Impact of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease Among Adults With HIV—United States, 2008–2018 : JAIDS Journal of Acquired Immune Deficiency Syndromes

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Epidemiology

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease Among Adults With HIV—United States, 2008–2018

Kobayashi, Miwako MD, MPHa; Matanock, Almea MD, MSa; Xing, Wei MSb; Adih, William K. MD, DrPH, MPHc; Li, Jianmin DPEc; Gierke, Ryan MPHa; Almendares, Olivia MSPHa; Reingold, Arthur MDd; Alden, Nisha MPHe; Petit, Susan MPHf; Farley, Monica M. MDg; Harrison, Lee H. MDh; Holtzman, Corinne MPHi; Baumbach, Joan MD, MPH, MSj; Thomas, Annk; Schaffner, William MDl; McGee, Lesley PhDa; Pilishvili, Tamara PhD, MPHa

Author Information

aDivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA;

bWeems Design Studio Inc, Decatur, GA;

cDivision of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA;

dBerkeley School of Public Health, University of California, Berkeley, CA;

eColorado Department of Public Health and Environment, Denver, CO;

fConnecticut Department of Public Health, Hartford, CT;

gDepartment of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, GA;

hDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;

iMinnesota Department of Health, St. Paul, MN;

jNew Mexico Department of Health, Santa Fe, NM;

kOregon Department of Human Services, Portland, OR; and

lDepartment of Health Policy, Vanderbilt University School of Medicine, Nashville, TN.

Correspondence to: Miwako Kobayashi, MD, MPH, Division of Bacterial Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329, MS H24-6 (e-mail: [email protected])

M. Kobayashi and A. Matanock are co-first authors.

Presented in part at the IDWeek 2021 virtual conference; September 29, 2021,–October 3, 2021

W.S. served as a consultant for VBI Vaccines. L.H.H. served as a consultant for GSK, Merck, Pfizer, and Sanofi Pasteur. The remaining authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

JAIDS Journal of Acquired Immune Deficiency Syndromes 90(1):p 6-14, May 1, 2022. | DOI: 10.1097/QAI.0000000000002916

Abstract

Background: 

People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older.

Methods: 

We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017–2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs.

Results: 

In 2008–2009 and 2017–2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19–64 years (94.7%–97.4% vs. 56.0%–60.1%) and non-Hispanic Black people (62.5%–73.0% vs. 16.7%–19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: −47.7 to −32.3) and 72.5% (95% confidence interval: −78.8 to −65.6), respectively. In 2017–2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively.

Conclusions: 

Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH.

INTRODUCTION

Despite the introduction of highly active antiretroviral therapy, people with HIV (PWH) continue to be at increased risk of invasive pneumococcal disease (IPD).1–3 PWH have a slow and incomplete therapy-associated recovery of protective immune functions, and impaired immunity persists even in individuals who maintain CD4 T-cell levels of ≥500 cells/μL.4–6

Two pneumococcal vaccines are currently recommended for use for PWH in the United States: the 23-valent pneumococcal polysaccharide vaccine (PPSV23) and the 13-valent pneumococcal conjugate vaccine (PCV13). PPSV23 is recommended for individuals aged 2 years or older with certain underlying conditions, including PWH and for all adults aged 65 years or older, and has been available since the 1980s.7,8 PCV13 was recommended in 2010 for routine use among children younger than 5 years and replaced the 7-valent PCV (PCV7).9 PCV use in US children dramatically reduced IPD incidence not only in children but also in unvaccinated adults10–13 because of indirect effects from vaccination of children. Our previous analyses of 1998–2007 data showed that IPD incidence among people with AIDS (used in place of PWH because the number of PWH could not be obtained for the entire study period) decreased, suggesting that PWH also benefited from indirect effects2,3; however, IPD incidence among PWH aged 18–64 years was still 40 times higher than in those without HIV infection.

PCV use in US adults was first recommended in 2012 when the Advisory Committee on Immunization Practices recommended routine use of PCV13 for adults aged 19 years or older with immunocompromising conditions, including HIV, functional or anatomic asplenia, cerebrospinal fluid leaks, or cochlear implants, in series with PPSV23.14 In 2014, all adults aged 65 years or older were recommended to receive PCV13 in series with PPSV23, which was changed to a recommendation based on shared clinical decision-making in 2019 in adults without immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leaks, or cochlear implants.15,16 We evaluated the population-level impact of current US PCV13 policy on IPD incidence among PWH aged 19 years or older compared with those not diagnosed with HIV (non-PWH).

METHODS

Surveillance Methods

IPD cases were identified through the Active Bacterial Core surveillance (ABCs), an active, laboratory-based and population-based surveillance platform for invasive bacterial diseases in select counties of 10 states across the United States.17 Medical records were abstracted to collect demographic and clinical informations on each case, including HIV infection status.18,19 Pneumococcal isolates from ABCs cases were serotyped at the Minnesota Department of Health or the Centers for Disease Control and Prevention (CDC) Streptococcus Laboratory by Quellung, polymerase chain reaction, or whole-genome sequencing (2015–2018). For this study, we included cases reported during 2008–2018 among adults aged 19 years or older residing in ABCs catchment areas in 9 states (CA, CT, CO, GA, MD, MN, New Mexico, OR, or TN) (see Table, Supplemental Digital Content 1, https://links.lww.com/QAI/B797).

