https://orcid.org/0000-0002-4113-4182
ABSTRACT
Annual influenza vaccination is recommended for all people living with HIV (PLWH), and so is pneumococcal vaccination at least once. This is due to higher incidence rates for both infections among PLWH, compared to HIV negative, even in the later highly active antiretroviral therapy era. To clarify the uptake of and attitude toward both vaccines among PLWH in Denmark, a survey on self-reported vaccine uptake was performed during 2017. Analyses identifying factors associated with vaccine uptake in the latest season for 203 participants were performed. Both influenza and pneumococcal vaccination uptake are low among PLWH in Denmark, 31.0% and 4.4%, respectively. Previous vaccination against influenza had the highest impact on influenza vaccine uptake, and lack of immunization guidance lowers the likelihood. Interventions to improve vaccination coverage are needed, such as increased awareness about guidelines and physician education.
Introduction
Immunization is a relatively easy and cheap medical prevention to reduce morbidity and mortality attributed to vaccine-preventable diseases in either healthy or immunocompromised people. People living with HIV (PLWH) have increased incidenceCitation1,Citation2 and mortalityCitation3 due to invasive pneumococcal disease (IPD), compared to the background population. Although the incidence has declined over the last 15–20 years,Citation4,Citation5 it remains significantly higher among PLWH, despite the use of highly active antiretroviral therapy.Citation6 Therefore, vaccination is recommended, as it is also the case against influenza. HIV infection is a risk factor for influenza-related complicationsCitation7,Citation8 and increases the risk of hospital admission due to influenza.Citation9 The prevalence of HIV in the Danish population is 0.1% with 75% being men. Guidelines for immunization of PLWH therefore recommend annual influenza vaccination, and for all adults, a single dose of 13-valent pneumococcal conjugate vaccine, which may be followed by a booster vaccination with the 23-valent pneumococcal polysaccharide vaccine.Citation10,Citation11 In Denmark, the influenza vaccine is free of charge for PLWH, whereas both pneumococcal vaccines have been with partial self-payment. However, since April 2020, the 23-valent pneumococcal polysaccharide vaccine has been made free of charge. Adherence to immunization guidelines can be difficult to evaluate, and there are not ample data either on vaccine uptake among PLWH or reasons for poor adherence. Factors influencing intentions to vaccinate can be assessed using the Health Belief Model.Citation12 For instance, in the general population; people are willing to be influenza vaccinated, if they believe that there is a high probability of contracting influenza, consider influenza a serious illness, deem the vaccine effective, and view vaccine side effects as minor.Citation13 In PLWH belief in the protection of the vaccine and influenza vaccination in the previous season are found to predict influenza vaccine uptake,Citation14 and reasons given for declining vaccination; did not think that they needed immunization and concerns about the adverse event.Citation15 Also, socio-demographics have been associated with a higher likelihood of vaccination in the general population, including female sex, increased educational attainment, and annual household income.Citation16 A person with a well-controlled HIV infection is more likely to be vaccinated.Citation17 Seasonal influenza vaccine uptake has been reported in the range 12–68%,Citation15,Citation18 and pneumococcal vaccine uptake in the range 3–79%,Citation19,Citation20 among PLWH in European countries. There is a great variation between countries and clinics. No Danish study has been conducted on the subject.
We hypothesized that Danish PLWH may be under-immunized. To investigate influenza and pneumococcal vaccine coverage and patients´ attitudes toward these vaccines, a questionnaire study was conducted among PLWH. Finally, the study aimed to identify predictors for vaccine uptake.
