People living with HIV who are receiving suppressive antiretroviral therapy mount strong humoral responses to two and three doses of COVID-19 vaccine


BACKGROUND: Immune responses to COVID-19 vaccines, particularly to third doses, remain incompletely characterized in people living with HIV (PLWH).
METHODS: We are monitoring immune responses to COVID-19 vaccination in a cohort of 99 adult PLWH and 152 controls, aged 22-88 years, in British Columbia, Canada. All PLWH were receiving suppressive ART, with median CD4+ T-cell counts of 715 (Q1-Q3 545-943) cells/mm3at cohort entry. In samples collected one month after the second and third COVID-19 vaccine doses, we quantified serum antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD) using the Roche Elecsys anti-SARS-CoV-2 assay, and measured viral neutralization activity in plasma against the original (USA-WA1/2020) and Omicron (BA.1) SARS-CoV-2 strains.
RESULTS: We previously reported that, at one month following the second COVID-19 vaccine dose, and after adjustment for sociodemographic, health, and vaccine-related variables, HIV infection was not associated with a difference in either anti-RBD antibody concentration nor live virus neutralization activity compared to responses observed in controls. In PLWH, there was no significant correlation between the most recent (or nadir) CD4+ T-cell count and vaccine responses after two doses. Rather, at this timepoint, older age, a higher burden of chronic health conditions, and having received two ChAdOx1 doses (as opposed to mRNA or heterologous regimens) were associated with lower responses. One month following the third dose, anti-RBD serum antibodies increased by 0.4 log10higher on average, and viral neutralization by four-fold higher on average, than values observed one month after the second dose, in both PLWH and controls (Wilcoxon paired test p<0.0001 for all within-group comparisons between time-points). Importantly, there was no significant difference between PLWH and controls in terms of the magnitudes of post-3rd-dose responses. In a subset of 24 participants assessed to date, the ability to neutralize Omicron after three doses was on average 8-fold lower than the pandemic founder strain (p<0.0001).
CONCLUSIONS: In PLWH with well-controlled viral loads on therapy and CD4+ T-cell counts in a healthy range, humoral responses to two and three COVID-19 vaccine doses are comparable to individuals without HIV. Third COVID-19 vaccine doses induce responses capable of neutralizing Omicron to some extent.

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