Definitions

An IPD case was defined as isolation of Streptococcus pneumoniae from a normally sterile site (eg, blood and cerebrospinal fluid) from a surveillance area resident. We grouped pneumococcal serotypes for analysis of disease trends into the following categories: (1) PCV13 types defined as the 13 serotypes contained in PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and serotype 6C because of cross-protection from the serotype 6 A antigen20; (2) PPSV23 unique types defined as the 11 serotypes contained in PPSV23 but not in PCV13 (serotypes 2, 8, 9N, 10A, 11A, 12F, 15B/C, 17F, 20, 22F, and 33F); and (3) non-vaccine types (NVTs), which included all other serotypes. Given the recent licensure of the 15-valent and 20-valent PCVs (PCV15 and PCV20) for adults,21,22 we evaluated the contribution of additional serotypes included in PCV15 but not PCV13 (PCV15-unique types: 22F and 33F) and PCV20 but not PCV15 (PCV20-unique types: 8, 10A, 11A, 12F, and 15B/C) to IPD in this population. AIDS was defined as ever having a diagnosis of AIDS or CD4 count of <200 cells/mm3.

Statistical Methods

Characteristics of IPD cases were summarized by HIV status and by the study period: baseline before PCV13 introduction in the pediatric immunization program (2008–2009) and before (2011–2012) and after (2017–2018) PCV13 recommendation in immunocompromised adults. To estimate IPD incidence per 100,000 adults among PWH and non-PWH, we used 2 data sources for population denominators. For PWH, we used the number of adults aged 19 years or older with known HIV infection in the ABCs catchment area17 (see Supplemental Digital Content 1, https://links.lww.com/QAI/B797). For non-PWH, we used the US Census estimates for ABCs catchment area, less the number of PWH in the same ABCs catchment area. Overall and serotype-specific or group-specific IPD incidence for PWH and non-PWH was stratified by age groups (19–64 years and 65 years or older) and race and ethnicity (non-Hispanic Black, non-Hispanic White, and Hispanic). For IPD incidence calculation, simple proportions were used to impute missing serotype and race/ethnicity data (see Supplemental Digital Content 1, https://links.lww.com/QAI/B797).

Incidence at the baseline period (2008–2009) was compared with incidence before (2011–2012) and after (2017–2018) PCV13 introduction in immunocompromised adults, both after PCV13 introduction for children. Percent changes of incidence rates were calculated as 1–(IPD incidence post-PCV13)/(IPD incidence at baseline). The incidence rate ratio (IRR) was calculated to compare the incidence rate of PWH with that of non-PWH. The variance of IPD incidence was calculated using the assumption that IPD cases followed a Poisson distribution. We drew 10,000 values from the distribution of IPD cases and reported the 95% confidence interval (CI) of the estimates based on the upper and lower 2.5th percentile of the 10,000 calculated percent changes and IRR.

We compared the distribution of PCV13 types, serotypes unique to PPSV23, and the most common NVTs bewteen 2008–2009 and 2017–2018 for both PWH and non-PWH using the χ2 test. To account for multiple comparisons (n = 30), we used a Bonferroni correction, where a P value of <0.002 (0.05/30) was considered statistically significant. Analyses were performed using SAS version 9.4 (SAS Institute, Inc.).

RESULTS

Description of IPD Cases Pre-PCV13 and Post-PCV13 Introduction by HIV Status

During 2008–2009, a total of 29,668 IPD cases were reported, including 2440 (8.2%) among PWH. Characteristics of IPD cases in 2008–2009 (n = 6548), 2011–2012 (n = 5226), and 2017–2018 (n = 5169) are presented in Table 1. Of IPD cases among PWH in 2008–2009, 49.8% (275/552) ever had an AIDS diagnosis compared with 55.8% (232/416) in 2017–2018. For all study periods, the proportions of adults aged 19–64 years (95%–97% in PWH vs. 56%–60% in non-PWH), men (60%–67% in PWH vs. 51%–53% in non-PWH), and non-Hispanic Black people (63%–73% in PWH vs. 17%–19% in non-PWH) were higher in IPD cases in PWH compared with non-PWH (Table 1). The proportion with ≥1 chronic medical conditions or people who smoke was similar between the 2 groups (63%–67% in PWH vs. 64%–69% in non-PWH) (Table 1). The proportion with ≥1 immunocompromising conditions other than HIV (ie, sickle cell disease, asplenia, congenital or acquired immunodeficiency, organ transplantation, dialysis, and malignancy) was higher in IPD cases in non-PWH compared with PWH and increased steadily for both groups through 2017–2018 (PWH 25% vs. non-PWH 34%) compared with baseline years (PWH 16% vs. non-PWH 26%).

