200 cells/μL [4,6,7,12–14]. In contrast, other studies, including the only published randomized double-blind placebo-controlled study, have not found a clear benefit of the 23-valent PPV in preventing IPD in HIV-infected patients [10,15–18]. In any case, because the impact of pneumococcal infections on morbidity and mortality remains high, vaccination with 23-valent PPV is currently recommended in HIV-infected patients, particularly in those with CD4 counts >200 cells/μL [19,20].

Recent studies in hospitalized patients with community-acquired pneumonia (CAP) have found a lower risk of bacteraemia and better clinical outcomes, including a faster resolution of pneumonia symptoms, a shorter length of hospital stay and a lower mortality rate, in patients who had previously received the 23-valent PPV compared with unvaccinated individuals [21–23]. Furthermore, among patients with documented pneumococcal pneumonia and patients with major risk factors for pneumococcal pneumonia (i.e. older patients and nursing home residents) the association of prior vaccination with 23-valent PPV and better clinical outcomes appeared to be more significant [21]. To our knowledge there are no published data about these additional effects of 23-valent PPV in HIV-infected patients. The aim of the present study was to assess the influence of prior 23-valent PPV on clinical outcomes in HIV-infected adults hospitalized with IPD.

Patients and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Study population and setting

We performed an observational study of all consecutive HIV-infected adults (age ≥18 years) hospitalized with IPD from January 1996 to October 2007 in three hospitals in Spain: University Hospital Vall d'Hebron (a 1200-bed tertiary care teaching hospital that treats 1900 HIV-infected patients; Barcelona), Hospital Son Dureta (a 900-bed tertiary care teaching hospital that treats 2000 HIV-infected patients; Palma de Mallorca) and Hospital Mutua de Terrasa (a 580-bed secondary care teaching hospital that treats 400 HIV-infected patients; Barcelona). During the study period, 179 episodes of IPD were diagnosed in 165 HIV-infected hospitalized adults. Seventeen episodes were excluded because data on the patients' vaccination status were not available. Thus, 162 cases were finally included in the study. Fifteen patients had more than one episode of IPD: one patient had four episodes, three patients had three episodes and 11 patients had two episodes. Among this group of 15 patients with repeated episodes of IPD (overall 35 episodes), in six episodes the patient had received PPV prior to the pneumococcal infection episode and in 29 episodes the patient had not been previously vaccinated. Three patients received 23-valent PPV after the first episode of IPD. Because the different vaccination status of the same patient in different episodes of IPD could influence the outcomes, we decided to choose the overall number of episodes and not patients for the analysis. The study was approved by the Commission of Medical Ethics of the Vall d'Hebron Hospital where all data were centralized.

Study variables and data collection

The patients' records from 1996 to 1999 were reviewed retrospectively, and from 2000 onwards all data were collected prospectively. The following variables were recorded: (1) demographic and epidemiological data (age, gender, active or prior injecting drug use, current tobacco smoking and current alcohol abuse); (2) prior vaccination with 23-valent PPV; (3) clinical conditions associated with higher risk for pneumococcal disease (cirrhosis or chronic liver disease, chronic pulmonary disease, solid neoplasm, haematological malignancy and splenectomy); (4) HIV infection-related data (HIV infection risk factors, CD4 lymphocyte count, HIV-1 viral load, current use of HAART, current or prior AIDS-defining illnesses and trimethoprim-sulfamethoxazole prophylaxis); (5) clinical syndrome (pneumonia, meningitis, peritonitis and primary bacteraemia); (6) pneumonia severity assessed with the Pneumonia Severity Index (PSI) at the moment of admission to the Emergency Department; (7) microbiological data (serotype and antibiotic resistance pattern of the Streptococcus pneumoniae causal strain); and (8) variables related to clinical outcome [in-hospital mortality, intensive care unit (ICU) admission, orotracheal intubation requirement, time to defervescence and length of hospital stay].