Materials and methods
This is a cross-sectional survey based on self-reported vaccine uptake against influenza and pneumococcal disease reported by the use of a questionnaire. The study participants were PLWH, ≥18 years, and treated at Odense University Hospital, Denmark. Odense University hospital is a tertiary hospital serving a population of 1.2 million people in the Region of Southern Denmark, including all PLWH in the region. The participants were included consecutively from April 2017 to September 2017 during their scheduled visit to the outpatient HIV clinic. Five hundred and eighty HIV-positive patients were followed at the clinic in 2017, and 469 had an appearance at the clinic in the inclusion period. The response rate cannot be calculated as the number of questionnaires distributed was not registered. Patients who were unable to understand Danish or English were excluded from study participation. Paper questionnaires were primarily completed by the participants alone. When necessary, a nurse could help to clarify the questions.
The data were entered into an electronic database by the study investigator by double entry. Data are stored in a secure web-based electronic data capture tool (REDCap) hosted at the Region of Southern Denmark.
Variables
The questionnaire consisted of four parts:
(1) Demography including sex, age, race, educational level, and annual household income in the last year (all fixed answers).
(2) Known allergies (fixed answers and two free text). Influenza vaccine uptake the latest season (defined as vaccination from October to February the latest winter), influenza vaccine uptake any prior season, and intention to have the influenza vaccination next season (both fixed answers). Reasons for not being influenza vaccinated the latest season (fixed answers and one free text).
(3) Pneumococcal vaccine offered ever and uptake (both fixed answers), why and who recommended, if they were vaccinated, including year, name of vaccine (free text), and reasons for not being vaccinated (fixed answers and one free text).
(4) Primary information source recommending immunization (fixed answers and one free text).
In most questions, the participants also had the possibility to fill in ´Don’t know´ or ´Don’t want to disclose´.
A copy of the questionnaire is added as supplement material.
Ethics
Participation in the survey was voluntary. The survey was approved by the National Data Protection Agency (no. 16/26770) and was conducted in accordance with the Helsinki Declaration.
Statistical analysis
Descriptive statistics were calculated for baseline characteristics for the study population. For continuous variables, the median and interquartile range (IQR) were reported. For dichotomous and categorical variables the number and percentage of patients were listed, relative to the total number of patients, for whom information was available about the characteristic under investigation. Correlations with influenza vaccine uptake in the latest season and the factors; age group, sex, educational level, household income, information source, and any prior influenza vaccination were analyzed using univariable logistic regression. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. A cutoff of p-value <0.1 was used to determine which variables to include in the multivariable logistic regression analysis. Margins plot was made to estimate, whether an interaction term was to be included. A two-tailed p-value ≤0.05 was considered statistically significant. All analyses were performed using Stata version 15 (StataCorp, College Station, TX, USA). If a question was not filled in (No data), or answered ´Don’t know´, or ´Don’t want to disclose´ it was reported as such, when the baseline characteristics were reported.
Results
A total of 203 PLWH consented to participate in the survey. No questionnaires were excluded. The overall median age of the study population was 51 years (IQR 42–59), 146 (71.9%) participants were men, and 167 (82.3%) Caucasians. The baseline characteristics for the study population are summarized in .
Table 1. Demographics and socioeconomic characteristics for all 203 people living with HIV
Influenza vaccine coverage in the latest season was 31.0% (63 participants), and influenza vaccine uptake any other season, apart from the previous, was 42.9% (87 participants). Of the 137 participants, who were not influenza vaccinated in the latest season, the three most frequently reported reasons for not receiving influenza vaccination were perception of good health with no need for vaccination (38.7%)(reported as free text), was not informed that the vaccine was recommended (25.6%), and concern about side effects (11.0%). Pneumococcal vaccination had been offered to 13 (6.4%) participants, and pneumococcal vaccine uptake was overall 4.4% (9 participants). HIV infection was reported as the main reason for being offered a pneumococcal vaccine (30.8%) and was primarily recommended by an infectious disease specialist (38.5%). Only one participant could report getting a 13-valent pneumococcal conjugate vaccine. The information source recommending immunization was most often the infectious disease specialist 28.1% (57 participants), followed by general practitioner 23.2% (47 participants). Sixty participants (29.6%) had not been informed about immunization, and 12 participants (5.9%) did not answer the question. Of these 72 participants, 7 were influenza vaccinated in the latest season, and none pneumococcal vaccinated. No participants reported an allergy contraindicating vaccination. The vaccination questionnaire answers are summarized in .