Table 1. - Characteristics of Adults With and Without Known HIV Infection by Study Period, ABCs 2008–2018
Pre-PCV13 in Both Children and Adults 2008–2009 (N = 6548) Post-PCV13 in Children and Pre-PCV13 in Adults 2011–2012 (N = 5226) Post-PCV13 2017–2018 (N = 5169)
PWH Non-PWH PWH Non-PWH PWH Non-PWH
No. of patients 552 5996 443 4783 416 4753
Median age in year (range) 46 (20–76) 60 (19–104) 48 (19–81) 62 (19–100) 51 (20–74) 63 (19–105)
Age group
 19–64 years, n(%) 538 (97) 3602 (60) 430 (97) 2703 (57) 394 (95) 2661 (56)
 65 years or older, n (%) 14 (3) 2394 (40) 13 (3) 2080 (43) 22 (5) 2092 (44)
Sex
 Male, n (%) 331 (60) 3037 (51) 271 (61) 2448 (51) 286 (69) 2520 (53)
 Female, n (%) 221 (40) 2955 (49) 172 (39) 2334 (49) 130 (31) 2232 (47)
 Unknown, n (%) 0 4 (<1) 0 1 (<1) 0 1 (<1)
Race and ethnicity†
 Hispanic, n (%) 35 (6) 414 (7) 25 (6) 352 (7) 41 (10) 429 (9)
 White, non-Hispanic, n (%) 91 (16) 3609 (60) 85 (19) 3125 (65) 97 (23) 2905 (61)
 Black, non-Hispanic, n (%) 403 (73) 1014 (17) 315 (71) 799 (17) 260 (63) 912 (19)
 Others‡, n (%) 8 (1) 264 (4) 6 (1) 215 (4) 10 (2) 289 (6)
 Unknown, n (%) 15 (3) 695 (12) 12 (3) 292 (6) 8 (2) 218 (5)
Ethnicity
 Hispanic, n (%) 35 (6) 414 (7) 25 (6) 352 (7) 41 (10) 429 (9)
 Non-hispanic, n (%) 284 (51) 2604 (43) 276 (62) 2856 (60) 324 (78) 3599 (76)
 Unknown, n (%) 233 (42) 2978 (50) 142 (32) 1575 (33) 51 (12) 725 (15)
Ever diagnosed with AIDS* 275 (49.8) NA 178 (40.2) NA 232 (55.8) NA
Pneumonia with bacteremia, n (%)§ 444 (80) 4517 (75) 342 (77) 3621 (76) 334 (80) 3457 (73)
Meningitis, n (%)§ 29 (5) 312 (5) 30 (7) 288 (6) 15 (4) 315 (7)
Bacteremia w/o focus, n (%) 69 (13) 907 (15) 51 (12) 604 (13) 46 (11) 663 (14)
Deaths, n (%)
 19–64 years, n (%) 37/538 (7) 336/3602 (9) 21/430 (5) 247/2703 (9) 14/394 (4) 291/2661 (11)
 65 years or older, n(%) 3/14 (21) 397/2394 (17) 2/13 (15) 322/2080 (15) 0/22 (0) 296/2092 (14)
Other chronic medical conditions‖, n(%) 360 (65) 3830 (64) 298 (67) 3297 (69) 264 (63) 3205 (67)
Other immunosuppressive condition, n(%) 88 (16) 1558 (26) 82 (19) 1486 (31) 102 (25) 1623 (34)
*AIDS defined as ever having a diagnosis of AIDS or CD4 count <200.
†Race and ethnicity groups were assigned by first identifying those with Hispanic ethnicity. Those who were not Hispanic (including those with unknown or missing ethnicity) were categorized by their race.
‡Others include American Indian, Alaska Native, Asian, Pacific Islander, other races not otherwise specified, and multiple races recorded.
§Not mutually exclusive. Diagnosis based on clinical diagnosis and detection of S. pneumoniae rom a normally sterile site.
‖Defined as chronic medical conditions (chronic heart, lung, liver disease, diabetes mellitus, cerebrospinal fluid leaks, cochlear implants, alcoholism, and cigarette smoking) for which 23-valent pneumococcal polysaccharide vaccine (PPSV23) alone is recommended.
Defined as other immunosuppressive conditions besides HIV (sickle cell disease, asplenia, congenital or acquired immunodeficiency including HIV, organ transplantation, dialysis, and malignancy) for which PCV13 is recommended in series with PPSV23.

Pneumonia with bacteremia was the most common syndrome, associated with 77%–80% of IPD cases among PWH, and 73%–76% of those in non-PWH. The case fatality ratio in adults aged 65 years or older (0%–21%) was generally higher compared with adults aged 19–64 years (4%–11%) in both PWH and non-PWH, although IPD cases in PWH aged 65 years or older was small.

Changes in IPD Incidence

At baseline (2008–2009), IPD incidence among PWH was 306.7 per 100,000 (Table 2) and was higher among those aged 19–64 years (308.6 per 100,000) compared with those aged 65 years or older (248.5 per 100,000). Overall IPD incidence declined by 40.3% to 183.0 per 100,000 in 2017–2018 compared with baseline (Table 2). In non-PWH, overall IPD incidence was 15.2 per 100,000 persons at baseline and was 3.6 times higher in those aged 65 years or older compared with those aged 19–64 years (39.2 and 10.8 per 100,000, respectively). Overall IPD incidence declined by 28.2% from baseline to 10.9 per 100,000 in 2017–2018.