Pneumococcal vaccination status

Baseline characteristics and variables related to clinical outcome were compared according to prior PPV vaccination status. In our setting, primary care physicians do not administer PPV to HIV-infected patients and the vaccines are all administered in the hospital in which these patients are managed. In our hospitals, all HIV-infected patients who receive the 23-valent PPV are recorded in a database by the Infectious Disease Department and/or the Preventive Medicine Department. Informed consent is obtained before the inclusion of the data in the database. Both databases were checked to ascertain the vaccination history of each patient. We considered that a patient was vaccinated if he or she had ever received the 23-valent PPV prior to the IPD episode.

Definitions

IPD was defined as isolation of S. pneumoniae from a normally sterile site (blood, cerebrospinal fluid, pleural fluid or peritoneal fluid). Invasive pneumococcal pneumonia was diagnosed when a patient had consistent clinical findings plus a new pulmonary infiltrate on chest radiography and isolation of S. pneumoniae in blood and/or pleural fluid cultures. HAART was defined as the use of an antiretroviral agent combination based on current guidelines for HIV infection management. Chronic liver disease was defined on the basis of the presence of typical clinical, laboratory and/or ultrasonography signs and/or the presence of histological findings in liver biopsy. Chronic obstructive pulmonary disease (COPD) was defined on the basis of clinical and/or functional test-based criteria. Pneumococcal serotypes related to those serotypes contained in the 23-valent PPV were not considered as vaccinal serotypes, because cross-immunity between related serotypes has not been demonstrated [24]. ‘Days to defervescence’ was the number of days from admission to the disappearance of fever. In-hospital mortality was defined as deaths that occurred during the hospital stay for IPD.

Microbiological procedures

S. pneumoniae strains were identified by Gram staining, optoquin susceptibility, bile solubility testing and latex agglutination testing. The antibiotic susceptibility was assessed, according to current Clinical and Laboratory Standards Institute (CLSI) recommendations, using Mueller–Hinton agar supplemented with 5% horse blood (Kirby Bauer diffusion method) and Rosco disks (neo-Sensifab; Rosco Diagnostica, Tastrup, Denmark). Minimum inhibitory concentrations (MICs) of penicillin G, cefotaxime and cotrimoxazole were determined by Etest (bioMérieux SA, Marcy l'Etoile, France) Isolates were classified as penicillin-susceptible (MIC ≤0.06 mg/L), penicillin-intermediate (MIC 0.12–1 mg/L), or penicillin-resistant (MIC ≥2 mg/L). Intermediate or resistant isolates were considered to be nonsusceptible. All microbiological tests except for serotyping were performed with the same methods at each hospital. Isolates were serotyped at the Spanish Pneumococcal Reference Laboratory (Instituto de Salud Carlos III, Madrid, Spain) with standard antiserum. The serotype identification was only performed on patients admitted to two of the three hospitals, so only data from 101 cases were available.

Outcome-related variables

The main measured outcomes were in-hospital mortality and ICU admission. In previous studies a composite of the two variables was used to assess the severity of CAP, so we decided to choose the composite variable ‘mortality and/or ICU admission’ as our primary outcome [22,25]. Secondary outcomes were: in-hospital mortality alone, ICU admission, orotracheal intubation requirement, severity of pneumonia at presentation (PSI class IV or V), development of septic shock or empyema, length of hospital stay and time to defervescence.

Statistical analysis

All variables were compared according to the prior vaccination status of the patients in each episode of IPD analysed (patients who had been vaccinated with the 23-valent PPV and unvaccinated patients). Statistical analyses were performed using the statistical software package spss version 12.0 (SPSS, Chicago, IL, USA). Categorical variables were compared using the χ2 test or Fisher's exact test and continuous variables using Student's t-test. Differences were considered significant at P<0.05.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

A total of 162 episodes of IPD were studied. The mean age of patients was 38.5 years, and 126 (77.8%) episodes occurred in men and 36 (22.2%) in women. In 23 episodes (14.2%), the patient had previously received the 23-valent PPV, and in seven episodes the vaccine was administered more than 5 years before the episode of IPD.

