ABSTRACT
Background: Transient viremia has been reported after COVID-19 mRNA vaccination in ART-suppressed PWH, suggesting a stimulatory effect on the HIV reservoir. A recent study also reported that Nef-specific CD8+ T cells increased and acquired granzyme-B effector function following COVID-19 mRNA vaccination, and that this correlated with markers of immune-mediated suppression of HIV-transcribing cells. That study however did not investigate HIV viremia, nor did it detect significant reservoir size changes in the 13 participants assessed. We investigated changes in HIV viremia and reservoir size following COVID-19 mRNA vaccination in 62 ART-treated PWH. Method(s): Participants (55 male;7 female) were sampled pre-vaccination, and one month after the first and second doses. Plasma HIV loads (pVL) were measured using the Cobas 6800 (LLOQ 20 copies/mL). Intact and total HIV copies/million CD4+ T cells were measured using the Intact Proviral DNA Assay. Anti-SARS-CoV-2 S serum antibody concentrations were measured using the Roche Elecsys Anti-S assay. Result(s): Pre-vaccination, 82% of participants had pVL < 20 copies/mL (max 110 copies/mL). No significant changes in pVL were observed post-vaccination (all p >0.4): one month post-first and second doses, 79% and 85% of participants had pVL < 20 copies/mL (max 183 and 79 copies/mL), respectively. Pre-vaccination, the median intact reservoir size was 80 (IQR:28-197;n=46) HIV copies/million CD4+ T cells. Intact reservoir size did not change significantly post-vaccination (all p >0.2): one month post-first and second doses, medians were 85 (IQR: 29-184;n=46) and 65 (IQR:22-168;n=29) copies/million CD4+ T cells, respectively. No significant changes in total, nor 5' and 3' defective proviral burdens were observed post-vaccination (all p >0.1), nor were any significant changes observed in any outcome upon stratification by sex, COVID-19 vaccine regimen, or ART regimen (here, multiple tests were addressed using q-values). Finally, no correlations were observed between the SARS-CoV-2 anti-S antibody response magnitude, and either the magnitude of change in reservoir size, nor the observation of detectable viremia, following the first and second vaccine doses (all p >0.2). Conclusion(s): Despite evidence that COVID-19 mRNA vaccination may induce HIV-specific immune responses, we observed no measurable changes in reservoir size nor lasting plasma viremia following COVID-19 mRNA immunization, regardless of anti-SARS-CoV-2 antibody response magnitude. (Figure Presented).
ABSTRACT
Background: Limited data exist regarding the immune benefits of fourth COVID-19 vaccine doses in people with HIV (PWH) receiving antiretroviral therapy (ART), particularly given that most have now experienced SARS-CoV-2 infection. We measured the effect of fourth doses on SARS-CoV-2 neutralization in 63 PWH, including 19 SARS-CoV-2-naive and 44 SARS-CoV-2-experienced participants. Method(s): Wild-type (WT)-, Omicron-BA.5 and Omicron-BQ.1-specific neutralization activities were longitudinally quantified using live virus assays up to one month post-fourth vaccine dose. Multiple linear regression was used to investigate the relationship between sociodemographic, health and vaccinerelated variables and SARS-CoV-2 neutralization. Result(s): Participants (54 male;9 female) received monovalent (44%) or bivalent (56%) mRNA fourth doses. In COVID-19-naive PWH, a fourth dose enhanced WT- and BA.5-specific neutralization modestly above three-dose levels (p=0.1). In COVID-19-experienced PWH, a fourth dose enhanced WT neutralization modestly (p=0.1) and BA.5 neutralization significantly (p=0.002). Consistent with the humoral benefits of 'hybrid' immunity, the highest neutralization was observed in COVID-19-experienced PWH after a fourth dose. Of note, PWH with Omicron-era infections exhibited higher WT-specific (p=0.04), but comparable BA.5- or BQ.1-specific neutralization, compared to PWH with pre-Omicron-era infections. Overall, BA.5 neutralization was significantly lower than WT in all participants regardless of COVID-19 experience, and BQ.1 neutralization was significantly lower than BA.5 (all p< 0.0001). In multivariable analyses, fourth dose valency did not significantly affect neutralization magnitude, nor did sex, age nor CD4+ T-cell count (neither recent nor nadir). Rather, an mRNA-1273 fourth dose (versus a BNT162b2 one) was the strongest correlate of WT-specific neutralization, while prior COVID-19, regardless of infection era, was the strongest correlate of BA.5 and BQ.1-specific neutralization post-fourth dose. Conclusion(s): Fourth COVID-19 vaccine doses, irrespective of valency, benefit PWH regardless of prior SARS-CoV-2 infection, but the highest neutralization of Omicron-BA.5 and BQ.1 variants post-fourth dose occurred in PWH with hybrid immunity. These results support existing recommendations that all adults receive a fourth immunization within 6 months of their third vaccine dose (or their most recent SARS-CoV-2 infection). (Figure Presented).