Table 2. - Invasive Pneumococcal Disease (IPD) Incidence Among Adults 19 Years or Older With or Without HIV Diagnosis by the Age and Serotype Group, 2008–2018
Incidence Among Adults Diagnosed with HIV Cases/100,000 Persons Incidence Among Adults Diagnosed without HIV Cases/100,000 Persons
2008-2009 (a) 2011-2012 (b) % Change (95% CI)
(b) – (a)		 2017-2018 (c) % Change (95% CI)
(c) – (a)		 2008-2009 (a) 2011-2012 (b) % Change (95% CI)
(b) – (a)		 2017-2018 (c) % Change (95% CI)
(c) – (a)
≥19 years or older (All)
 All IPD 306.7 222.8 −27.4% −36.0 to −17.7 183.0 −40.3% −47.7 to −32.3 15.2 11.8 −22.6% −25.5 to −19.6 10.9 −28.2% −30.9 to −25.5
 PCV13* IPD 143.9 80.0 −44.4% −54.6 to −32.5 39.6 −72.5% −78.8 to −65.6 8.3 4.8 −42.2% −45.4 to −38.9 3.1 −62.2% −64.5 to −59.8
 PPSV23-unique† IPD 73.9 75.4 2.6% −19.2 to 29.6 79.2 7.5% −14.6 to 35.2 4.0 4.2 5.3% −1.7 to 12.7 4.5 12.6% 5.2 to 20.0
  PCV15-unique‡ 22.8 20.3 −10.8% −43.9 to 38.2 20.3 −10.8% −42.0 to 35.9 1.6 1.7 8.1% −3.1 to 20.4 1.5 −6.9% −16.6 to 3.7
  PCV20-unique§ 27.8 34.6 24.5% −13.6 to 81.0 31.2 12.4 −20.8 to 62.6 1.6 1.7 3.5% −7.2 to 15.3 1.8 11.7% 0.7 to 23.7
 NVT IPD 90.0 66.9 −24.9% −41.1 to −6.4 64.2 −28.0% −43.3 to −10.5 2.9 2.8 −5.0% −12.6 to 3.1 3.3 12.1% 4.0 to 21.3
19–64 years
 All IPD 308.6 226.6 −26.6% −35.4 to −16.7 191.9 −37.8% −45.6 to −29.2 10.8 8.0 −26.4% −30.0 to −22.7 7.6 −30.1% −33.5 to −26.5
 PCV13 IPD 142.3 81.7 −42.5% −53.2 to −30.0 40.4 −71.7% −78.3 to −64.1 6.1 3.3 −45.8% −49.6 to −41.6 2.3 −62.2% −65.3 to −59.1
 PPSV23-Unique IPD 74.6 76.4 2.4% −19.3 to 30.7 84.3 13.0% −10.2 to 43.0 3.0 3.1 3.1% −5.5 to 12.5 3.4 15.1% 5.8 to 25.1
 NVT IPD 91.8 68.5 −25.4% −41.0 to −5.7 67.2 −26.8% −42.2 to −7.7 1.7 1.6 −8.3% −15.5 to 6.9 1.8 6.6% −4.7 to 19.2
≥65 years or older
 All IPD 248.5 144.0 −42.0% −75.0 to 31.1 99.9 −59.8% −79.3 to −15.2 39.2 31.3 −20.2% −24.8 to −15.4 25.1 −36.0% −39.6 to −32.2
 PCV13 IPD 177.5 44.3 −75.0% −95.8 to −25.1 27.2 −84.7% −96.1 to −57.4 20.1 12.3 −38.9% −44.1 to −33.2 6.6 −67.1% −70.3 to −63.7
 PPSV23-Unique IPD 53.2 55.4 4.0% −82.2 to 337.0 36.3 −31.8% −80.8 to 181.4 9.7 10.1 4.8% −6.3 to 17.2 9.1 −5.5% −15.0 to 5.3
 NVT IPD 17.7 33.2 87.3% −100.0 to 274.5 36.3 104.7% −61.2 to 232.6 9.5 8.9 −6.0% −16.3 to 5.6 9.4 −1.1% −11.0 to 10.2
*Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, and 6C.
†Serotypes 2, 8, 9N, 10A, 11A, 12F, 15B/C, 17F, 20, 22F, and 33F.
‡Serotypes 22F and 33F.
§Serotypes 8, 10A, 11A, 12F, and 15B/C.

PCV13-type IPD incidence in PWH declined by 72.5% (from 143.9 to 39.6 per 100,000) from baseline to 2017–2018 (Fig. 1 and Table 2), although incidence was stable during 2014–2018 (Fig. 1). Reduction in PCV13-type IPD incidence was greater (−84.7%; from 177.5 to 27.2 per 100,000) in those aged 65 years or older compared with those aged 19–64 years (−71.7%; from 142.3 to 40.4 per 100,000); moreover, PCV13-type IPD incidence in those aged 19–64 years remained higher compared with those aged 65 years or older. In non-PWH, PCV13-type IPD incidence declined by 62.2% (from 8.3 to 3.1 per 100,000) from baseline to 2017–2018, and the percent reduction was similar between age groups.

F1
FIGURE 1.:
Annual invasive pneumococcal disease incidence by the serotype group among adults aged 19 years or older with HIV infection, 2008–2018.

In PWH, a 28.0% (from 91.1 to 65.1 per 100,000) reduction in NVT-IPD incidence was observed, with year-by-year variation in incidence (Fig. 1), and the reduction was significant only among adults aged 19–64 years. Changes in PPSV23-unique IPD incidence was not significant. In non-PWH, NVT-IPD incidence (from 3.0 to 3.4 per 100,000) and PPSV23-unique IPD incidence (from 3.9 to 4.4 per 100,000) increased, although trends varied by age groups (Table 2).

Given that serotype distribution may differ by HIV status and by race/ethnicity, we compared the serotype distribution by HIV status and race/ethnicity before and after imputing missing values, and the serotype distributions were similar (see Table 1, Supplemental Digital Content, https://links.lww.com/QAI/B798). Therefore, IPD incidence calculation by race/ethnicity used imputed data. In PWH, overall IPD incidence at baseline was highest among non-Hispanic Black people (517.8 per 100,000) and lowest among non-Hispanic White people (142.9 per 200,000) (see Table 2, Supplemental Digital Content, https://links.lww.com/QAI/B798). The largest reduction in PCV13-type IPD incidence was observed in non-Hispanic Black people (from 231.4 to 42.4 per 100%,000%; 81.7% reduction); at baseline, PCV13-type incidence in non-Hispanic Black people was 2.8 times higher than that of non-Hispanic White people, but in 2017–2018, PCV13-type IPD incidence between non-Hispanic Black people and non-Hispanic White people was similar. However, overall IPD incidence in non-Hispanic Black people remained nearly twice as high in 2017–2018 as that in non-Hispanic White people (249.9 vs. 131.4 per 100,000). In non-PWH, non-Hispanic Black people also had the highest IPD incidence at baseline and in 2017–2018 (20.2 and 13.8 per 100,000, respectively). PCV13-IPD incidence declined in all race/ethnicity groups (non-Hispanic Black people, non-Hispanic White people, and Hispanics), and PCV13-IPD incidence rates were similar across groups in 2017–2018.

Comparing Incidence Between Adults With and Without HIV

At baseline, IRR of overall IPD between PWH and non-PWH was 20.2 (95% CI: 18.4 to 22.0) and declined to 16.8 (95% CI: 15.1 to 18.5) in 2017–2018 (Table 3). IRRs were lower in 2017–2018 compared with baseline in both age groups but remained higher among adults aged 19–64 years (2008–2009: 28.6 and 2017–2018: 25.4) compared with adults aged 65 years or older (2008–2009: 6.3 and 2017–2018: 4.0). PCV13-type IRR declined, most notably after 2011–2012 (17.3 in 2008–2009, 16.7 in 2011–2012, and 12.6 in 2017–2018). Similar trends were noted in adults aged 19–64 years. NVT IRR also declined (30.0 to 19.6) because of the decline in adults aged 19–64 years (53.7 to 36.9).