Baseline characteristics of the patients stratified by 23-valent PPV vaccination status are shown in Table 1. There were some differences between vaccinated and unvaccinated patients at baseline. There was only one patient (4.3%) with chronic liver disease among the vaccinated patients, in comparison with 27 (19.4%) of 139 unvaccinated patients, although the difference was not significant. Prior vaccine recipients had significantly higher CD4 counts at the time of pneumococcal infection (325 cells/μL in vaccinated patients vs. 209 cells/μL in unvaccinated patients; P=0.014) and were more likely to be on HAART (59.1%vs. 34.5%; P=0.034).

Table 1.   Baseline characteristics of patients according to pneumococcal vaccination status
 Vaccinated patients (n=23)Unvaccinated patients (n=139)P
  1. *Hospitalization in the previous 3 months.

  2. COPD, chronic obstructive pulmonary disease; HAART, highly active antiretroviral therapy; SD, standard deviation; TMP-SMZ, trimethoprim-sulfamethoxazole.

Age (years) [mean (SD)]38.5 (9.1)38.5 (8.6)0.993
Sex [n (%)]
 Male20/23 (87)106/139 (76.3)0.416
 Female3/23 (13)33/139 (23.7) 
Tobacco use [n (%)]17/23 (73.9)90/138 (65.2)0.482
Alcohol abuse [n (%)]4/23 (17.4)31/138 (22.5)0.786
Chronic liver disease [n (%)]1/23 (4.3)27/139 (19.4)0.132
COPD [n (%)]2/23 (8.7)9/139 (6.5)0.657
Haematological malignancy and/or splenectomy [n (%)]4/23 (17.4)4/139 (2.9)0.015
Solid neoplasm [n (%)]0/232/139 (1.4)1
Prior hospitalization* [n (%)]4/23 (17.4)40/138 (29)0.318
Current or previous injecting drug use [n (%)]13/23 (56.5)103/139 (74.1)0.132
CD4 lymphocyte count [mean (SD)]325 (244.2)209 (192.1)0.014
CD4 ≥200 cells/μL [n (%)]15/21 (71.4)61/138 (44.2)0.033
HIV-1 viral load <50 copies/mL [n (%)]5/20 (25)13/113 (11.5)0.148
HAART use [n (%)]13/22 (59.1)48/139 (34.5)0.034
Prophylactic TMP-SMZ [n (%)]5/22 (22.7)40/138 (29)0.619
Previous AIDS-defining illness [n (%)]9/23 (39.1)58/138 (42)0.824

The most common clinical presentation of IPD was bacteraemic pneumonia in both groups of patients and, interestingly, none of the patients who had received the 23-valent PPV had meningitis (Table 2). We could determine pneumococcal serotype in 101 cases. In 84 of them (83.2%) the serotype of the pneumococcal strain was included in the 23-valent PPV without significant differences between vaccinated and unvaccinated patients (76.9%vs. 84.1%).

Table 2.   Clinical and microbiological characteristics according to pneumococcal vaccination status
 All patients (n=162; 100%)Vaccinated patients (n=23; 14.4%)Unvaccinated patients (n=139; 85.6%)P
  • Values shown are number/total tested (%).

  • *

    Proportion among patients for whom data were available.

  • PPV, pneumococcal polysaccharide vaccine.

Bacteraemic pneumonia134/162 (82.7%)21/23 (91.3%)113/139 (81.3%)0.376
Primary bacteraemia8/162 (4.9%)2/23 (8.7%)6/139 (4.3%)0.317
Meningitis10/162 (6.2%)0/2310/139 (7.2%)0.360
Peritonitis10/162 (6.2%)0/2310/139 (7.2%)0.360
23-valent PPV included serotype*84/101 (83.2%)10/13 (76.9%)74/88 (84.1%)0.455
Penicillin nonsusceptible strain*60/157 (38.2%)5/23 (21.7%)58/139 (41.7%)0.104
Cefotaxime nonsusceptible strain*22/128 (17.2%)1/20 (5%)21/108 (19.4%)0.194
Cotrimoxazole nonsusceptible strain*68/153 (44.4%)5/20 (25%)63/133 (47.4%)0.090

