23-Valent Pneumococcal Polysaccharide Vaccine Uptake in the United States Air Force HIV Program

Abstract

Streptococcus pneumoniae infection is a predominant cause of bacterial infection in HIV-infected individuals. However, reported rates of pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) are variable. We evaluated uptake of PPV23 in patients diagnosed with HIV between 1996 and 2012 (n = 507) in the United States Air Force, a centralized HIV program with free access to care including vaccines and medications. A total of 411 (81.1%) patients received at least 1 PPV23 dose. The PPV23 vaccination within 1 year of diagnosis was greater for those diagnosed between 2004 and 2012 (n = 184, 86%) compared with 1996 to 2003 (n = 104, 56.5%; P < .001). For those with ≥6 years of follow-up, receipt of a second recommended PPV23 dose was greater for those diagnosed between 1996 and 2003 (n = 52, 57.8%) compared with 2004 to 2012 (n = 9, 28.1%; P = .004). Although first PPV23 vaccination was high in recent years, process improvement efforts are underway to overcome barriers and improve uptake of pneumococcal vaccines in our program.

Keywords

HIV pneumococcal polysaccharide vaccine

Introduction

The administration of vaccines in order to prevent morbidity and mortality from vaccine-preventable illnesses is an important component of HIV primary care. Vaccines for Streptococcus pneumoniae (pneumococcus) are of considerable importance, since pneumococcus is a predominant cause of bacterial infection in individuals with HIV.¹ In the United States, the rate of invasive pneumococcal disease (IPD) in HIV-infected adults is estimated to be 173 of 100 000.² Without antiretroviral therapy (ART), the risk of IPD can be up to 300-fold higher.³ However, ART does not completely mitigate risk, as rates of IPD are 42-fold greater in those on ART than in HIV-uninfected persons.⁴

The 23-valent pneumococcal polysaccharide vaccine (PPV23) has been on the market in the United States since 1983 and offers clinical protection in up to 49% of adults with HIV infection.^1,5 The current Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) guidelines recommend HIV-infected adults receive PPV23 as soon as possible after diagnosis.⁶ Despite these recommendations, the rate of pneumococcal vaccination is variable in clinical settings, with reports ranging from 10% to 84%.^7

–10 The United States Air Force (USAF) utilizes a single-center model with free access to care and mandated visits for active duty personnel with HIV infection. Since this model mitigates or eliminates several barriers to HIV care, we hypothesized that PPV23 uptake would be relatively high in our center. We evaluated PPV23 uptake over a 17-year period, including first and second PPV23 doses for active duty members with long-term follow-up.

Materials and Methods

All active duty USAF members worldwide who are diagnosed with HIV infection have mandatory clinical evaluations at the HIV Medical Evaluation Unit at the San Antonio Military Medical Center (SAMMC) approximately every 6 months, with all travel and costs managed by the USAF. Clinical visits include HIV disease staging, laboratory evaluation, physical examination, immunizations, and HIV education. We conducted a retrospective review of clinical and vaccination data collected from electronic medical and laboratory records of active duty USAF members diagnosed with HIV infection between January 1, 1996, and December 31, 2012. Patients with one or more clinical program visits at SAMMC were included. Since this study aimed to evaluate vaccination practices in the USAF HIV program at SAMMC, patients who received PPV23 vaccination prior to the first SAMMC program visit were excluded (n = 4). This retrospective study was approved by the SAMMC institutional review board.

The primary outcome of this study was the proportion of patients administered PPV23 during 3 periods of observation, including 2 periods for primary vaccination and an additional period to evaluate repeat PPV23 vaccination. To capture overall uptake early after diagnosis, patients vaccinated at or within 6 months of their initial visit were analyzed. For patients with longitudinal follow-up (≥1 year), those vaccinated within 1 year of their initial visit were evaluated. Centers for Disease Control and Prevention ACIP guidelines also recommend a second PPV23 dose administered 5 years after the first dose.⁶ To study repeat vaccination, patients with ≥6 years of follow-up from their initial vaccination were evaluated for receipt of the second PPV23 dose. Patients who did not meet the criteria for longitudinal follow-up due to separation or retirement from military service were not available for second PPV23 analysis. Patients were divided into 2 groups according to calendar year of HIV diagnosis (1996-2003 versus 2004-2012). Chi-square and Mann-Whitney Wilcoxon tests were used where appropriate. Statistical analyses were performed using SAS 9.4 (SAS Institute), and P values <.05 were considered statistically significant.

