Causes of death in adults living with HIV in South Africa: A single-centre postmortem study

Background: Mortality among people living with HIV (PLWH) in developing settings remains elevated, despite high coverage with antiretroviral therapy (ART), with 70% - 80% being virally suppressed (VS). Objectives: This study aimed to determine cause-specific mortality in PLWH in South Africa. Method: An autopsy study with detailed medical record review was undertaken in PLWH dying in hospital. Minimally invasive autopsies were performed on 38 VS and 21 unsuppressed PLWH (>= 18 years) dying in hospital between May 2018 and April 2022. We assessed clinical and histological findings to determine underlying, contributing, and immediate causes of death (CODs). Results: Median CD4 counts were 180 and 42 cells/mm3 in patients with and without VS respectively. Leading immediate CODs in both VS and unsuppressed PLWH were respiratory failure, sepsis, and septic shock; leading contributing CODs in decreasing order of frequency in both groups were acute kidney injury (AKI), bacterial pneumonia, immunological failure, gastroenteritis and current tuberculosis. Leading underlying CODs in both groups were hypertension, current tuberculosis, malignancies, and chronic obstructive pulmonary disease. VS was associated with lower risk of septic shock and AKI. Conclusion: VS on ART appeared to reduce risk of death from specific pathologies. However, infections, multi-organ failure, non-AIDS-defining malignancies, and metabolic diseases remain important CODs. Incomplete immune reconstitution appears to be a key contributor to premature death.