In Table 3 we show the outcome variables related to pneumococcal infection according to prior pneumococcal vaccination. Overall, in 21 episodes (13%) patients required ICU admission, 25 patients (15.4%) died during their hospital stay, and in 34 episodes (21%) patients reached the composite outcome of death and/or admission to the ICU. In none of the 23 episodes that occurred in patients who had previously received the 23-valent PPV was the composite outcome of death and/or admission to the ICU reached, in comparison with 34 episodes (24.5%) that occurred in unvaccinated patients (P=0.004). None of the vaccinated patients died or required ICU admission, in contrast with 25 (P=0.026) and 21 (P=0.046) of the unvaccinated patients, respectively. Moreover, the mean length of hospital stay was significantly shorter in vaccinated patients (8.48 vs. 13.27 days; P=0.011). When we examined the subgroup of patients with bacteraemic pneumonia, we found that those who had received the 23-valent PPV were less likely to have severe pneumonia at clinical presentation (PSI class IV or V) than unvaccinated patients (16.7 and 37.4%, respectively) and none of the vaccinated patients developed empyema compared with 9.3% of the unvaccinated patients, although these differences were not significant.

Table 3.   Outcome variables related to invasive pneumococcal disease according to prior vaccination status; on the right side of the table, patients with chronic liver disease have been excluded
(n=162)All patients (n=162)All patients includedPatients with chronic liver disease excluded*
Vaccinated (n=23)Unvaccinated (n=139)PVaccinated (n=22)Unvaccinated (n=112)P
  • Values shown are number/total tested (%), unless otherwise stated.

  • *

    28 patients with chronic liver disease were excluded.

  • Pneumonia Severity Index (PSI) class IV or V. PSI was available for 125 patients with bacteraemic pneumococcal pneumonia.

  • ICU, intensive care unit; SD, standard deviation.

Death and/or ICU admission34/162 (21)0/2334/139 (24.5)0.0040/2225/112 (22.3)0.013
In-hospital mortality25/162 (15.4)0/2325/139 (18)0.0260/2216/112 (14.3)0.073
ICU admission21/162 (13)0/2321/139 (15.1)0.0460/2219/112 (17)0.042
Orotracheal intubation15/162 (9.3)0/2315/139 (10.8)0.1320/2213/112 (11.6)0.126
Shock17/135 (12.6)1/21 (4.8)16/114 (14)0.4711/20 (5)14/96 (14.6)0.463
Empyema10/129 (7.8)0/2110/108 (9.3)0.3650/2010/95 (10.5)0.206
PSI high risk classes43/125 (34.4)3/18 (16.7)40/107 (37.4)0.1112/17 (11.8)29/95 (30.5)0.146
Days of hospital stay [mean (SD)]12.62 (13.87)8.48 (6.14)13.27 (14.62)0.0118.5 (6.29)14.29 (15.88)0.007
Days to defervescence [mean (SD)]3.11 (4.09)2.55 (2.72)3.21 (4.28)0.4842.62 (2.76)3.17 (3.52)0.497