Table 2. Influenza and pneumococcal vaccination uptake and source of information regarding immunization of 203 people living with HIV
Factors associated with influenza vaccination in the latest influenza season
In univariable analysis, a history of any prior influenza vaccination was the strongest predictor for receiving an influenza vaccination in the latest season (OR 10.34, 95% CI 4.75–22.52) (p < .001), compared to never having been influenza vaccinated (). Age ≥60 years was a predictor for receiving an influenza vaccination in the latest season (OR 4.12, 95% CI 1.93–8.80) (p < .001), compared to age <50 years. A factor that reduced the probability of receiving the influenza vaccine was no advice given (OR 0.10, 95% CI 0.03–0.27) (p < .001), compared to advice given by a general practitioner, but also significantly different to the other information sources. Due to the small numbers in strata, this factor was not included in the multivariable analysis. The remaining factors were not associated with influenza vaccination. Thus, age groups and any prior influenza vaccination were then included in multivariable analysis, with an interaction term due to interaction (R2 = 0.229). Influenza vaccination any prior season was significantly associated with receiving influenza vaccination in the latest season (OR 4.13, 95% CI 1.20–14.21) (p = .025), and age was not.
Table 3. Factors associated with influenza vaccine uptake in the latest season in univariable and multivariable logistic regression among people living with HIV
Due to the limited number of participants who received a pneumococcal vaccine, it was not possible to perform univariable or multivariable analyses of predictors of pneumococcal vaccination in this population.
Discussion
In this first Danish study assessing influenza and pneumococcal vaccine uptake in PLWH, influenza vaccine uptake in the latest season was 31%, and the main predictor for vaccine uptake was any prior influenza vaccination. Pneumococcal vaccine uptake was even lower only 4.4%, and only 6.4% had been offered. The main reasons for not being vaccinated were lack of immunization guidance and perception of not needing vaccination.
This low influenza vaccine uptake is greatly below the ECDC target of 75% vaccination coverage for vulnerable patients,Citation21 but comparable to other European studies that have reported influenza vaccine uptake among PLWH to be in the range of 11.9–68%.Citation15,Citation18–20,Citation22,Citation23 In comparison, 5% of the Danish background population between 15 and 64 years, were vaccinated in the 2016/17 season and 47% of those older than 64 years.Citation24 A study by Althoff et al.Citation14 also established that influenza vaccination in the previous season to be a strong predictor of influenza vaccination in the next season, among women with HIV in the USA. So if people are introduced to immunization, have used it, there is a high probability they will continue using it. In our cohort, 29.6% of the participants reported that they had not received any immunization counseling, and with univariable analysis, this was a negative predictor for influenza vaccine uptake, compared to any recommendation given. This indicates that lack of information and guidance regarding immunization may be partly the reason for suboptimal vaccine uptake. Harrison et al.Citation18 reported that a recommendation from the general practitioner or infectious disease specialist increased the probability of vaccination 13 times in PLWH.
Reasons for declining influenza vaccination were the participants´ perception of their own good health with no need for vaccination and concern about side effects. These findings are overall in line with a British study,Citation15 which reported that 25% of participants refused vaccination due to perception of good health and 23% because of concerns about side effects. Harrison et al.Citation18 also reported fear for side effects and not considering influenza a severe disease as main reasons for declining influenza vaccination, among PLWH, and in addition, fear of exacerbation of HIV due to vaccination. None of the participants mentioned the latter in our study by free text.