Results

A total of 507 patients were included, with 218 (43%) diagnosed with HIV during 1996 to 2003 and 289 (57%) during 2004 to 2012 (Table 1). All patients, whether stationed in or outside the United States, received their initial evaluation a median of 37 (interquartile range [IQR], 25-50) days after HIV diagnosis. Patients were predominantly young enlisted males of European American or African American race/ethnicity in both the groups. The median viral load (log₁₀ copies/mL) at HIV diagnosis was significantly higher in the 2004 to 2012 group (4.42, IQR 3.90-4.94) compared with the 1996 to 2003 group (3.73, IQR 2.11-4.59; P < .001), but median CD4 count (cells/mm³) at diagnosis did not differ between the groups (510 cells/mm³, IQR 376-658 versus 516 cells/mm³, IQR 372-660, respectively; P = .89).

Table 1.

Characteristics of Active Duty USAF Members with HIV Infection.^a

Characteristics	All	Calendar Year of HIV Diagnosis		P Value
Characteristics	All	1996-2003	2004-2012	P Value
Number of patients	507 (100)	218 (43.0)	289 (57.0)	–
Gender, male	497 (98.0)	214 (98.2)	283 (97.9)	.69
Race/ethnicity^b				.25
European American	197 (44.1)	101 (46.3)	96 (41.9)
African American	195 (43.6)	97 (44.5)	98 (42.8)
Hispanic	34 (7.6)	13 (6.0)	21 (9.2)
Other	21 (4.7)	7 (3.2)	14 (6.1)
Military rank				.82
Officer	53 (10.5)	22 (10.1)	31 (10.7)
Enlisted	454 (89.5)	196 (89.9)	258 (89.3)
Median age at HIV diagnosis, years	27 (23-35)	29 (24-36)	26 (23-34)	.004
Median CD4 count at HIV diagnosis, cells/mm³	511 (374-658)	516 (372-660)	510 (376-658)	.89
Proportion with CD4 <200 cells/mm³ at HIV diagnosis	21 (4.2)	12 (5.5)	9 (3.1)	.19
Median VL at HIV diagnosis, log₁₀ copies/mL	4.28 (3.38-4.82)	3.73 (2.11-4.59)	4.42 (3.90-4.94)	<.001
Proportion with VL >100 000 copies/mL at HIV diagnosis^d	70 (14.7)	4 (2.1)	66 (22.8)	<.001
Median time from HIV diagnosis to first program visit, days	37 (25-50)	33 (22-47)	39 (26-54)	.02

Abbreviations: USAF, United States Air Force; VL, viral load.

^aAll data are represented as number (%) or median (interquartile range [IQR]).

^b60 (11.8%) patients did not report race/ethnicity data.

^cCD4 count at HIV diagnosis missing for 2 patients.

^d30 patients did not have VL data at HIV diagnosis.

Overall, 411 (81.1%) of 507 patients received at least 1 dose of PPV23 during the study period (Table 2). A greater proportion of patients received at least 1 vaccination in the 2004 to 2012 group (86.5%) compared with the 1996 to 2003 group (73.8%; P = .003). Among those who received PPV23, 305 (60.2%) patients were vaccinated at or within 6 months of their first clinic visit. A greater proportion of patients in the 2004 to 2012 group (75.1%) received PPV23 within 6 months after their first visit compared to the 1996 to 2003 group (40.4%; P < .001). There was no difference in PPV23 vaccination in patients with a CD4 count <200 cells/mm³ at HIV diagnosis, with 5 (41.6%) of 12 and 5 (55.5%, P = .54) of 9 patients vaccinated in the 1996 to 2003 and 2004 to 2012 groups, respectively. Similar vaccine uptake was observed for those with viral load >100 000 copies/mL at HIV diagnosis in the 1996 to 2003 (3 of 4 patients, 75%) and 2004 to 2012 groups (56 of 66 patients, 84%; P = .67). The 2004 to 2012 group also received their first vaccination comparatively sooner during or after their first clinic visit (median 4 months, IQR 0.4-13.4 versus 0.3 months, IQR 0.3-0.7; P < .001). Of those with ≥1 year of follow-up after initial visit, a greater proportion of patients received their first PPV23 dose within 1 year of their initial visit in the 2004 to 2012 group (86%) compared to the 1996 to 2003 group (56.5%; P < .001).