Only one of the 24 patients with chronic liver disease had received 23-valent PPV. As chronic liver disease has been described as a risk factor for pneumococcal infection and this condition could influence the results, favouring a worse prognosis in unvaccinated patients, we attempted to avoid a possible selection bias by performing a new analysis excluding all patients with chronic liver disease (Table 3). In this subgroup of patients the difference between vaccinated and unvaccinated patients remained significant when the composite outcome of death or admission to the ICU was measured. None of the previously vaccinated patients reached this composite outcome, in contrast with 22.3% of the unvaccinated patients (P=0.013). The proportion of unvaccinated patients who died during their hospital stay (14.3%) or required ICU admission (17%) remained higher than that for vaccinated patients, where there were no deaths or ICU admissions, although differences in mortality rates were not statistically significant. The length of hospital stay was also significantly shorter for previously vaccinated patients than for unvaccinated patients (8.5 vs. 14.29 days; P=0.007).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Recently, some authors have suggested that prior pneumococcal vaccination is associated with improved outcomes in vaccinated patients who develop CAP [22–24]. Our findings in HIV-infected patients are consistent with those previously published in non-HIV-infected patients. The composite outcome of death or admission to the ICU was significantly lower in previously vaccinated patients compared with unvaccinated patients. In fact, none of the vaccinated patients died or required admission to the ICU during their hospital stay for IPD. These data suggest that, despite the failure to prevent pneumococcal infection, prior PPV administration has a favourable impact in HIV-infected patients who develop IPD by improving clinical outcomes. The length of hospital stay was also significantly shorter in vaccinated patients. Regarding the presence of shock and also the severity in terms of clinical presentation and the development of empyema, among patients with bacteraemic pneumonia, the differences did not reach statistical significance but appeared to be clinically relevant.

In previous studies in non-HIV-infected patients, similar results were obtained. In a cohort of 554 adults hospitalized with community-acquired pneumococcal pneumonia (CAP), Mykietiuk et al. [23] reported a lower risk of bacteraemia and also better clinical outcomes, including a faster resolution of pneumonia symptoms, a lower rate of mortality and a shorter length of hospital stay, in prior PPV recipients compared with unvaccinated patients. Fisman et al. [22] studied a large cohort of 62,918 adults hospitalized with CAP and found that the prior receipt of pneumococcal vaccine was associated with decreased length of hospital stay and lower rates of severe complications and death during hospitalization. More recently, Johnstone et al. [21] analysed prospectively a cohort of 3415 adults hospitalized with CAP and found that prior 23-valent PPV vaccination was associated with a reduction in the rate of death or ICU admission in hospitalized adults with CAP. In this last study, a pre-specified sensitivity analysis restricted to patients who presented with bacteraemic pneumococcal pneumonia was conducted. Among 95 patients with bacteraemic pneumococcal pneumonia, none of the 10 previously vaccinated patients died or was admitted to the ICU, in comparison with 27 (32%) of 85 patients who had not received pneumococcal vaccine (P=0.06).

To our knowledge, these additional effects of the 23-valent PPV in patients who develop IPD have not previously been studied in HIV-infected patients. Our study focused on a cohort of HIV-infected patients with IPD in whom this effect of PPV might be expected to be particularly beneficial because of the high risk of complications related to IPD in this population.

In HIV-infected patients, as in the general population, the most common pneumococcal serotypes involved in IPD are those included in the 23-valent PPV [3,26]. In this study, it is worth noting that, in both the vaccinated and the unvaccinated groups, the most common causal serotypes were those included in the 23-valent PPV. This finding demonstrates that the vaccine failed to prevent pneumococcal infection in some prior vaccinated patients. However, the better clinical outcomes found in patients who had received the 23-valent PPV suggest that pneumococcal vaccination in HIV-infected patients could have significant clinical benefits, despite not conferring protection against IPD. It has been shown in animal models that a vaccine-generated immune response may facilitate opsonization, activate complement and promote bacterial phagocytosis. Therefore, it has been suggested that, although the antibody response following vaccination may not be sufficient to prevent pneumococcal infection and pneumonia, the partial immune response generated could attenuate the early inflammatory response and prevent early mortality and complications of pneumococcal infection [27,28]. In seven patients the 23-valent PPV was administered more than 5 years before the episode of IPD. None of these seven patients died or was admitted to the ICU, suggesting that the 23-valent PPV could retain this additional effect for a longer time.

Clinical guidelines recommend that re-immunization should be considered 5 years after the first dose of 23-valent PPV, specifically if the initial vaccination was given when the CD4 count was <200 cells/μL [20], although there are no available data supporting the clinical efficacy of revaccination. Moreover, some studies in patients with CD4 counts above 200 cells/μL and patients receiving HAART showed that revaccination did not improve the immune response over that achieved after the initial vaccination [29,30].

