Phylogenetics of the Danish HIV Epidemic: The Role of Very Late Presenters in Sustaining the Epidemic

Background: In Denmark, 300 new individuals are diagnosed with HIV every year, despite decades of public health campaigns aimed to raise awareness of potential risk behavior for HIV transmission. It is important to identify the driving forces of the epidemic, to enable more targeted campaigns. The role of very late presenters (VLPs, defined by a CD4 T-cell count of,200 cells/mL at the time of diagnosis) in driving the epidemic is currently not known and was investigated in this study. Methods: We performed phylogenetic analysis to identify potential transmission clusters. One thousand five hundred fifteen partial polymerase sequences from 1515 newly diagnosed individuals in Denmark for whom clinical and epidemiological data existed were included in the study. Results: We identified 46 epidemic clusters, including a total of 502 patients. Median cluster size was 7 patients (range, 4-82). Of the 460 VLPs, 20% were included in a cluster. Through multivariate analysis, it was found that the clusters mainly consisted of Danish individuals with homosexual and intravenous drug use risk behavior, infected in Denmark with subtype B. Large clusters contained significantly more homosexual transmission events, characterized by primary infections, younger age, higher CD4 cell count, and lower viral load compared with the small clusters that contained mostly heterosexual transmission events and VLP. Conclusion: Danish HIV epidemic is driven mainly by younger homosexual men diagnosed during primary HIV infection. VLPs appear more frequently in smaller clusters or as single branches in the phylogeny. The VLP contribution is not of significant importance from a transmission standpoint.