TABLE 3. - IRR Comparing Incidence Among Adults 19 Year or Older Diagnosed With HIV to Those Without HIV by the Age and Vaccine-Serotype Group, 2008–2018
  IRR Among Adults With and Without a Diagnosis of HIV
2008–2009 IRR (95% CI) 2011–2012 IRR (95% CI) 2017–2018 IRR (95% CI)
19 years or older (all)
 All IPD 20.2 18.4 to 22.0 18.9 17.1 to 20.8 16.8 15.1 to 18.5
 PCV13* IPD 17.4 15.1 to 19.6 16.7 14.1 to 19.4 12.6 9.9 to 15.3
 PPSV23-unique† IPD 18.4 15.1 to 21.8 17.9 15.0 to 20.9 17.6 14.9 to 20.3
 NVT IPD 30.9 25.8 to 36.1 24.2 20.0 to 28.7 19.6 16.3 to 23.0
19–64 years
 All IPD 28.6 25.9 to 31.2 28.5 25.7 to 31.5 25.4 22.7 to 28.1
 PCV13* IPD 23.3 20.3 to 26.4 24.7 20.7 to 28.9 17.5 13.7 to 21.5
 PPSV23-unique† IPD 25.1 20.5 to 29.8 24.9 20.8 to 29.4 24.6 20.8 to 28.7
 NVT IPD 53.7 44.4 to 63.7 43.7 34.5 to 0.6 36.9 30.3 to 43.7
65 years or older
 All IPD 6.3 3.2 to 9.9 4.6 2.1 to 7.3 4.0 2.4 to 5.7
 PCV13* IPD 8.8 3.6 to 14.7 3.6 0.9 to 7.5 4.1 1.3 to 7.7
 PPSV23-unique† IPD 5.5 1.8 to 12.9 5.5 1.1 to 10.8 4.0 1.5 to 6.9
 NVT IPD 1.9 1.8 to 7.3 3.7 0.0 to 8.5 3.9 1.4 to 6.8
*Serotypes 1, 3, 4, 5, 6 A, 6B, 7F, 9V, 14, 18C, 19 A, 19F, 23F, and 6C.
†Serotypes 2, 8, 9N, 10A, 11A, 12F, 15B/C, 17F, 20, 22F, and 33F.

Serotype Distribution Pre-PCV13 and Post-PCV13 Introduction

From the 3 periods (2008–2009, 2011–2012, and 2017–2018), 89.6% of isolates had serotype information available. In PWH, PCV13 types contributed to 46.9% (228/486) of all IPD in 2008–2009 and declined to 21.5% (81/376) in 2017–2018 (see Table 3, Supplemental Digital Content, https://links.lww.com/QAI/B798). Serotype 19 A, a PCV13 type, was the most common serotype causing IPD among PWH in 2008–2009 (103/486, 21.2% of all IPD) but accounted for 4.5% (17/376) of IPD in 2017–2018 (P < 0.002) (Fig. 2A, see Table 3, Supplemental Digital Content, https://links.lww.com/QAI/B798). In 2017–2018, serotypes 9N (32/396, 8.5%) and 22F (28/376, 7.4%) were the most common serotypes overall and serotype 4 (23/376, 6.1%) was the most common PCV13-type IPD. Both the proportion (Fig. 2A) and the incidence (see Table 5, Supplemental Digital Content, https://links.lww.com/QAI/B798) of serotype 4 increased from baseline to 2017–2018, although the percent increase in incidence was not statistically significant (95.2%; 95% CI: −2.6 to 394.8). Of the 23 serotype 4 cases in 2017–2018, 91.3% were in adults aged 19–64 years, 91.3% occurred in California or Colorado, and 60.9% were in persons experiencing homelessness (see Table 6, Supplemental Digital Content, https://links.lww.com/QAI/B798).

F2
FIGURE 2.:
A, Distribution of invasive pneumococcal disease serotypes in adults aged 19 years or older with known HIV infection, 2008–2009 vs. 2017–2018. B, Distribution of invasive pneumococcal disease serotypes in adults aged 19 years or older without known HIV infection, 2008–2009 vs. 2017–2018. *P < 0.002. †Invasive pneumococcal disease cases due to serotypes 1, 5, and 14 were not detected. ‡Invasive pneumococcal disease cases due to serotype 2 were not detected.

In non-PWH, serotypes 7F (973/5292, 8.4%) and 19A (769/5292, 14.6%) were the most common serotypes in 2008–2009; in 2017–2018, they accounted for 1.5% (63/4242) and 2.9% (121/4242) of all IPD, respectively (P < 0.002). In 2017–2018, serotype 3 was the most common serotype (15.3%; 650/4242) causing IPD in non-PWH adults (Fig. 2B, and see Table 4, Supplemental Digital Content, https://links.lww.com/QAI/B798). From baseline to 2017–2018, serotype 3 IPD incidence increased by 15.5% (95% CI: 3.6 to 28.9). Serotype 4 incidence also increased, although much smaller compared with that observed in PWH (see Table 5, Supplemental Digital Content, https://links.lww.com/QAI/B798).

In PWH, PCV15-unique types and PCV20-unique types comprised 11.2% (42/376) and 17.0% (64/376) of IPD, respectively, in 2017–2018 (see Table 3, Supplemental Digital Content, https://links.lww.com/QAI/B798). These proportions were similar to those in non-PWH adults (PCV15-unique types: 584/4242, 13.8% and PCV20-unique types: 715/4, 242, 16.9%) (see Table 4, Supplemental Digital Content, https://links.lww.com/QAI/B798).