As a nonrandomized study, this observational study carries the limitations related to possible selection bias and confounding factors. The patients' records from 1996 to 1999 were reviewed retrospectively, and from 2000 onwards all data were collected prospectively. All 47 cases (29%) included in the period from 1996 to 1999 were studied retrospectively but clinical charts were carefully reviewed and the protocol was exactly the same throughout the study period, so we feel that the results have not been influenced by this fact. One problem for the analysis was the presence of recurrent episodes in some patients, which could influence the results. Three of these patients were vaccinated after the first episode of IPD, so the same patient could be counted as unvaccinated in one episode and as vaccinated in another. Because the different vaccination status of the same patient in different episodes of IPD could influence the outcomes, we decided to analyse each episode of IPD separately. In any case, in order to assess a possible selection bias related to the inclusion of patients with recurrent episodes, we carried out a new analysis after excluding all patients with repeated episodes of IPD (127 episodes in 127 patients) and the results did not change significantly (data not shown).

We found that patients who received PPV had higher CD4 cell counts and were more likely to be receiving HAART. The effectiveness of PPV in severely immunosuppressed patients has been broadly questioned and pneumococcal vaccination in HIV-infected patients is recommended in current guidelines, particularly in those with CD4 counts above 200 cells/μL. Although we only recorded the CD4 cell count at IPD presentation, it is possible that patients with severe immunosuppression were less likely to have received PPV. Nevertheless, we did not find significant differences in the proportion of patients with undetectable viral load. A decreased incidence of IPD associated with the use of HAART and immunological improvement has been reported [1–7]. In contrast, some studies showed that clinical presentation, severity of illness and mortality related to IPD were not associated with CD4 cell count or the use of HAART [6]. Thus, we believe that the beneficial effect of prior pneumococcal vaccination may not be attributable to a different severity of pneumococcal infection in patients with higher CD4 lymphocyte counts or those using HAART.

Among patients who had received PPV, there was only one patient with chronic liver disease. Chronic liver disease has been described as a risk factor for both IPD and a low response to PPV [31], so it could influence the clinical outcomes of IPD and the differences found could be overestimated. Because none of the previously vaccinated patients died or required ICU admission, we could not perform a multivariate analysis, so we attempted to avoid this possible selection bias by performing a new analysis excluding all patients with chronic liver disease. The differences between vaccinated and unvaccinated patients according to the composite outcome of death or admission to the ICU, admission to the ICU and length of hospital stay remained significant. Regarding the other clinical outcomes measured, the differences did not reach statistical significance, which could be explained by the reduction in the size of the sample. However, these differences appear to be clinically relevant.

Another difference between vaccinated and unvaccinated patients is that those who received the pneumococcal vaccine were less likely to be current or previous injecting drug users. Injecting drug use has been associated with a higher risk of IPD, and these findings, although they did not reach statistical significance, suggest that efforts should be made to increase vaccination rates in HIV-infected patients with other underlying high-risk conditions such as injecting drug use or chronic liver disease.

In summary, this study suggests that, as has been shown in non-HIV-infected patients, prior vaccination with PPV may provide some beneficial effects in HIV-infected patients by improving clinical outcomes in those who eventually develop IPD. Although 23-valent PPV fails to prevent IPD in some HIV-infected patients, previously vaccinated patients may have less severe illness, a lower risk of ICU admission, reduced in-hospital mortality and a shorter length of stay in hospital. We believe that these results support the current guidelines that recommend pneumococcal vaccination of HIV-infected adults, and emphasize the importance of this recommendation in order to decrease the morbidity and mortality related to pneumococcal infections in the HIV-infected population.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

This study was supported in part by Red de Investigación en SIDA (RIS, ISCIII-RETIC RD06/006).

Potential conflicts of interest. All authors: no conflicts.

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  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
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