Beyond CD4 counts: Multi‐biomarker assessment of estimated time since HIV ‐1 infection and risk factors for late diagnosis

Abstract Background Late diagnosis (LD) of HIV, defined as CD4 count Methods We conducted a prospective cohort study of newly diagnosed people with HIV in Sweden between November 2017 and December 2022. Individuals were classified as LD or non‐LD according to an updated consensus definition. We applied an MBM combining CD4 count, pol polymorphism counts, pol next‐generation sequencing diversity, HIV‐1 limiting‐antigen avidity assay and last negative HIV test to probabilistically derive ETI distributions. Results More than half (52.4%) were classified as LD. Risk factors for LD included age >50 years (adjusted odds ratio (aOR) 2.94, 95% CI 1.42–6.09), origin in Asia and Pacific (aOR 4.53, 95% CI 1.81–11.32) and HIV acquisition in Asia and Pacific (aOR 2.28, 95% CI 1.08–4.83). Men who have sex with men had reduced risk of LD versus persons with heterosexual acquisition (aOR 0.38, 95% CI 0.22–0.64). ETI in 344 individuals revealed diagnostic delays; 41% (95% CrI 36.7–46.0) were diagnosed within 1 year: 71% of non‐LDs (CrI 95% 65.0–77.7) versus 12% of LDs (95% CrI 8.4–16.2). Among LDs, over 60% remained undiagnosed beyond 3 years. Conclusions Multi‐biomarker ETI reveals that most HIV‐1 infections remain undiagnosed for over 1 year. The updated LD definition correlates better with time since infection and ETI distributions show substantial diagnostic delays. Expanded testing strategies targeting heterosexual and older populations are urgently needed.