COVID-19 Vaccine Hesitancy among French People Living with HIV

People living with HIV are a high-risk population concerning the coronavirus 19 (COVID-19) infection, with a poorer prognosis. It is important to achieve high COVID-19 vaccination coverage rates in this group as soon as possible. This project used self-reporting to assess vaccine hesitancy and acceptance among people living with HIV towards the novel COVID-19 vaccine. Sixty-eight (28.7%) participants among the 237 declared their hesitancy to be vaccinated against COVID-19. Participants who expressed concerns about their health (p < 0.001), the requirement of mandatory COVID-19 vaccination (p = 0.017), and their chronic disease status (p = 0.026) were independently associated with the acceptance of vaccination. Conversely, participants presenting general vaccine refusal (p < 0.001), concerns about the serious side effects of COVID-19 vaccines (p < 0.001), and those already thinking having an immune status to COVID-19 (p = 0.008) were independently associated with COVID-19 vaccine hesitancy. Our results suggest that vaccine strategy would be more successful in France with a communication strategy emphasizing the collective benefits of herd immunity in the population living with HIV and reassuring patients with chronic diseases about the safety of the proposed vaccines.


Introduction
The coronavirus 19  pandemic has exerted a heavy toll in terms of the burden of disease and deaths worldwide, with dozens of candidate vaccines against COVID-19 in development. As of February 2021, three COVID-19 vaccines with greater than 90% efficacy to reduce symptomatic infection risk [1,2] have been approved in the European Union, and 15 potential vaccines are in phase 3 trials [3]. Nevertheless, COVID-19 vaccine hesitancy might represent a major hurdle to achieving herd immunity [4][5][6][7].
A major portion of the people who refused to be vaccinated report being worried about the safety of the new COVID-19 vaccines [8,20]. Popular media has brought to attention a constant problem plaguing the French population health in recent years: vaccine hesitancy. Antivax group statements, conspiracy theories, myths and misperceptions, questions about the speed of vaccine development and long-term side effects, and expert opinion on challenges with the COVID-19 vaccine have been proliferating in the French media. Nevertheless, recent studies have relativized the role of these groups in vaccine hesitancy [21,22]. The scientific community and public health experts expressed concerns as early as the summer of 2020 about vaccine hesitancy in the European Union [23], in addition to the challenges associated with costs, access, effectiveness, and the logistics of vaccine deployment [24][25][26].
Vaccine hesitancy is not a novel phenomenon in France and worldwide. Before the COVID-19 pandemic, the World Health Organization mentioned vaccine hesitancy as one of the top global health threats [27]. While there is considerable enthusiasm and anticipation for the COVID-19 vaccine, little is known about vaccine hesitancy, especially for COVID-19, in vulnerable French populations. A vulnerable population, as people living with HIV, presents poorer COVID-related outcomes compared to those without HIV [28][29][30]. Currently, little evidence exists on how HIV infection affects the risk of poor outcomes from COVID-19 [31]. However, persons living with HIV are more hospitalized and present with a higher mortality risk than persons without diagnosed HIV [29,32]. A large population-based cohort in South Africa showed the COVID-19 mortality risk among people living with HIV to be double the risk of those without HIV [33]. In addition, in Spain, HIV-infected patients with COVID-19 presented a higher prevalence of critical illnesses compared to those without HIV [34]. In the UK, HIV patients had a higher risk of COVID-19 death than those without HIV [35]. These findings present that people living with HIV might be a high-risk group for COVID-19 deaths, indicating an urgent need to consider targeted policies and vaccinal campaigns for this group. People living with HIV may need priority consideration for COVID-19 vaccination. Thus, it is essential to understand the possible reasons for refusing a COVID-19 vaccine to better respond to their worries or hesitancies. This study focuses on COVID-19 vaccine hesitancy and its determinants in a French population of people living with HIV.