Pneumococcal vaccine coverage was very low in our cohort, despite the fact that it is recommended by the international guidelinesCitation10,Citation11 and the Danish Health Authority.Citation25 Only one European study, a French single-center study from 2007,Citation19 has reported an equivalent vaccine uptake of 3.3% among PLWH. Other European studies have reported pneumococcal vaccine coverage in the range 26.4–79% for PLWH.Citation20,Citation22,Citation23,Citation26–28 This low uptake may be a consequence of multiple factors, such as the pneumococcal vaccine not being free of charge for the patients at the time of this study, and no overall national campaign for pneumococcal vaccinations has been made in Denmark, contrary to influenza vaccination. Awareness of vaccination in both the patients and treating physicians may therefore be low. Traditionally, general practitioners are responsible for vaccinations at the patient’s own request in Denmark. In our cohort, infectious disease specialists were the primary information source recommending immunization. This may be a result of PLWH rarely visiting their general practitioner but attend a HIV clinic minimum once or twice a year, or the general practitioner may be unaware of their HIV status.
Vaccination recommendations are also likely to vary across different physicians at the same health care facility, as shown by Cotte et al. and Lim et al.Citation29,Citation30 A study done in South Africa showed that self-reported influenza vaccine uptake among health care workers, awareness of the guidelines, and influenza training were associated with a higher likelihood of recommending influenza vaccination to PLWH in their care.Citation31 This supports that there should be increased awareness of the immunization programs at HIV clinics, education for health care personnel working with PLWH, and a formalization of how immunization recommendations are given.
The current data has provided additional evidence to the literature, showing that PLWH still are not sufficiently informed about the opportunity and the benefits of vaccination, although recommended for years in guidelines. This study also contributes with the knowledge, that in a country with equal and free access to the health care system for all citizens, it does not seem that socio-demographic factors make a difference for influenza vaccination in PLWH.
Further studies are needed in order to investigate whether or not the new Danish Health Authority recommendation and removal of the patient-fee for the 23-valent pneumococcal polysaccharide vaccine will increase vaccine uptake. Additionally, studies evaluating HIV physicians´ awareness of immunization guidance and how this is provided are necessary. This study clarifies that immunization is not prioritized among PLWH and immunization counseling needs to be optimized to improve vaccine uptake amongst PLWH.
Limitations of this study include the following: It is a single-center study with data from a single season. Our population may differ from other populations. Data collection was anonymous, and self-reported immunization rates could not be confirmed with hospital records. PLWH, who declined to participate in the study, might have had a lower rate of vaccine uptake resulting in an overestimation in our reported uptake levels. Unanswered questions also limit the accuracy of the data. Finally, our cohort only includes PLWH who are in outpatient treatment and able to understand Danish or English.
Conclusion
Both Influenza and pneumococcal vaccination uptake are low among PLWH in Denmark. Previous influenza vaccination had the highest impact on vaccination behavior, and lack of information about vaccination lowers the likelihood of vaccine uptake. Interventions to improve vaccination coverage are needed, and increased awareness about guidelines and physician education is warranted.
Supplemental Material
Download MS Word (14.7 KB)Disclosure of potential conflicts of interest
None of the authors had conflicts of interest.
Supplemental data
Supplemental data for this article can be accessed on the publisher’s website.
Additional information
Funding
References
- Backhaus E, Berg S, Andersson R, Ockborn G, Malmstrom P, Dahl M, Nasic S, Trollfors B. Epidemiology of invasive pneumococcal infections: manifestations, incidence and case fatality rate correlated to age, gender and risk factors. BMC Infect Dis. 2016;16:367
- Klemets P, Lyytikainen O, Ruutu P, Ollgren J, Nuorti JP. Invasive pneumococcal infections among persons with and without underlying medical conditions: implications for prevention strategies. BMC Infect Dis. 2008;8:96.
- Giner AM, Kuster SP, Zbinden R, Ruef C, Ledergerber B, Weber R. Initial management of and outcome in patients with pneumococcal bacteremia: a retrospective study at a Swiss university hospital, 2003-2009. Infection. 2011;39:519–26.
- Sadlier C, O’Connell S, Kelleher M, Bergin C. Incidence and risk factors for invasive pneumococcal disease in HIV-positive individuals in the era of highly active antiretroviral therapy. Int J STD AIDS. 2019;30:472–78.
