Abstract
BACKGROUND: We investigated in-hospital mortality trends across waves of different SARS-CoV-2 variants and assessed the effect of COVID-19 immunization among people with HIV (PWH). METHOD: We analyzed individual-level data from the WHO Global Clinic Platform comprising 823 845 hospitalized children and adults from 61 countries. Survival analyses were used to assess the association of HIV co-infection with in-hospital mortality across SARS-CoV-2 pre-Delta, Delta, and Omicron variant waves. FINDINGS: PWH experienced significantly higher in-hospital mortality compared to HIV-negative individuals across all variant waves. Adjusted hazard ratios (aHRs) for PWH mortality were 1.85 [95% confidence interval (CI) 1.76-1.93] during the pre-Delta wave, 1.58 (95% CI 1.42-1.74) during the Delta wave, and 3.07 (95% CI 2.75-3.42) during the Omicron wave. In-hospital mortality risk was notably higher in PWH with CD4 + cell count 200 cells/μl or less. While mortality declined modestly between pre-Delta and Delta waves in both HIV-negative (10% reduction) and HIV-positive populations (9% reduction), the decline was more substantial for HIV-negative individuals during the Omicron wave (from 18.9 to 8%) than for PWH (from 24.2 to 19.3%) relative to the Delta wave. INTERPRETATION: Although in-hospital mortality among HIV-negative individuals declined markedly during the Omicron wave, reduction in PWH was less pronounced, leading to a relatively higher mortality risk for this group. These findings highlight the need for adherence to WHO recommendations on booster vaccinations and therapeutics for populations at elevated risk of severe COVID-19 outcomes, including PWH.