Hidden Burden of Opportunistic Infections among Hospitalised Adults with HIV: Post-mortem Evidence of Diagnostic Gaps in South Africa
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1
Vaccines and Infectious Disease Analytics Research Unit (WITS-VIDA), Soweto, Johannesburg, South Africa
2
Liverpool School of Tropical Medicine (LSTM), Liverpool, United Kingdom
Popul. Med. 2026;8(Supplement Supplement 1):A637
ABSTRACT
INTRODUCTION:
Undiagnosed opportunistic co-infections remain major contributors to mortality among people living with HIV (PLWH). Using post-mortem minimal invasive tissue sampling (MITS), we investigated pathogen-specific causes of death in hospitalised adults with HIV in South Africa.
METHODS:
This mortality surveillance study enrolled adults aged 18–64 years (HIV positive and unknown HIV status) who died of non-traumatic causes in medical wards at two Johannesburg hospitals. Within 72 hours post-mortem, MITS collected blood, cerebrospinal fluid, and liver, lung, and brain tissue. Samples underwent microbiological, molecular, and histopathological testing, and findings were integrated with clinical and verbal autopsy data by a multidisciplinary panel to assign causes of death according to World Health Organization (WHO) standards.
RESULTS:
Among 813 decedents, consent was obtained from next-of-kin for MITS in 286 cases. Of the 212 deaths analysed, 197 (93%) were confirmed to have been living with HIV. Opportunistic infections were identified in the causal pathway to death in 49% (96/197) of PLWH, yielding 107 pathogens. Tuberculosis (TB) predominated (69% 74/107), followed by Cryptococcosis (20%; 21/107) and Pneumocystis jirovecii pneumonia (11%, 12/107). Notably, 24% (26/107) of opportunistic pathogens in the causal pathway to death were missed antemortem. Among Tuberculosis cases, 65% (48/74) were new presentations, and 42% (20/48) were confirmed by post-mortem testing, despite antemortem work-up in 65% (13/20). Advanced HIV disease (AHD) was present in 83% (80/96) with opportunistic infections, including in 19% (18/96) newly diagnosed with HIV. Among known PLWH (81%; 78/96), 56% (44/78) were receiving antiretroviral therapy (ART) and 41% (18/96) were virally suppressed. Among decedents with an opportunistic infection, these infections were the immediate cause of death in 33% (32/96).
CONCLUSIONS:
Post-mortem MITS revealed a high burden of previously undiagnosed opportunistic infections, underscoring persistent diagnostic gaps and public health inequalities affecting hospitalised PLWH. Analysis of sampled cases is ongoing.