The role of Late Presenters on HIV-1 transmission clusters in Europe

Abstract

Background: Investigating the role of late presenters (LP) on HIV-1 transmission is important, as they can contribute to the onward spread of HIV-1 virus in the long period before diagnosis, when they are not aware of their HIV status Objective: To describe the clinical and socio-demographic characteristics of HIV-1 infected individuals followed in Europe, to characterize patients in clusters and to compare transmission clusters (TC) in LP vs non-late presenters (NLP) populations. Methods: Clinical, socio-demographic and genotypic information from 38531 HIV-1 infected patients was collected from the EuResist Integrated Database (EIDB) between 1981 and 2019. Sequences were aligned using VIRULIGN. Maximum likelihood (ML) phylogenies were constructed using FastTree. Putative transmission clusters were identified using ClusterPicker v1.332. Statistical analyses were performed using R. Results: 32652 (84.7%) sequences were from subtype B, 3603 (9.4%) were from subtype G, and 2276 (5.9%) were from subtype A. The median age was 33 (IQR: 26.0-41.0) years old and 75.5% of patients were males. The main transmission route was through homosexual (MSM) contact (36.9%) and 86.4% were originated from Western Europe. Most patients were native (84.2%), 59.6% had a chronic infection, and 73.4% had acquired drug resistance (ADR). CD4 count and viral load at diagnosis (log10) presented a median of 341 cells/mm3, and of log10 4.3 copies/mL, respectively. 51.4% of patients were classified as LP and 21.6% patients were inside TCs. Most patients from subtype B (85.6%) were in clusters, compared to subtypes A (5.2%) and G (9.2%). Phylogenetic analyses showed consistent clustering of MSM individuals. In subtype A, patients in TCs were more frequently MSM patients and with a recent infection. For subtype B, patients in TCs were more frequently those with older age (≥ 56), MSM transmission route, originating from Western Europe, migrants, and with a recent infection. For subtype G, patients in TC were more frequently patients with recent infection and migrants. When analysing cluster size, we found that NLP more frequently belonged to large clusters (>8 patients) when compared to LP. Conclusion: While late presentation is still a threat to HIV-1 transmission, LP individuals are more present either outside or in small clusters, indicating a limited role of late presentation to HIV-1 transmission.