Materials and Methods
This study was conducted in January 2021 with people living with HIV followed up on for this diagnosis in Foch Hospital, Suresnes, France. In our HIV clinic, 690 patients were followed up on, and 527 of them gave their e-mail addresses. The mean duration of HIV infection is 18 years, mean age: 53 years old; 98% of those infected are receiving antiretroviral therapy, and in 95% of these cases, the HIV viral load is undetectable during treatment. These patients have twice-yearly outpatient visits. Participants with no idea about either vaccine acceptance or vaccine hesitancy were excluded from the analysis.
An anonymous online survey was developed based on past research involving attitudes and behaviors about vaccinations [36,37]. The survey assessed: -the demographic characteristics of participants, -general attitudes and perceptions of vaccines, -COVID-19-personal opinions, -Personal views-COVID-19 and vaccines, and -Personal experiences with COVID-19. According to the WHO Strategic Advisory Group of Experts on Immunization, vaccine hesitancy was defined as "delay in acceptance or refusal of vaccine despite availability of vaccination services" [38].
This study was approved by Foch IRB: IRB00012437 (approval number: 21-01-12) on 15 March 2021. Willing consent was obtained for all participants.

Statistical Analysis
We computed descriptive statistics to describe the demographic characteristics of the study participants. Pearson's chi-square test was used to identify significant differences between participants who would accept and be hesitant regarding the COVID-19 vaccine. The responses were compared by dichotomizing the variable as a positive (yes) or hesitant attitude (no or not for the moment) towards a COVID-19 vaccine, indicating the extent of vaccine hesitancy. Multiple backward logistic regression was performed to identify the predictors of COVID-19 vaccine acceptance. Statistical significance was established at an alpha of p < 0.05. Data were analyzed using SAS software (version 9.4; SAS Institute, Cary, NC, USA).

Results
The survey was completed by 237 of the 527 patients living with HIV (response rate = 45.0%).
The sample was 22% female, and 69% of participants were aged between 45 to 64 years (Table 1). Sixty-eight (28.7%) participants among the 237 declared their hesitancy to be vaccinated against COVID-19.
Most (73.7%) of the participants declared that they have been confronted with COVID-19 through a personally known person and 24% through the death of one. Only 10% of the participants declared that they had been infected by COVID-19. The hesitancy towards vaccines in general was very low, only 5% of the study population, and only 7% thought that the French population received too many vaccines. Some (37.1%) of the participants had concerns about COVID-19 vaccines. However, among those with knowledge of mRNA vaccines, only 17.8% reported this fear.
In the multiple logistic regression, six different items (items 5, 8, 12, 14, 18, and 22 of Table 1) were predictive of COVID-19 vaccination hesitancy. Item 8, which expressed concerns about health (p < 0.001), item 12 for mandatory COVID-19 vaccination (p = 0.017), and item 14 that vaccination was important for patients with chronic disease (p = 0.026) were significantly associated with the acceptance of vaccination. Conversely, item 5 showing a general vaccine refusal (p < 0.001), item 18 with concerns about the serious side effects of COVID-19 vaccines (p < 0.001), and item 22 with already thinking that an immune status to COVID-19 (p = 0.008) was significantly associated with COVID-19 vaccination hesitancy.

