SARS-CoV-2 mRNA Vaccine Response in People Living with HIV According to CD4 Count and CD4/CD8 Ratio
Vergori A, Tavelli A, Matusali G, Azzini AM, Augello M, Mazzotta V, Pellicanò GF, Costantini A, Cascio A, De Vito A, Marconi L, Righi E, Sartor A, Pinnetti C, Maggi F, Bai F, Lanini S, Piconi S, Levy Hara G, Marchetti G, Giannella M, Tacconelli E, d'Arminio Monforte A, Antinori A, Cozzi-Lepri A, On Behalf Of The Vax-Icona-Orchestra Study.
Background: Our aim was to estimate the rates of not achieving a robust/above-average humoral 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 humoral response.
Methods: We evaluated the humoral anti-SARS-CoV-2 response 1-month after the second and third doses of COVID-19 mRNA vaccine as a proportion of not achieving a robust/above-average response using two criteria: (i) a humoral threshold identified as a correlate of protection against 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 of binding (nAb titer < 1:40): anti-RBD < 870 BAU/mL or anti-S < 1591 BAU/mL. PLWH were stratified according to the CD4 count and CD4/CD8 ratio at first dose. Logistic regression was used to compare the probability of not achieving robust/above-average responses. A mixed linear model was used to estimate the mean anti-RBD titer at various time points across the exposure groups.
Results: a total of 1176 PLWH were included. The proportions of participants failing to achieve a robust/above-average response 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 predictor of the humoral response of the primary cycle than ratio. The third dose was pivotal in achieving a robust/above-average humoral response, at least for PLWH with CD4 > 200 cells/mm3 and a ratio > 0.6.
Conclusions: A robust humoral response after a booster dose has not been reached by 50% of PLWH with CD4 < 200 cells mm3. In the absence of a validated correlate of protections in the Omicron era, the CD4 count remains the most solid marker to guide vaccination campaigns in PLWH.
Keywords: CD4 count; CD4/CD8 ratio; HIV; PLWH; SARS-CoV-2 mRNA vaccine; humoral response.