SARS-CoV-2 VACCINE IMMUNOGENICITY in PLWH in the NETHERLANDS

ABSTRACT

Background: Vaccines can be less immunogenic in people living with HIV (PLWH). So far, the immune response after SARS-CoV-2 vaccination of PLWH is not well-established. Methods: A prospective cohort study in 22 HIV treatment centres in the Netherlands examined the immunogenicity of SARS-CoV-2 vaccines in PLWH. Included were adult PLWH without prior COVID-19 infection, invited by the national vaccination programme to receive the BNT162b2, mRNA-1273, ChAdOx1-S or Ad26.COV2.S vaccine. Data from HIV-negative healthy controls were acquired from 2 concurrent prospective vaccination trials. The primary endpoint was the anti-SARS-CoV-2 IgG response (Liaison Trimeric Spike IgG in BAU/ml) measured 4-6 weeks after vaccination with one of the 2 mRNA vaccines in PLWH versus controls. Secondary endpoints included antibody response according to sex, CD4+ T-cell count, and vaccine reactogenicity. Results: Between February 14th and September 7th 2021, 1269 PLWH were enrolled and complete results were available for 1148 PLWH as well as for 440 healthy controls. 879 of the PLWH were vaccinated with BNT162b2 while 100, 150 and 19 had received mRNA-1273, ChAdOx1-S and 19 Ad26.COV2.S respectively. Their median age was 53 years [IQR 44-60], 85.5% was male, the median CD4+ T-cell count was 710/μ L [IQR 520-913]. 99% was on cART with HIV-RNA <50 copies/ml in 97.7%. The control group consisted of 440 healthy people;247 vaccinated with mRNA-1273, 94 with BNT162b2, 26 with ChAdOx1-S and 73 with Ad26.COV2.S. Their median age was 43 [IQR 33-53] and 28.6% was male. PLWH had a significantly lower anti-SARS-CoV-2 RBD IgG response compared to controls (mean value of 2171 BAU/mL (95% CI 1888-2453) versus 3586 BAU/ml (95% CI 3250-3922, p<0.001)). In the multivariable analysis, being HIV positive, age >65 years, being male and having received a non-mRNA vaccination were all independently associated with a lower antibody concentration (p<0.01 for all). In the PLWH vaccinated with BNT162b2 or mRNA-1273, mean antibody levels were significantly lower in those with a CD4+ T-cell counts <250/μ L (1617 BAU/mL, 95% CI 828-2407) compared to CD4 ≥250/μ L (2486 BAU/ml 95% CI 2149-2824, p=0.002). Reactogenicity occurred in 55 and 50% after the first and second vaccination respectively and were generally mild without vaccine-related SAE. Conclusion: After vaccination with BNT162b2 or mRNA-1273, Anti-Spike IgG levels were lower in PLWH compared to healthy controls. In PLWH, a CD4+ T cell count <250/μ L was associated with lower antibody concentration.