Table 2.

Characteristics of PPV23 Vaccination.^a

Characteristics	All	Calendar Year of HIV Diagnosis		P Value
Characteristics	All	1996-2003	2004-2012	P Value
All patients	507	218	289	–
Received ≥1 dose of PPV23	411 (81.1)	161 (73.8)	250 (86.5)	.003
Interval 1: Within 6 months of first visit
Received first PPV23 dose	305 (60.2)	88 (40.4)	217 (75.1)	<.001
Interval 2: Within 1 year of first visit
Patients with ≥1 year follow-up since first visit	398 (78.5)	184 (84.4)	214 (74.1)	.005
Received first PPV23 dose	288 (72.4)	104 (56.5)	184 (86.0)	<.001
Interval 3: Within 6 years after first PPV23 dose
Patients with ≥6 years follow-up since first PPV23 vaccination	122 (24.1)	90 (41.3)	32 (11.1)	<.001
Received second PPV23 vaccination	61 (50.0)	52 (57.8)	9 (28.1)	.004

Abbreviation: PPV23, 23-valent pneumococcal polysaccharide vaccine.

^aAll data are represented as number (%).

Overall, 61 (50%) of 122 patients with ≥6 years of follow-up after first PPV23 vaccination received a second dose (Table 2). The 1996 to 2003 group (41.3%) had a higher proportion of patients with ≥6 years of follow-up after first PPV23 vaccination than the 2004 to 2012 group (11.1%, P < .001); however, the majority of those in the latter group had insufficient follow-up time for evaluation since the study period ended in 2012. The second PPV23 vaccination proportion was higher in the 1996 to 2003 group compared with the 2004 to 2012 group (57.8% versus 28.1%; P = .004). There was no difference in the median duration between first and second PPV23 vaccination for the 1996 to 2003 (68.1 months, IQR 60.1-77.2) and 2004 to 2012 groups (62.1 months, IQR 59.5-70.9; P = .41).

Discussion

Despite notable decline in the incidence of IPD with the use of ART in HIV-infected patients, associated morbidity and mortality remain high in this population.^1,4 Although there is no uniform agreement on the specific efficacy and durability of pneumococcal vaccination in HIV-infected patients, moderate clinical evidence supports its use in this at-risk population.^1,11 Since PPV23 is well tolerated, inexpensive, and provides coverage against the most common IPD-related serotypes, pneumococcal vaccination continues to be recommended in HIV-infected patients.^2,12 In accordance with these recommendations, we observed an overall vaccination uptake of 81% during the 17-year study period in the USAF population. However, vaccine uptake was greatest in recent years, with 87% of patients diagnosed between 2004 and 2012 receiving 1 or more PPV23 doses.

There is a wide range of pneumococcal vaccination rates for HIV-infected patients in the published literature.^7,8 Previous studies with some of the highest reported vaccination rates were also associated with federally affiliated medical health-care systems in the United States. For example, 1 study reported a 70% vaccination rate for 1411 patients enrolled in 4 states (Maryland, Illinois, New York, and Georgia) under the US Health Resources and Services Administration’s Ryan White Title III system.⁸ However, these vaccination rates may not be reflective of all Ryan White Title III system clinics, as patients were limited to those seen within the past 6 months and only from study sites with expressed interest in study participation. The Veterans Aging (VA) Cohort 5-Site Study, which aimed to evaluate the impact of PPV23 on the incidence of pneumonia, evaluated vaccination status for 1626 patients. Among this population, 69% of HIV-infected patients were categorized as vaccinated based on PPV23 vaccination within the prior 3 or 2 years after the study survey was administered.¹³ However, only 82% of HIV-infected patients indicated using the VA system for outpatient care. In contrast to the populations in these studies, our USAF population received centralized care at a single center, allowing for complete data capture as well as long-term follow-up for those continuing on active military service. In addition, the unique nature of the centralized, military-funded, and military-operated USAF HIV program likely reduced previously proposed barriers to vaccination in HIV-infected adults, including access to care, loss to follow-up, financial barriers, insurance coverage, cost, and provider expertise.¹⁴

