key: cord-0725771-2fj184z3
authors: Milano, Eugenio; Ricciardi, Aurelia; Casciaro, Raffaella; Pallara, Elisabetta; De Vita, Elda; Bavaro, Davide F.; Larocca, Angela Maria Vittoria; Stefanizzi, Pasquale; Tafuri, Silvio; Saracino, Annalisa
title: Immunogenicity and safety of the BNT162b2 COVID‐19 mRNA vaccine in PLWH: A monocentric study in Bari, Italy
date: 2022-02-08
journal: J Med Virol
DOI: 10.1002/jmv.27629
sha: e248ea88c0a46b749dcc1484785261ca8cafed82
doc_id: 725771
cord_uid: 2fj184z3

In March, people living with HIV infection (PLWH) were included in the risk category of fragile people for severe COVID‐19 receiving priority access to vaccination with BNT162b2 vaccine. The aim of the study was to evaluate the immunogenicity and safety of the two doses regimen. The antibodies titer for severe acute respiratory syndrome‐related coronavirus‐2 (SARS‐CoV‐2) was evaluated after 21 days since the first administration (Time 1), 1 (Time 2), and 3 (Time 3) months post‐vaccination. Information regarding virological and immunological conditions at baseline, previous SARS‐CoV‐2 state of infection, other immunodeficiencies, current antiretroviral therapy (ART), comorbidities, and severe adverse events (SAE) to vaccination was collected. Six hundred and ninety‐seven patients were tested for quantitative anti‐spike antibodies at Time 1, 577 patients had a second detection at Time 2, and 491 patients had the third detection. Baseline characteristics of the study population are reported in Table 1. At the time of vaccine administration, all patients were on ART (except one long‐term nonprogressor); 632 (90.7%) patients had undetectable HIV‐RNA; 12 (1.7%) patients were immunosuppressed due to chemotherapy or other immunosuppressive drugs; 345 (49.5%) patients had at least one COVID‐19 related comorbidity and 155 (22.2%) had two or more comorbidities. No SAEs were reported. Final serological results are available for 694 patients after the first dose, 577 and 491 after the second and third ones, respectively; positive titer (values ≥ 50 AU/ml) was demonstrated in 653 (94.1%), 576 (99.8%), 484 (98.6%) patients, respectively. Only one patient was a nonresponder after completing vaccination, who was a newly diagnosed one for HIV infection. All vaccinations were well tolerated, with no SAEs. BNT162b2 mRNA vaccine was immunogenic and safe in PLWH.

After about 2 years of the severe acute respiratory syndromerelated coronavirus-2 (SARS-CoV-2) pandemic, information about the epidemiology and the outcome of COVID-19 in people living with HIV infection (PLWH) are currently evolving. The last global consensus disclosed by WHO shows HIV infection as an independent risk factor that is associated with a higher risk of death compared to the HIV-negative population. 1 Moreover, as older age represents a determinant for a severe outcome of COVID-19, it must be considered in PLWH getting old as an additional risk factor. Therefore, a world priority is to reduce the susceptible population through immunization, particularly for people with underlying risk factors. In Italy, access to SARS-CoV-2 vaccination has been extended to the population at risk for severe outcomes, including PLWH, starting from March 2021. However, clinical trials before the marketing of these vaccines have not been tested in a large HIV population and therefore, evidence of immunogenicity and safety in PLWH are lacking.

Currently, it has been demonstrated that people with any immune deficiency may have a suboptimal vaccination response and shorter protection compared to the general population. [2] [3] [4] Data on the clinical effectiveness of common vaccines in PLWH are still partial and often difficult to compare as they are based on single experiences, different baseline features, and limited samples. Data appears to confirm a less protective response to common vaccines in HIV-infected patients, compared to the general population. 4 Immunogenicity levels are largely related to CD4+ cell count, viral load (VL), and disease stage. 5 Concerning anti-SARS-CoV-2 vaccination in PLWH, some data have been recently published. Overall, the initial experience appears to be positive in terms of safety and immunogenicity in a limited follow-up. 6, 7 Another critical element is represented by the identification of more accurate timing to proceed with the administration of a vaccine in PLWH, especially for those people who need to start antiretroviral therapy (ART). It is widely accepted by the scientific community that the reconstitution of the immune system induced by ART can increase the immunogenicity of vaccinations in relation to the increase of CD4+ cell count. However, this recommendation is in open conflict with the strategy of early immunization for SARS-CoV-2 of the susceptible population in a pandemic era. 8 Since March 21, 2021, the Italian government issued recommendations on the vaccination of PLWH, using the BNT162b2 vaccine. The Pfizer-BioNTech BNT162b2 mRNA vaccine has been tested for safety and efficacy in a multinational randomized placebocontrolled trial with more than 40 000 participants, 9 of which 196 were PLWH. This study demonstrates the immunogenicity and safety of the vaccine over a median of 2 months.

In our retrospective observational monocentric study, we describe the experience of an Italian reference HIV/AIDS center, with particular insights into immunologic response to BNT162b2 vaccine in a larger cohort of PLWH after 3 months from complete vaccination. Moreover, we collected data about vaccine safety after the first and second administrations. Lastly, we assessed the correlation between clinical data and anti-receptor binding domain (RBD) title at three time points.

Over 1000 outpatients HIV infected are followed in the Clinic of Infectious Diseases, University of Bari. All outpatients aged ≥18 with high sensitivity and specificity, near 100%. 9 HIV VL was determined with RT-PCR, where <20 copies/ml is considered undetectable. CD4+ and CD8+ T-cell counts were determined by flow cytometry analysis in peripheral blood.