DISCUSSION

Dramatic reductions in IPD incidence were observed in both PWH and non-PWH in the United States after PCV13 introduction for children in 2010, primarily driven by the decline in PCV13-type IPD incidence. Despite these large declines, in 2017–2018, overall and PCV13-type IPD incidence among PWH was still approximately 17 and 13 times the incidence among non-PWH adults, respectively, with the highest overall IPD rates observed among PWH of non-Hispanic Black people both before and after PCV13 introduction. Among PWH and non-PWH, PCV13-type IPD incidence within each group was similar across race/ethnicity in 2017–2018 (see Table 2, Supplemental Digital Content, https://links.lww.com/QAI/B798), and the remaining difference in IPD incidence was primarily because of non-PCV13-type IPD.

Significant reductions in PCV13-type IPD incidence that occurred from 2008-2009 to 2011–2012 were due to indirect effects from PCV13 vaccination in children,23 and reductions observed from 2011-2012 to 2017–2018 reflect a combination of indirect PCV13 effects and potential effects from PCV13 use among adults with immunocompromising conditions including PWH or PCV13 use among adults aged 65 years or older. The decline of IRR of PCV13-type IPD in 2017–2018 compared with 2011–2012 in adults aged 19–64 years who currently do not have an age-based PCV13 recommendation may indicate that PWH benefited directly from PCV13 vaccination; however, the degree of impact of the direct PCV13 vaccination is unclear. Data on PCV13 coverage among PWH are limited. Analysis of medical claims data estimated that PCV13 coverage for PWH aged 18–64 years was 6.6% in October 2013 and had reached only 31.3% in December 2016 (IQVIA, anonymized patient-level data, December 2017; and Pfizer Inc, internal sales data for PCV13 2017, unpublished data). The National Health Interview Survey reported 20%–25% coverage of any pneumococcal vaccine in adults aged 19–64 years with indications for vaccination.24 In older adults for whom PPSV23 has been recommended since the 1980s, PPSV23 coverage among US Medicare beneficiaries aged 65 years or older with immunocompromising conditions has been around 50% in the past 10 years, whereas PCV13 coverage did not increase until 2015 after the age-based recommendation for PCV13 was introduced (CDC unpublished data). Given these estimates showing low pneumococcal vaccine coverage in this population, direct effects from vaccinating PWH was likely limited during our observation period.

Although the incidence of PCV13-type IPD among PWH declined for most serotypes, the exception was serotype 4, which increased. We previously reported that during 2010–2018, increase in serotype 4 IPD were observed within 3 of the 10 ABCs sites (CA, CO, and NM), most notable among persons experiencing homelessness.25 This is consistent with the serotype 4 cases observed in PWH in our study. Because serotype 4 is rarely detected in young children, the transmission reservoir is believed to exist in adults.26 In non-PWH, the incidence of both serotype 3 and serotype 4 increased, and serotype 3 was the most common IPD serotype in 2017–2018. Postlicensure data have shown varying estimates of PCV13 effectiveness against serotype 3 disease,27,28 and the minimal population-level impact of PCV13 against serotype 3 disease was observed in the United States in adults aged 65 years or older29 for whom routine PCV13 use was recommended, or in the United Kingdom, where routine PCV13 is not recommended routinely for adults.30 Therefore, improving vaccine coverage in high-risk populations such as persons experiencing homelessness may help reduce transmission of vaccine-type serotypes circulating among adults such as serotype 4; however, improved coverage by itself is unlikely to eliminate the remaining vaccine-preventable disease burden such as serotype 3 disease, which may require a more effective vaccine.

We observed reductions in NVT IPD incidence in PWH, which were not apparent among adults with other underlying conditions that are indications for PCV13 use.23 Factors other than PCV13 direct and indirect effects, such as improved access to HIV care,31 could have contributed to the decline in IPD incidence in PWH because highly active antiretroviral therapy has been associated with reduced risk of IPD.1,32 However, given that the reductions were not observed for PPSV23 unique serotypes and given the year-to-year variability in NVT incidence (Fig. 1), the decline in NVT incidence that we observed should be interpreted with caution because natural trends in individual serotypes and arbitrary selection of baseline against which NVT incidence changes are measured could overestimate or underestimate the measured effects.10

In the general population, IPD incidence increases with age, with highest incidence observed among older adults.23,33 In our analysis, IPD incidence among PWH aged 19–64 years was higher than those aged 65 years or older. In addition, non-Hispanic Black people had higher IPD rates compared with those of other race/ethnicity groups in both PWH and non-PWH. Younger adults and Black people with HIV infection are less likely to have sustained viral suppression compared with other age or race/ethnicity groups,34 and this may be contributing to the increased IPD rates in these groups. Increased IPD incidence in Black people compared with non-Black people has previously been reported, regardless of HIV status35–37; lower socioeconomic status38 and higher proportion of underlying conditions among Black people that increase the risk of IPD37,39 are believe to be the contributing factors. Introduction of PCV7 in children reduced racial disparities in all age groups because of the dramatic reduction of PCV7-type IPD.37 Our analysis demonstrates that disparities in PCV13-type IPD between non-Hispanic Black people and non-Hispanic White people with HIV were eliminated by 2017–2018, and most of the remaining differences in IPD incidence were due to non-PCV13 types.

