Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, 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/mm3, though nadir CD4+ T-cell counts ranged as low as <10 cells/mm3. After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability.

Incident drug resistance rates were low with 'real-world' use of INSTI-based regimens. However, incomplete ART adherence and low CD4 cell count were associated with increased resistance rates regardless of which INSTI was prescribed. Provide adherence support and monitor for drug resistance.

Background Longer-term humoral responses to two-dose COVID-19 vaccines remain incompletely characterized in people living with HIV (PLWH), as do initial responses to a third dose. Methods We measured antibodies against the SARS-CoV-2 spike protein receptor-binding domain, ACE2 displacement and viral neutralization against wild-type and Omicron strains up to six months following two-dose vaccination, and one month following the third dose, in 99 PLWH receiving suppressive antiretroviral therapy, and 152 controls. Results Though humoral responses naturally decline following two-dose vaccination, we found no evidence of lower antibody concentrations nor faster rates of antibody decline in PLWH compared to controls after accounting for sociodemographic, health and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after two doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though Omicron-specific responses were consistently weaker than against wild-type. Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses. Conclusion PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after two- and three-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.

Background. Our understanding of COVID-19 vaccine immune responses in people living with HIV (PLWH) remains incomplete. Methods. We measured circulating antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and ACE2 displacement activities after one and two COVID-19 vaccine doses in 100 adult PLWH and 152 controls. Results. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm3. Median nadir CD4+ T-cell counts were 280 (IQR 120-490) cells/mm3, and ranged as low as 9 cells/mm3. After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with 0.2 log10 lower anti-RBD antibody concentrations (p=0.03) and ~7% lower ACE2 displacement activity (p=0.037) after one vaccine dose. Following two vaccine doses however, the association between HIV and weaker responses no longer remained. Rather, older age, a higher burden of chronic health conditions, and having received two ChAdOx1 doses (as opposed to a heterologous or dual mRNA vaccine regimen) were the most significant correlates of weaker humoral responses. No significant association was observed between the most recent or nadir CD4+ T-cell counts and responses to COVID-19 vaccination in PLWH following two vaccine doses. Conclusions. These results suggest that PLWH whose viral loads are well-controlled on antiretroviral therapy and whose CD4+ T-cell counts are 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, type of initial vaccine regimen 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.

Background: Longer-term humoral responses to two-dose COVID-19 vaccines remain incompletely characterized in people living with HIV (PLWH), as do initial responses to a third dose. Methods: We measured antibodies against the SARS-CoV-2 spike protein receptor-binding domain, ACE2 displacement and viral neutralization against wild-type and Omicron strains up to six months following two-dose vaccination, and one month following the third dose, in 99 PLWH receiving suppressive antiretroviral therapy, and 152 controls. Results: Though humoral responses naturally decline following two-dose vaccination, we found no evidence of lower antibody concentrations nor faster rates of antibody decline in PLWH compared to controls after accounting for sociodemographic, health and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after two doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though anti-Omicron responses were consistently weaker than against wild-type. Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses. Conclusion: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after two- and three-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.