- Marcus JL, Baxter R, Leyden WA, Muthulingam D, Yee A, Horberg MA, Klein DB, Towner WJ, Chao CR, Quesenberry CP. Invasive pneumococcal disease among HIV-infected and HIV-uninfected adults in a large integrated healthcare system. AIDS Patient Care STDS. 2016;30:463–70
- Harboe ZB, Larsen MV, Ladelund S, Kronborg G, Konradsen HB, Gerstoft J, Larsen CS, Pedersen C, Pedersen G, Obel N, et al. Incidence and risk factors for invasive pneumococcal disease in HIV-infected and non-HIV-infected individuals before and after the introduction of combination antiretroviral therapy: persistent high risk among HIV-infected injecting drug users. Clin Infect Dis. 2014;59:1168–76
- Ho A, Mallewa J, Peterson I, SanJoaquin M, Garg S, Bar-Zeev N, Menyere M, Alaerts M, Mapurisa G, Chilombe M, et al. Epidemiology of severe acute respiratory illness and risk factors for influenza infection and clinical severity among adults in Malawi, 2011–2013. Am J Trop Med Hyg. 2018;99: 772–79
- Tempia S, Walaza S, Moyes J, Cohen AL, von Mollendorf C, Treurnicht FK, Venter M, Pretorius M, Hellferscee O, Mtshali S, et al. Risk factors for influenza-associated severe acute respiratory illness hospitalization in South Africa, 2012-2015. Open Forum Infect Dis. 2017;4:262
- Peters PJ, Skarbinski J, Louie JK, Jain S, Roland M, Jani SG, Finelli L, Brooks JT. HIV-infected hospitalized patients with 2009 pandemic influenza A (pH1N1)–United States, spring and summer 2009. Clin Infect Dis. 2011;52(Suppl 1):S183–8
- Geretti AM, Brook G, Cameron C, Chadwick D, French N, Heyderman R, Ho A, Hunter M, Ladhani S, Lawton M, et al. British HIV association guidelines on the use of vaccines in HIV-positive adults 2015. HIV Med. 2016;17(Suppl 3):s2–s81
- Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:e44–100
- Rosenstock IM. Why people use health services. Milbank Mem Fund Q. 1966;44:94–127.
- Tsutsui Y, Benzion U, Shahrabani S, Din GY. A policy to promote influenza vaccination: a behavioral economic approach. Health Policy (New York). 2010;97:238–49.
- Althoff KN, Anastos K, Nelson KE, Celentano DD, Sharp GB, Greenblatt RM, French AL, Diamond DJ, Holman S, Young M, et al. Predictors of reported influenza vaccination in HIV-infected women in the United States, 2006-2007 and 2007-2008 seasons. Prev Med. 2010;50:223–29
- Ellis J, Brown J, Smith C, Snell L, Capocci S, Ferro F, Ferreira J, Marshall N, Webster D, Johnson M, et al. Influenza immunisation: knowledge and actions taken by UK HIV-positive adults. HIV Med. 2016;17:397–99
- La EM, Trantham L, Kurosky SK, Odom D, Aris E, Hogea C. An analysis of factors associated with influenza, pneumoccocal, Tdap, and herpes zoster vaccine uptake in the US adult population and corresponding inter-state variability. Hum Vaccin Immunother. 2018;14:430–41.
- Gallagher KM, Juhasz M, Harris NS, Teshale EH. Predictors of influenza vaccination in HIV-infected patients in the United States, 1990-2002. J Infect Dis. 2007;196:339–46.