Limitations

Our study is subject to several limitations. First, CDC's HIV surveillance data, which we used as denominators for IPD incidence in PWH, only capture diagnosed HIV cases. In 2008 and 2018, approximately 20% and 14% of PWH infection were estimated to not have had been diagnosed, respectively.40,41 Therefore, we could have overestimated IPD incidence in PWH, if patients with IPD (the numerator) were more likely to know their HIV status. Second, IPD cases with missing information on race/ethnicity were reclassified based on the distribution in cases with known race/ethnicity regardless of HIV status. Given the smaller proportion of non-Hispanic Black people among non-PWH, we could have underestimated incidence among non-Hispanic Black people with HIV, although the impact was likely small because <5% were missing race/ethnicity information in PWH. A larger proportion (12%–50%) of cases had missing data on ethnicity, and we likely underestimated IPD incidence among Hispanics in both PWH and non-PWH because the proportion of Hispanics among IPD cases in our study (6%–10%) was much smaller than the 18.5% that is estimated for the general US population42 or >20% among PWH.43 Third, we could not estimate IPD incidence for people with AIDS over time because ABCs data captured AIDS diagnosis at any point, whereas the HIV surveillance data captured persons with AIDS during a specified year, by residence at diagnosis. Fourth, ABCs does not capture vaccine coverage (for both PWH and non-PWH) or detailed information on HIV status, such as CD4 count at the time of illness or antiretroviral treatment history, which are known to affect IPD risk.44 Therefore, we were unable to assess the contribution of these factors to changes in IPD incidence over time or by age or race/ethnicity groups. Fifth, because our analysis is based on IPD data from 9 ABCs sites that are mostly urban,17 the findings may not be nationally representative. Finally, we were underpowered to assess changes in incidence rates among older adults and Hispanics with HIV.

Our study showed that introduction of PCV13 in the United States led to reduction in PCV13-type disease burden in both PWH and non-PWH and eliminated the disparity of PCV13-type IPD across race/ethnicity groups among PWH. However, PWH continue to be at increased risk of IPD, including PCV13-type IPD, compared with non-PWH. Although the 2012 recommendation may have had impact in reducing PCV13-type disease burden in PWH, the impact could have been limited, in part, because of low vaccine coverage among PWH. Higher-valency PCVs that were recently licensed for adults may help further reduce the disease burden among PWH and decrease racial disparities, along with efforts to ensure improved vaccine coverage in PWH to maximize vaccine benefits.

ACKNOWLEDGMENTS

The authors thank everyone in the Active Bacterial Core surveillance (ABCs) areas who was involved in the surveillance and maintenance of the system. The authors also thank the laboratorians and technicians who isolate the ABCs pathogens and make it possible to track these infections and the surveillance and laboratory personnel at the CDC for their careful work characterizing the isolates. The authors acknowledge the following members of the ABCs team and others for their contributions at the study sites: Susan Brooks, Pam Daily-Kirley, Maria Rosales, Joelle Nadle, and Katie Wymore (CA); Derek Evans, Carmen Marquez, and Daniel Wurm (CT); Wendy Baughman, Stephanie Thomas, and Amy Tunali (GA); Terresa Carter and Shannon Seopaul (MD); Brenda Jewell, Lori Triden, Megan Sulkulski, Kathy Como-Sabetti, Richard Danila, Ruth Lynfield, Paula Snippes, and Anita Glennen (MN); Kathy M. Angeles, Sarah A. Khanlian, Lisa Butler, Robert Mansmann, Emily Hancock, Karen Scherzinger, Gaby Keener, Joanne Keefe, S. Elizabeth Racz, Isaac Armistead, Chad Smelser, Salina Torres, Joseph Bareta, Brooke Doman, Megin Nichols, Chelsea McMullen, and Jeremy Espinoza (NM); Heather Jamieson and Tasha Martin (OR); and Tiffanie Markus, Brenda Barnes, and Katie Dyer (TN).

