• 41% concordance was observed across the three approaches for the classification of late HIV diagnosis- CD4 count, ambiguity rate, and phylogenetic reconstruction • The combined approaches identified 114 individuals (3.1%) falsely classified as diagnosed late • These misclassified cases showed lower viral loads, consistent with acute infection • Improving classification can strengthen HIV surveillance accuracy and inform public health policies 41% concordance was observed across the three approaches for the classification of late HIV diagnosis- CD4 count, ambiguity rate, and phylogenetic reconstruction The combined approaches identified 114 individuals (3.1%) falsely classified as diagnosed late These misclassified cases showed lower viral loads, consistent with acute infection Improving classification can strengthen HIV surveillance accuracy and inform public health policies Late HIV diagnosis is associated with a higher impact on treatment outcomes and a potential for prolonged transmissibility of HIV-1 infection. The consensus definition for late HIV diagnosis is problematic. It was updated in 2022, however this definition relies on information that might not be clinically available. The aim of this study was assess of late HIV diagnosis using alternative parameters, in addition to the definition of CD4 cell count, namely sequence ambiguity rate and estimated time of infection inferred through phylogenetic analysis. Clinical, socio-demographic and genotypic information from 3668 ART-naïve individuals living with HIV was retrieved from the REGA database. Individuals were classified according to three approaches: 1) CD4 cell count; 2) Sequence ambiguity rate; 3) Phylogenetic reconstruction using TreeTime to estimated the time of Most Recent Common Ancestor (MRCA) as a proxy for time of infection. Based on CD4 cell count, 53.8% of individuals had a late diagnosis and 46.2% had a non-late diagnosis. Based on sequence ambiguity rate, 57.8% had a chronic and 42.2% had a recent infection, and 86.4% had an estimated time of infection of more than 3 years while 13.6% had less than 3 years. 114 individuals were classified as diagnosed late by CD4 criteria, showed evidence of recent infection based on low ambiguity rates and MRCA estimates under three years. These individuals had significantly lower viral loads compared with true late diagnoses (median 61358 vs 134730 copies/mL; p<0.001). Overall, 41% of individuals were consistently classified across all three methodologies. The definition of late diagnosis remains a major challenge. Alternative and complementary methodologies, such as the use of viral loads, combined with some more clinical information may improve the lack of baseline data.
Miranda et al. (Sun,) studied this question.