The uptake of PPV23 approached 90% in the current era which is, to our knowledge, among the highest reported. Our results also demonstrate a relatively short latency to first PPV23 after initial visit, with a majority of patients receiving their initial dose within the first year. Analysis of the 2 subgroups based on calendar year of HIV diagnosis (1996-2003 versus 2004-2012) showed an improvement in the proportion of patients vaccinated within 6 and 12 months in the latter group. There are several potential explanations for this observation. The military transitioned to a global electronic medical record with vaccination documentation in the mid-2000s, which may have contributed to improved tracking and uptake of vaccines. Other unmeasured factors may include enhanced knowledge or application of recommendations by providers as well as clinic process improvement initiatives.

Differences in overall PPV23 vaccination between the 2 subgroups were not attributable to the proportion of patients with low CD4 counts (<200 cells/mm³) or high viral load (>100 000 copies/mL), 2 factors that had previously been suggested to limit vaccine efficacy and could theoretically cause providers to delay PPV23 administration.^15
–17 This may reflect adherence to the notion that delaying vaccination until several months after ART initiation allows for immune reconstitution and viral suppression that may improve vaccine response. However, recent studies showed no significant improvement in laboratory markers of PPV23 response when immunization is delayed until after ART, and no correlation between viral load, postvaccination immunoglobulin G, and opsonophagocytic titers (OPT) was observed.^18,19 This is in contrast to hepatitis B virus (HBV) vaccine, where responsiveness, as measured by antibody to HBV surface antigen, has been shown to be 2-fold greater with use of ART in HIV-infected patients.²⁰

Despite high vaccine uptake for the first PPV23 dose, only 50% of eligible patients received the second PPV23 vaccination. Although second vaccination was significantly lower in the 2004 to 2012 group (28%) compared to the 1996 to 2003 group (58%), there were only 9 evaluable cases in the latter group due to the study period ending in 2012. In contrast to other clinical practices, our single-center model of HIV care and worldwide electronic medical record system enables USAF providers to track vaccinations, despite patient relocations. Regardless, our data show that uptake of the second PPV23 dose is much lower than the first dose, and there are no published studies evaluating uptake of the second PPV23 dose in HIV-infected patients. A recent study highlighted the potential benefit of PPV23 revaccination by demonstrating a significant rise in OPT above previously used vaccine response threshold (≥8) in HIV-infected patients revaccinated with PPV23 after 5 years.²¹ As a result, the USAF program is conducting quality improvement initiatives, including in-services to educate providers, nursing chart review, and display of immunization schedules in patient examination rooms. The future enhancement of our electronic medical record system capabilities to track immunizations and provide electronic notification to clinicians is likely to further improve vaccine uptake.

There are several limitations to this retrospective study. Specific clinical or patient-oriented reasons for nonvaccination were not identified for a limited number of patients who did not receive PPV23. The most recent ACIP guidelines recommend both PPV23 and 13-valent pneumococcal conjugate vaccine (PCV13) vaccination.² However, PCV13 was not evaluated, as recommendations were published in June 2012 and limited observations were available during the study period.

The USAF program has features that should otherwise be ideal for successful implementation of recommended vaccines, including free access to care and vaccines, a single-site program for HIV clinical evaluations, and a global electronic medical record system. However, there continue to be challenges to optimizing vaccine uptake, and opportunities for improvement remain for increasing adherence to ACIP guidelines, particularly for the second PPV23 dose. Since PCV13 is also recommended for those who received the first PPV23 dose, it is important to closely track the timing and administration of both pneumococcal vaccines in order to prevent delays in HIV-infected patients.