REFERENCES

1. Heffernan RT, Barrett NL, Gallagher KM, et al. Declining incidence of invasive Streptococcus pneumoniae infections among persons with AIDS in an era of highly active antiretroviral therapy, 1995–2000. J Infect Dis. 2005;191:2038–2045.
2. Flannery B, Heffernan RT, Harrison LH, et al. Changes in invasive pneumococcal disease among HIV-infected adults living in the era of childhood pneumococcal immunization. Ann Intern Med. 2006;144:1–9.
3. Cohen AL, Harrison LH, Farley MM, et al. Prevention of invasive pneumococcal disease among HIV-infected adults in the era of childhood pneumococcal immunization. AIDS. 2010;24:2253–2262.
4. Nabatanzi R, Bayigga L, Ssinabulya I, et al. Low antigen-specific CD4 T-cell immune responses despite normal absolute CD4 counts after long-term antiretroviral therapy an African cohort. Immunol Lett. 2014;162:264–272.
5. Abudulai LN, Fernandez S, Corscadden K, et al. Chronic HIV-1 infection induces B-cell dysfunction that is incompletely resolved by long-term antiretroviral therapy. J Acquir Immune Defic Syndr. 1999;71:381–389.
6. Emu B, Moretto WJ, Hoh R, et al. Composition and function of T cell subpopulations are slow to change despite effective antiretroviral treatment of HIV disease. PLoS One. 2014;9:e85613.
7. Nuorti JP, Whitney CG, Centers for Disease C, Prevention. Prevention of pneumococcal disease among infants and children—use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine - recommendations of the Advisory Committee on Immunization Practices (ACIP). Practice Guideline. MMWR Recomm Rep. 2010;59:1–18.
8. Centers for Disease Control & Prevention. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Practice Guideline. MMWR Morb Mortal Wkly Rep. 2010;59:1102–1106.
9. Centers for Disease Control & Prevention. Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children-advisory committee on immunization practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep. 2010;59:258–261.
10. Moore MR, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis. 2015;15:301–309.
11. Pilishvili T, Lexau C, Farley MM, et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 2010;201:32–41.
12. Whitney CG, Farley MM, Hadler J, et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003;348:1737–1746.
13. Lexau CA, Lynfield R, Danila R, et al. Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA. 2005;294:2043–2051.
14. Centers for Disease Control & 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;61:816–819.
15. Tomczyk S, Bennett NM, Stoecker C, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the advisory committee on immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2014;63:822–825.
16. Matanock A, Lee G, Gierke R, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 Years: updated recommendations of the advisory committee on immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:1069–1075.
17. Centers for Disease Control and Prevention. Surveillance Population. Available at: https://www.cdc.gov/abcs/methodology/surv-pop.html. Accessed August 25, 2020.
18. Langley G, Schaffner W, Farley MM, et al. Twenty years of active bacterial Core surveillance. Emerg Infect Dis. 2015;21:1520–1528.
19. Centers for Disease Control and Prevention. Methodology, 2018. Available at: https://www.cdc.gov/abcs/methodology/index.html. Accessed June 1, 2020.
20. Cooper D, Yu X, Sidhu M, et al. The 13-valent pneumococcal conjugate vaccine (PCV13) elicits cross-functional opsonophagocytic killing responses in humans to Streptococcus pneumoniae serotypes 6C and 7A. Vaccine. 2011;29:7207–7211.
21. U.S. Food & Drug Administration. July 16, 2021 Approval Letter- VAXNEUVANCE. Available at: https://www.fda.gov/media/150820/download. Accessed July 29, 2021.
22. U.S. Food & Drug Administration. June 10, 2021 Approval Letter-PREVNAR20; Available at: https://www.fda.gov/media/150021/download. Accessed July 29, 2021.
23. Ahmed SS, Pondo T, Xing W, et al. Early impact of 13-valent pneumococcal conjugate vaccine use on invasive pneumococcal disease among adults with and without underlying medical conditions-United States. Clin Infect Dis. 2019. doi: 10.1093/cid/ciz739.
24. Hung MC, Williams WW, Lu P-J, et al. Vaccination Coverage Among Adults in the United States, National Health Interview Survey; 2017. Available at: https://www.cdc.gov/vaccines/imz-managers/coverage/adultvaxview/pubs-resources/NHIS-2017.html. Accessed August 29, 2019.
25. Beall B, Walker H, Tran T, et al. Upsurge of conjugate vaccine serotype 4 invasive pneumococcal disease clusters among adults experiencing homelessness in California, Colorado, and New Mexico. J Infect Dis. 2021;223:1241–1249.
26. Metcalf BJ, Chochua S, Walker H, et al. Invasive pneumococcal strain distributions and isolate clusters associated with persons experiencing homelessness during 2018. Clin Infect Dis. 2021;72:e948–e956.
27. McLaughlin JM, Jiang Q, Gessner BD, et al. Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: a systematic review and pooled analysis. Vaccine. 2019;37:6310–6316.
28. Andrews N, Kent A, Amin-Chowdhury Z, et al. Effectiveness of the seven-valent and thirteen-valent pneumococcal conjugate vaccines in England: the indirect cohort design. Vaccine. 2019;37:4491–4498.
29. Pilishvili T, Gierke R, Farley M, et al. Epidemiology of Invasive Pneumococcal Disease (IPD) Following 18 Years of Pneumococcal Conjugate Vaccine (PCV) Use in the United States. Presented at IDWeek2020; October 21–25, 2020.
30. Ladhani SN, Collins S, Djennad A, et al. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000-17: a prospective national observational cohort study. Lancet Infect Dis. 2018;18:441–451.
31. Bradley H, Mattson CL, Beer L, et al. Increased antiretroviral therapy prescription and HIV viral suppression among persons receiving clinical care for HIV infection. AIDS. 2016;30:2117–2124.
32. Dworkin MS, Ward JW, Hanson DL, et al. Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination. Clin Infect Dis. 2001;32:794–800.
33. Centers for Disease Control and Prevention. ABCs Report: Streptococcous Pneumoniae; 2020. Available at: https://www.cdc.gov/abcs/reports-findings/survreports/spneu18.html. Accessed July 26, 2020.
34. Crepaz N, Dong X, Wang X, et al. Racial and ethnic disparities in sustained viral suppression and transmission risk potential among persons receiving HIV care—United States, 2014. MMWR Morb Mortal Wkly Rep. 2018;67:113–118.
35. Spicer JO, Thomas S, Holst A, et al. Socioeconomic and racial disparities of pediatric invasive pneumococcal disease after the introduction of the 7-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2014;33:158–164.
36. Barry P, Zetola N, Keruly J, et al. Invesive pneumococcal disease in a cohort of HIV-infected adults: incidence and risk factors, 1990–2003. AIDS. 2006;20:437–444.
37. Wortham JM, Zell ER, Pondo T, et al. Racial disparities in invasive Streptococcus pneumoniae infections, 1998-2009. Clin Infect Dis. 2014;58:1250–1257.
38. United States Census Bureau. Historical Poverty Tables: People and Families - 1959 to 2018. Available at: https://www.census.gov/data/tables/time-series/demo/income-poverty/historical-poverty-people.html. Accessed Aug 17, 2020.
39. Nowalk MP, Wateska AR, Lin CJ, et al. Racial disparities in adult pneumococcal vaccination indications and pneumococcal hospitalizations in the U.S. J Natl Med Assoc. 2019;111:540–545.
40. Centers for Disease Control and Prevention. HIV Surveillance Report; 2020. Available at: https://www.cdc.gov/hiv/statistics/overview/index.html#:∼:text=At%20the%20end%20of%202018,infections%20had%20not%20been%20diagnosed.&text=In%2050%20states%20and%20the%20District%20of%20Columbia.&text=CDC. Accessed July 14, 2020.
41. HIV surveillance—United States, 1981–2008. MMWR Morb Mortal Wkly Rep. 2011;60:689–693.
42. United States Census Bureau. Quick Facts United States. Available at: https://www.census.gov/quickfacts/fact/table/US/AGE775219. Accessed Aug 8, 2020.
43. Centers for Disease Control and Prevention. HIV Surveillance Report. vol. 31; 2018. Available at: http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Accessed December 28, 2020.
44. Feldman C, Anderson R, Rossouw T. HIV-related pneumococcal disease prevention in adults. Expert Rev Respir Med. 2017;11:181–199.
Keywords:

13-valent pneumococcal conjugate vaccine; invasive pneumococcal disease; indirect effects; direct effects; HIV infection

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