ABSTRACT
Background: We compared the 12-month post primary vaccination humoral immune response to mRNA COVID-19 vaccines in PLHIV and controls. Method(s): PLHIV and HIV-negative healthy controls included in the French national multi-center prospective COVID 19 vaccine cohort study ANRS0001S COV-POPART were analyzed. Percentage (95% CI) of responders (positive anti- Spike SARS-CoV-2 IgG antibodies) and geometric means titers (95% CI) of anti-Spike SARS-CoV-2 IgG antibodies (BAU/mL) were assessed at 1 month and 6 months (M) after the 2nd dose of the primary vaccination and at 12 months in those who received a booster dose. Specific neutralizing antibodies (nAbs) (in vitro neutralization assay against original, Delta and Omicron BA.1 strains) were estimated in a subset of participants. Serological tests (ELISA Euroimmun) and seroneutralization were performed centrally. Result(s): Overall, 858 PLHIV and 1156 controls were included. PLHIV were older than controls: 55.2 years, (49.6-60.6) vs 46.6 years (36.3-56.6) and more frequently male (75.1% vs 48.9%). Among PLHIV at inclusion, 97.3% were under antiretroviral therapy, 95.6% had an undetectable viral load and 71.8% had CD4 counts above 500 cells/mm3. Participants had namely received BNT162b2 as the primary vaccination (93% in PLWHIV vs 84% in controls) and 53.1% had received a booster dose (57.2% in PLHIV (median time after the 2nd dose: 6.1 M [5.9-6.7]) and 50.1% in controls (median time 6.0 M [5.5-6.2])). Percentage of responders after the 2nd dose was lower in PLHIV than controls ((98.7% [97.7;99.3] vs 99.9% [99.5;99.9], p=0.0001)). PLHIV had significantly lower levels of anti-Spike antibodies at 1 M ((1188 [650;2067] vs 1506 [950;2507] BAU/mL, p< 0.0001)) and 6 M (149 [95;235] vs 194 [124;314] BAU/mL, p=< 0.0001) but similar levels at 12 M (520 [269;1198] vs 427 [259;1087] BAU/mL, p=0.3387) (Figure A). PLHIV had significantly lower nAbs against original, Delta and Omicron BA.1 strains at 1, 6 and 12 M after primary vaccination compared to controls. The booster dose significantly increased the titers of nAbs against original and Delta strains and, to a lower extent, against Omicron (Figure B). Conclusion(s): PLHIV had high response rates to mRNA COVID-19 vaccines but lower titers of antibodies and nAbs at 1 and 6 M after primary vaccination than controls. One mRNA booster dose increased SARS-CoV-2 IgG antibodies titers to similar levels to controls but neutralizing activity especially against Omicron remained lower. (Figure Presented).
ABSTRACT
Background: High effectiveness of COVID-19 vaccines was demonstrated. In people living with HIV (PLWHIV), immunogenicity and efficacy of COVID-19 vaccines might be lower. We evaluated the humoral immune response to COVID-19 vaccines in PLWHIV compared to controls without specific comorbidities. Methods: PLWHIV and controls from the French national multi-center prospective COVID 19 vaccine cohort study ANRS0001S COV-PopART were included. Participants with pre-vaccination positive SARS CoV-2 antibodies, history of SARS CoV-2 infection, or positive SARS CoV-2 anti-nucleocapsid (NCP) antibodies were excluded. Percentage (95% confidence interval (CI)) of responders, geometric means (95% CI) of anti-Spike SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies (in vitro neutralization assay) were estimated one month after the second vaccine dose. Serological tests (ELISA Euroimmun) with tests limits and seroneutralization for the original SARS-CoV-2 strain were performed centrally. Results: Among the 6089 participants included, 2625 were PLWHIV or controls;1212 had serological measures available one month after their second dose and 1133 had negative anti-NCP antibodies: 591 PLWHIV and 542 controls. PLWHIV were older than controls: 56.5 years, (51.2-62.2) vs 52.1 years (42.1-62.6) and more frequently male (78.7% vs 52.1%). All PLWHIV were under antiretroviral therapy, 76% had an undetectable viral load and 70.6% had CD4 counts above 500 cells/mm3. Participants had primarily received BNT162b2 (92.4% in PLWHIV vs 88.2% in controls). Proportions of participants who developed anti-Spike IgG (98.5% [97.1;99.3] vs 100.0% [99.3;100.0], p<0.01) and neutralizing antibodies (96.8% [95.0;98.1] vs 99.8 [99.0;100.0], p<0.01) were significantly lower in PLWHIV compared to controls. Of the nine non-responding PLWHIV, all were in CDC stage C, two had detectable HIV viral load and seven had CD4 cell counts below 200/mm3. PLWHIV had similar levels of anti-Spike antibodies (1149.0 [1066.6;1237.8] vs 1299.3 [1208.7;1396.6] BAU/mL, p=0.27) but lower seroneutralization titers (156.8 [141.9;173.2] vs 279.8 [256.1;305.6] IU/mL, p<0.01) than controls (figure). Conclusion: PLWHIV under ARV treatment had high response rates one month after two doses of COVID-19 vaccination. Nonetheless, seroneutralization titers were lower, and non-responders in PLWHIV had a more advanced disease stage. Longer follow-up is needed to gain a better insight into the humoral response after COVID-19 vaccination in PLWHIV.