Discussion
Sixty-eight of the participants were hesitant to be vaccinated. This indicates that, in our sample, around three out of 10 people living with HIV were vaccine-hesitant, despite having a self-perception of elevated risk of exposure to COVID-19 infection.
A previous study showed that 29% of the French working-age population would refuse any COVID-19 vaccine, 27% would accept COVID-19 vaccines provided in mass vaccination centers, even with less favorable characteristics (vaccine efficacy at 50% and risk of serious side effects at one in 10000) and a manufacturer based in China, and 43% would remain hesitant unless COVID-19 vaccines had better characteristics or were manufactured in the USA or EU [9]. Age was not associated with COVID-19 vaccine hesitancy in our specific population of people living with HIV. However, a recent French study, focused on the working-age population, showed that vaccine hesitancy and vaccination refusal were associated with age with an inverted U-shaped relationship [9]. Other French studies showed that vaccine refusal and vaccine hesitancy were independent of age in specific populations, such as medical practitioners [10,39].
We found that anti-COVID-19 vaccination behavior was strongly associated with certain characteristics of the participants: fear about COVID-19 infection and health, willingness to make COVID-19 vaccination mandatory, and being a patient with a chronic disease were factors associated with a willingness to be vaccinated. Conversely, general doubts about vaccination, a fear of serious side effects from COVID-19 vaccines, and feeling already immune were factors associated with a hesitancy to be vaccinated. These results corroborate with other studies' findings on the determinants of COVID-19 vaccine hesitancy [8,40,41], especially the distrust in vaccination and vaccine hesitancy [42]. Vaccine concerns have been reported due to the newness of the COVID-19 vaccines [8,43,44]. The main cited reasons for vaccination hesitancy were a fear of side effects, safety, and effectiveness [8,45]. Moreover, other reported reasons for vaccine refusals were the unnecessity of vaccination, inadequate information, unknown/short duration of immunity, and a general antivaccine stand [8,46].
Even if gender remained nonpredictive of a willingness to get a COVID-19 vaccination, in our population, women were more likely to refuse a COVID-19 vaccine. Indeed, men are more receptive to COVID-19 vaccines and more inclined to accept pharmaceutical interventions [47] such as vaccinations [48].
Moreover, as observed with other studies on COVID-19 vaccination intentions, we found that a general vaccine refusal could fuel anti-COVID-19 vaccination behaviors [9,10,49]. Outright vaccine refusal was highly correlated with a lower perceived severity of COVID-19 if infected [9]. Thus, for these patients, the individual benefit-risk assessment of COVID-19 vaccination could be perceived unfavorable [50].
Hesitancy is diminished with stronger vaccine efficacies and a lower risk of serious adverse effects and increased if the vaccination is only accessible in mass vaccination centers rather than a GP practice or local pharmacy [51]. The recommendation of vaccination by a GP was not enough to compensate for COVID-19 vaccine hesitancy related to mass vaccination centers [51]. Moreover, communication on the collective herd immunity in terms of a herd immunity target leads to significantly reduced COVID-19 hesitancy [9,52].
Our results of people living with HIV could be compared to a healthy population. Schwarzinger et al. showed that, among 1942 adults aged 18-64 years residing in France with no history of COVID-19, participants who never complied with recommended vaccinations in the past were more likely to refuse any COVID-19 vaccine [9]. Participants who perceived COVID-19 as a very severe disease were less likely to refuse any COVID-19 vaccine [9]. Moreover, vaccine hesitancy decreases with communication about the collective benefits of herd immunity, but GP advice on vaccinations was not associated with vaccine hesitancy [9]. Thus, we observed that, generally, the same items were collected among the general population and our specific population. However, the general population vaccine hesitancy was dependent on age, gender, and socioeconomic status [9,10]. These are the main differences to our results, showing no effect on age and gender toward COVID-19 vaccine hesitancy. This could be explained by the particular aspect of the HIV disease showing the importance of care regardless of age because of its chronic aspect. Gender was significant in the univariate analysis but did not remain significant in the multiple regression; this could be explained by the low proportion of women in our study (less than 24% in the overall population). The absence of socioeconomic information remains the main limitation of our study, which does not allow us to compare to other findings. The general population showed distrust in vaccinations and vaccination complacency as possible exacerbating attitudes for anti-COVID-19 vaccination behaviors [42]. Moreover, vaccination hesitancy is generally associated with a lower compliance with immunization, reflecting the anchoring effect of negative attitudes toward vaccinations in France [15,51,53].

What This Study Adds
This study is the first to evaluate vaccine hesitancy among patients living with HIV towards COVID-19 vaccination. Understanding HIV patients' perspectives is important as health systems begin planning vaccination rollouts for the COVID-19 vaccines, especially in chronic disease patients.

Limitations of This Study
The limitations of this study include a relatively low response rate (45.0%) and data collection at a single medical hospital, which may impact the generalizability. Our study was internet-based; thus, we could not eliminate the selectivity bias. Our study was a cross-sectional study, so no causality could be established. The questionnaire was designed to be simple and easy-to-answer, so we could not evaluate daily habits. The French ethical aspects of our anonymous questionnaire did not allow us to question the participants about their socioeconomic and educational statuses. This did not allow us to compare our results to the literature focused on these topics. The respondents could also have been predominantly influenced by exposure to COVID-19 vaccine-related topics in the media; no information on the time of exposure to the media or other media information and propaganda from public institutions about the spread of COVID-19 vaccines were collected during the online questionnaire.

Conclusions
The majority of this cohort had positive attitudes regarding COVID-19 vaccinations, comparable to prior studies [9,26,39]. Despite the limitations, this study shed light on the COVID-19 vaccine hesitancy among participants living with HIV. Our results suggest that a vaccine strategy would be more successful in France with a communication strategy, emphasizing the collective benefits of herd immunity in the population living with HIV and reassuring patients with the chronic disease about the safety of the proposed vaccines.

Institutional Review Board Statement:
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Informed Consent Statement:
A non-opposed consent was obtained for patients.

Data Availability Statement:
No new data were created or analyzed in this study.