Alistair D. Calver

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.

Background: Liver disease is the leading cause of non-AIDS-related mortality in people living with HIV (PLWH). Steatotic liver disease (SLD) is increasingly recognised as an important aetiological factor in liver dysfunction in PLWH. Objectives: This study aimed to determine the post-mortem prevalence and severity of SLD and determine HIV- and non-HIV-related risk factors associated with it. Method: We conducted a retrospective cross-sectional study in which liver histology from 59 deceased people who were infected with HIV was assessed for steatosis, and findings correlated with clinical, epidemiological, and biochemical data. Results: Decedents were predominantly men (33/59); 63% (37/59) were virologically supressed. Median CD4+ T-cell count was 139 cells/µL (interquartile range [IQR]: 47–344). Steatosis was present in 39% (23/59) of decedents: 74% mild, 9% moderate, and 17% severe steatosis. There were no cases of steatohepatitis, and one case with mild fibrosis. Factors associated with SLD were: CD4 T-lymphocyte count > 200 cells/µL (odds ratio [OR]: 3.69; 95% confidence interval [CI]: 1.19–11.44), female sex (OR: 8.5; 95% CI: 2.57–28.17), hypertension (OR: 6.5; 95% CI: 2.05–21.00), and being normal or overweight (OR: 6.75; 95% CI: 1.12–40.56). Virological suppression and duration of antiretroviral drug use were not associated with steatosis. Conclusion: We found a high proportion of SLD with heterogeneous causes in deceased people who were infected with HIV, exceeding previously reported prevalences from elsewhere in Africa. A preserved CD4 count and being female conferred the highest risk for steatosis, underscoring the need for screening in this subgroup and further research to delineate risks in a Southern African population.