Continuous variables were presented as means and standard deviation or as geometric means and 95% CI. Categorical variables (age, sex, hypertension, diabetes, dyslipidaemia, cardiac, and/or vascular disease, chronic obstructive pulmonary disease) were presented as N (%).

The correlation between IgG title and clinical data (CD4+ cell count, CD8 cell count, CD4/CD8 ratio, and VL) were analyzed using multivariate linear regression.

Moreover, occasional viral blips were noticed after the complete vaccination, during planned outpatient control due to HIV infection.

In the study period, a total of 697 participants were enrolled, with an age ranging between 19 and 79 years, 521 were male (74.7%).

The distribution is described in Table 1 Table 4 .

After 3 months, a non-protective title was observed in seven patients, whose clinical features are described in Table 5 This study describes the immunogenicity and safety of the BNT162b2 mRNA vaccine and clinical characteristics of PLWH in follow-up in our Clinic, before and after completing vaccination for SARS-CoV-2. In our setting, the BNT162b2 vaccine was found to be immunogenic and safe for all patients we vaccinated, with an immunogenicity rate even higher than expected if compared to previous studies. 6, 7 There are at least two possible explanations to this finding. The first one is that the enrolled population appears to be apparently younger, compared to the entire population with HIV infection in follow-up in our Center. Indeed, elderly PLWH were previously included in risk categories with priority for vaccination, because of their age, in accordance with the Italian government policy. Therefore, they completed vaccination in the previous months elsewhere, and for that reason they were not included in the study. A secondary aim of the study was to investigate the possible correlation between patient characteristics and response to the BNT162b2 mRNA vaccine. However no statistically significant correlation was observed between antibodies title for anti-RBD IgG and immunological and virologic characteristics measured following the first and second administration, as well as 3 months after the second vaccination. Although in other studies a reduced (IgG positive with neutralizing antibodies title negative 10 ) or delayed (e.g., 2 months 11 ) antibody production was found in PLWH with <200 cell/ µl after SARS-CoV-2 infection, in our study BNT162b2 vaccine was found immunogenic for 98.6% of PLWH enrolled, including patients with CD4+ cell count <200 cell/µl. Moreover, humoral response to SARS-CoV-2 mRNA vaccination in patients with other immunodeficiencies (e.g., cancer, rheumatic disease) has been analyzed in other studies 12,13 and a high rate of anti-RBD antibody production was found, slightly less compared with our entire cohort. The possible explanation is that enrolled people in our study were mainly immunocompetent, only 2.0% had <200 CD+ cell/µl and 1.7% any im- BNT162b2 in a cohort of 88 PLWH patients, who received the prime dose and 52 patients who received the boost. They found that those titers were significantly lower in PLWH having a CD4:CD8 T-cell ratio < 0.5. 15 A similar difference was observed when patients were categorized in groups with CD4 cell counts above and below 25%, suggesting that CD4 T-cell immunity is associated with humoral vaccine-induced immunity in the early phase after priming. Our study did not find any correlation between the CD4:CD8 T-cell ratio or Furthermore, given that the BNT162b2 vaccine induces a lower antibody titer in older individuals, 16 although, the rate of mild/moderate AEs was collected after the end of complete vaccination and data collection was lower than that reported in other clinical trials. 18, 19 This difference was probably due to the different ways in which AE was monitored: simultaneously with administration in other trials and at the end of the study in our setting.

During follow-up and during the period between two doses of vaccine, SARS-CoV-2 infections were not found in the vaccinated population.

The main limitations of this study include lack of a control group, heterogeneity of study population in sex, age, and immunological state and limited follow-up. On the contrary, our study is characterized by a larger cohort study group with a follow-up, that, although limited, reaches a more extended time point, compared with other studies. 6, 7 

Clinical features and prognostic factors of COVID-19 in people living with HIV hospitalized with suspected or confirmed SARS-CoV-2 infection

British HIV Association guidelines on the use of vaccines in HIV-positive adults 2015

The management of geriatric and frail HIV patients. A 2017 update from the Italian guidelines for the use of antiretroviral agents and the diagnostic clinical management of HIV-1 infected persons

Vaccination in the adult patient infected with HIV: a review of vaccine efficacy and immunogenicity

Guidance on vaccination of HIV-infected children in Europe

Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in people living with HIV-1

Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2 A trial

Evaluation of Abbott anti-SARS-CoV-2 CMIA IgG and Euroimmun ELISA IgG/IgA assays in a clinical lab

COVID-19 in people living with HIV: clinical implications of dynamics of the immune response to SARS-CoV-2

High antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with rheumatic and musculoskeletal diseases

Weak immunogenicity after a single dose of SARS-CoV-2 mRNA vaccine in treated cancer patients

Qualitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV

Humoral immune response following prime and boost BNT162b2 vaccination in people living with HIV on antiretroviral therapy

The BNT162b2 mRNA vaccine elicits robust humoral and cellular immune responses in people living with HIV

Effect of influenza vaccination on viral replication and immune response in persons infected with human immunodeficiency virus receiving potent anti-retroviral therapy

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine

How to cite this article: Milano E, Ricciardi A, Casciaro R, et al. Immunogenicity and safety of the BNT162b2 COVID-19 mRNA vaccine in PLWH: A monocentric