HOW HIV MODULATES the SAFETY and IMMUNOGENICITY of the BNT162b2 COVID-19 VACCINE

ABSTRACT

Background: The pivotal BNT162b2 trials included only ∼60 vaccine recipients, all with well controlled HIV, and there is a need to gather more information on vaccine safety and immunogenicity in diverse populations. This prospective study evaluated solicited and unsolicited adverse events (AEs) and anti-S and anti-NC serological profiles in a diverse cohort of people with HIV undergoing BNT162b2 vaccination (2 doses 3 weeks apart). Methods: Participants completed structured questionnaires modelled on the BNT162b2 trials (FDA submission, Nov 2020) to report solicited and unsolicited AEs in the 7 days after each vaccine dose, indicating severity and duration. Serum samples collected prior to dose-1 (T0) and 3-6 weeks after dose-2 (T1) underwent qualitative anti-NC and quantitative anti-S testing by Elecsys®. Factors associated with T1 anti-S titres were explored in linear regression models including all available parameters. Results: Overall, 259 adults received dose-1 (26% female, 77% white, 44% MSM, 44% history of advanced disease, 31% ≥1 comorbidity, 10% HIV RNA >50 cps/ml [median 122 cps], 7% prior COVID-19 diagnosis, 15% anti-NC positive;median age 48 years, ART duration 7 years, nadir/current CD4 count 225/708 cells/mm3, CD4CD8 ratio 0.8);257 received dose-2. Local AEs were more common after dose-1 than dose-2 (70% vs. 62%, p=0.015), whereas systemic AEs increased with dose-2 (50% vs 60%;p=0.006) (Fig 1a-c);22% experienced moderate-severe systemic AEs after dose-2. Unsolicited AEs (mainly nausea and light-headedness) were reported by 7% after dose-1 and 9% after dose-2. Among 206 participants with T1 samples, 205 (99%) had measurable anti-S (>0.8 U/ml). Anti-S levels were significantly lower at CD4 counts <200 cells/mm3 (Fig 1d). In adjusted regression analyses, factors associated with anti-S titres comprised anti-NC positivity (fold-change 7.39;95% CI 3.92-13.91;p<0.01), HIV viraemia (FC 0.24;0.11-0.50;p<0.01), reporting moderate-severe systemic AEs after dose-2 (FC 1.77;1.03-3.04;p=0.04) and either the CD4 count (FC 1.01;1.00-1.01;p=0.04) or CD4CD8 ratio (FC 1.05;1.00-1.10;p=0.05). Conclusion: In this cohort with HIV, AE patterns after vaccination were similar to those seen in the pivotal BNT162b2 trials and most AEs were mild and short-lived. Whilst prior exposure to SARS-CoV-2 predicted higher anti-S responses, CD4 counts <200 cells/mm3 and low-level viraemia predicted reduced anti-S responses, thus identifying a subset potentially vulnerable to reduced vaccine efficacy.