- Harrison N, Poeppl W, Herkner H, Tillhof KD, Grabmeier-Pfistershammer K, Rieger A, Forstner C, Burgmann H, Lagler H. Predictors for and coverage of influenza vaccination among HIV-positive patients: a cross-sectional survey. HIV Med. 2017;18:500–06
- Mohseni-Zadeh M, Rey D, Batard ML, Beck Wirth G, Partisani ML, Lang JM, Hansmann Y, Christmann D, Martinot M. Inadequate vaccination coverage in a French cohort of HIV positive patients. Med Mal Infect. 2010;40:683–90
- Tsachouridou O, Georgiou A, Naoum S, Vasdeki D, Papagianni M, Kotoreni G, Forozidou E, Tsoukra P, Gogou C, Chatzidimitriou D, et al. Factors associated with poor adherence to vaccination against hepatitis viruses, streptococcus pneumoniae and seasonal influenza in HIV-infected adults. Hum Vaccin Immunother. 2019;15:295–304
- ECDC. Seasonal influenza vaccination and antiviral use in EU/EEA Member States [accessed 17 Aug. 2020]. https://www.ecdc.europa.eu/sites/default/files/documents/seasonal-influenza-antiviral-use-2018.pdf.
- Boey L, Bosmans E, Ferreira LB, Heyvaert N, Nelen M, Smans L, Tuerlinckx H, Roelants M, Claes K, Derdelinckx I, et al. Vaccination coverage of recommended vaccines and determinants of vaccination in at-risk groups. Hum Vaccin Immunother. 2020;16;2136–2143
- Valour F, Cotte L, Voirin N, Godinot M, Ader F, Ferry T, Vanhems P, Chidiac C. Vaccination coverage against hepatitis A and B viruses, streptococcus pneumoniae, seasonal flu, and A(H1N1)2009 pandemic influenza in HIV-infected patients. Vaccine. 2014;32:4558–64
- Statens serum institut. Influenza. Vaccinationstilslutning. 2020 [accessed 17 Aug, 2020]. https://statistik.ssi.dk//sygdomsdata#!/?vaccination=14&sex=3&agegroup=10&landsdel=100&xaxis=Season&show=Graph&season=2016%7C2016&datatype=Vaccination.
- Statens Serum Institut. Pneumokokvaccination uden for børnevaccinationsprogrammet i Danmark. 2020, [accessed 17 Aug, 2020]. https://www.ssi.dk/-/media/arkiv/dk/vaccination/risikogrupper/rapport-vedr-pneumokokvacc-udenfor-boernevaccprogram-14042020.pdf?la=da.
- Molloy A, Curtis H, Burns F, Freedman A. Routine monitoring and assessment of adults living with HIV: results of the British HIV Association (BHIVA) national audit 2015. BMC Infect Dis. 2017;17:619.
- Quinn KJ, McCarty EJ, Quah SP, Emerson CR, Donnelly CM. Managing vaccines: defining the remit of primary care and specialist HIV clinics in the delivery of immunization to individuals with HIV infection. Int J STD AIDS. 2012;23:136–37.
- Vivancos-Gallego MJ, Muriel A, Serrano-Villar S, Moreno-Zamora A, Pérez-Elías MJ, Quereda C, Casado JL, Sánchez-Conde M, Del Campo S, Dronda F, et al. Pneumococcal vaccination in adult people living with HIV on suppressive antiretroviral therapy: a case-control study. Int J STD AIDS. 2020;31:174–82
- Cotte L, Voirin N, Richard C, Brochier C, Schlienger I, Lack P, Lina B, Vanhems P, Zoulim F. Factors associated with pandemic influenza A/H1N1 vaccine coverage in a French cohort of HIV-infected patients. Vaccine. 2011;29: 5638–44
- Lim PL, Tan J, Yusoff Y, Win MK, Chow A. Rates and predictors for influenza vaccine prescriptions among HIV-infected clinic patients in Singapore. Ann Acad Med Singapore. 2013;42:173–77.
- Duque J, Gaga S, Clark D, Muller M, Kuwane B, Cohen C, Walaza S, Tempia S, Ramatoboe P, Furumele T, et al. Knowledge, attitudes and practices of South African healthcare workers regarding the prevention and treatment of influenza among HIV-infected individuals. PloS One. 2017;12:e0173983