SARS-CoV-2 mRNA Vaccine Response in People Living with HIV According to CD4 Count and CD4/CD8 Ratio

Background: Our aim was to estimate the rates of not achieving a robust/above-averagehumoral response to the COVID-19 mRNA vaccine in people living with HIV (PLWH) who received 2 doses and to investigate the role of the CD4 and CD4/CD8 ratio in predicting the humoralresponse. Methods: We evaluated the humoral anti-SARS-CoV-2 response 1-month after the secondand third doses of COVID-19 mRNA vaccine as a proportion of not achieving a robust/aboveaverageresponse using two criteria: (i) a humoral threshold identified as a correlate of protectionagainst SARS-CoV-2 (<90% vaccine efficacy): anti-RBD < 775 BAU/mL or anti-S < 298 BAU/mL,(ii) threshold of binding antibodies equivalent to average neutralization activity from the levels ofbinding (nAb titer < 1:40): anti-RBD < 870 BAU/mL or anti-S < 1591 BAU/mL. PLWH were stratifiedaccording to the CD4 count and CD4/CD8 ratio at first dose. Logistic regression was used to comparethe probability of not achieving robust/above-average responses. A mixed linear model was usedto estimate the mean anti-RBD titer at various time points across the exposure groups. Results: atotal of 1176 PLWH were included. The proportions of participants failing to achieve a robust/aboveaverageresponse were significantly higher in participants with a lower CD4 and CD4/CD8 ratio,specifically, a clearer gradient was observed for the CD4 count. The CD4 count was a better predictorof the humoral response of the primary cycle than ratio. The third dose was pivotal in achievinga robust/above-average humoral response, at least for PLWH with CD4 > 200 cells/mm3 and aratio > 0.6. Conclusions: A robust humoral response after a booster dose has not been reached by50% of PLWH with CD4 < 200 cells mm3. In the absence of a validated correlate of protections in theOmicron era, the CD4 count remains the most solid marker to guide vaccination campaigns in PLWH.