Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy

Brumme, Zabrina L.; Mwimanzi, Francis; Lapointe, Hope R.; Cheung, Peter; Sang, Yurou; Duncan, Maggie C.; Yaseen, Fatima; Agafitei, Olga; Ennis, Siobhan; Ng, Kurtis; Basra, Simran; Lim, Li Yi; Kalikawe, Rebecca; Speckmaier, Sarah; Moran-Garcia, Nadia; Young, Landon; Ali, Hesham; Ganase, Bruce; Umviligihozo, Gisele; Omondi, F. Harrison; Atkinson, Kieran; Sudderuddin, Hanwei; Toy, Junine; Sereda, Paul; Burns, Laura; Costiniuk, Cecilia T.; Cooper, Curtis; Anis, Aslam H.; Leung, Victor; Holmes, Daniel; DeMarco, Mari L.; Simons, Janet; Hedgcock, Malcolm; Romney, Marc G.; Barrios, Rolando; Guillemi, Silvia; Brumme, Chanson J.; Pantophlet, Ralph; Montaner, Julio S.G.; Niikura, Masahiro; Harris, Marianne; Hull, Mark; Brockman, Mark A.

Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely understood. We measured circulating antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, ACE2 displacement and live viral neutralization activities one month following the first and second COVID-19 vaccine doses in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525–935) cells/mm(3). Nadir CD4+ T-cell counts ranged as low as <10 (median 280; IQR 120–490) cells/mm(3). After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was significantly associated with 0.2 log(10) lower anti-RBD antibody concentrations (p=0.03) and ~11% lower ACE2 displacement activity (p=0.02), but not lower viral neutralization (p=0.1) after one vaccine dose. Following two doses however, HIV was no longer significantly associated with the magnitude of any response measured. Rather, older age, a higher burden of chronic health conditions, and having received two ChAdOx1 doses (versus a heterologous or dual mRNA vaccine regimen) were independently associated with lower responses. After two vaccine doses, no significant correlation was observed between the most recent or nadir CD4+ T-cell counts and vaccine responses in PLWH. These results suggest that PLWH with well-controlled viral loads on antiretroviral therapy and CD4+ T-cell counts in a healthy range will generally not require a third COVID-19 vaccine dose as part of their initial immunization series, though other factors such as older age, co-morbidities, vaccine regimen type, and durability of vaccine responses will influence when this group may benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment and/or who have low CD4+ T-cell counts are needed.