Footnotes

Authors’ Note

The views expressed herein are those of the authors and do not reflect the official policy or position of San Antonio Military Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, and Department of Defense or the U.S. Government.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Cordonnier

Averbuch

Maury

Engelhard

. Pneumococcal immunization in immunocompromised hosts: where do we stand? Expert Rev Vaccines. 2014;13(1):59–74.

Centers for Disease Control and Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61(40):816–819.

Schuchat

Broome

Hightower

Costa

Parkin

. Use of surveillance for invasive pneumococcal disease to estimate the size of the immunosuppressed HIV-infected population. JAMA. 1991;265(24):3275–3279.

Nunes

von Gottberg

de Gouveia

. The impact of antiretroviral treatment on the burden of invasive pneumococcal disease in South African children: a time series analysis. AIDS. 2011;25(4):453–462.

Breiman

Keller

Phelan

. Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients. Arch Intern Med. 2000;160(17):2633–2638.

Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) recommended immunization schedules for person aged 0 through 18 years and adult aged 19 years and older. MMWR Suppl. 2013;62(1):1.

Hunter

Post

. An audit of pneumococcal and hepatitis vaccination in an outpatient HIV clinic. Sex Health. 2012;9(5):495–496.

Kaplan

Parham

Soto-Torres

. Adherence to guidelines for antiretroviral therapy and for preventing opportunistic infections in HIV-infected adults and adolescents in Ryan White-funded facilities in the United States. J Acquir Immune Defic Syndr. 1999;21(3):228–235.

Belda

Littlejohn

Pedersen

Valle-Rivera

Tyndall

. Adoption of the chronic care model to improve HIV care. Can Fam Physician. 2013;59(6):650–657.

10.

Rock

Sadlier

Fitzgerald

. Epidemiology of invasive pneumococcal disease and vaccine provision in a tertiary referral center. Eur J Clin Microbiol Infect Dis. 2013;32(9):1135–1141.

11.

Pedersen

Lohse

Ostergaard

Sogaard

. The effectiveness of pneumococcal polysaccharide vaccination in HIV-infected adults: a systematic review. HIV Med. 2011;12(6):323–333.

12.

Munier

de Lastours

Varon

Donay

Porcher

Molina

. Invasive pneumococcal disease in HIV-infected adults in France from 2000 to 2011: antimicrobial susceptibility and implication of serotypes for vaccination. Infection. 2013;41(3):663–668.

13.

Rodriguez-Barradas

Goulet

Brown

. 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. 2008;46(7):1093–1100.

14.

Bailey

Smith

Sands

. Hepatitis B vaccine: a seven-year study of adherence to the immunization guidelines and efficacy in HIV-1-positive adults. Int J Infect Dis. 2008;12(6):e77–e83.

15.

Center for Disease Control and Prevention. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR Recomm Rep. 1999;48(rr-10):1–59, 61–66.

16.

Dworkin

Ward

Hanson

Jones

Kaplan

; Adult and Adolescent Spectrum of HIV Disease Project. Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination. Clin Infect Dis. 2001;32(5):794–800.

17.

Teshale

Hanson

Flannery

. Effectiveness of 23-valent polysaccharide pneumococcal vaccine on pneumonia in HIV-infected adults in the United States, 1998-2003. Vaccine. 2008;26(46):5830–5834.

18.

Leggat

Iyer

Ohtola

. Response to pneumococcal polysaccharide vaccination in newly diagnosed HIV-positive individuals. J AIDS Clin Res. 2015;6(2). pii:419.

19.

Rodriguez-Barradas

Serpa

Munjal

. Quantitative and qualitative antibody responses to immunization with the pneumococcal polysaccharide vaccine in HIV-infected patients after initiation of antiretroviral treatment: results from a randomized clinical trial. J Infect Dis. 2015;211(11):1703–1711.

20.

Landrum

Huppler Hullsiek

Ganesan

. Hepatitis B vaccine responses in a large U.S. military cohort of HIV-infected individuals: another benefit of HAART in those with preserved CD4 count. Vaccine. 2009;27(34):4731–4738.

21.

Iyer

Leggat

Ohtola

. Response to pneumococcal polysaccharide vaccination in HIV-positive individuals on long term highly active antiretroviral therapy. J AIDS Clin Res. 2015;6(2):pii: 421.