Vaccine effectiveness against COVID-19 in-hospital mortality in people living with HIV across SARS-CoV-2 variant waves: Analyses of data from the WHO Global Clinical Platform

There are limited data on the impact of coronavirus disease 2019 (COVID-19) vaccines on mortality among people living with human immunodeficiency virus (HIV) (PLHIV) across different severe acute respiratory syndrome coronavirus 2 variants. We assessed the impact of the COVID-19 vaccine in reducing in-hospital mortality among PLHIV across various severe acute respiratory syndrome coronavirus 2 variant waves. We analyzed individual-level data from 159,150 patients hospitalized with COVID-19 across 43 countries. Flexible parametric survival models were used to estimate the association between COVID-19 vaccination and in-hospital mortality, accounting for HIV status. Among HIV-negative individuals, COVID-19 vaccination reduced the risk of in-hospital mortality by 38 to 42% across all variant waves compared to their unvaccinated counterparts. In PLHIV, the protective effect of vaccination was less pronounced. Vaccinated PLHIV exhibited higher mortality risks compared to unvaccinated HIV-negative individuals: 41% higher during the Omicron wave (adjusted hazard ratio [aHR] 1.41, 95% confidence interval [CI] 1.05–1.89) and no significant difference during the pre-Delta and Delta waves. However, vaccinated PLHIV consistently showed lower mortality risks than unvaccinated PLHIV, with mortality reductions of 60% (aHR 0.40, 95% CI 0.31–0.51) during the pre-Delta period, 50% during Delta (aHR 0.50, 95% CI 0.33–0.75), and 54% during Omicron (aHR 0.46, 95% CI 0.36–0.59). While COVID-19 vaccination significantly reduced inpatient mortality among PLHIV, mortality risks remained elevated compared to HIV-negative individuals, particularly during the Omicron variant wave. Overall, vaccination still offered substantial protection against death for PLHIV compared to unvaccinated PLHIV. These findings underscore the need for targeted vaccination strategies, including booster doses, to protect high-risk populations such as PLHIV, in alignment with World Health Organization recommendations.