A cross-sectional study to characterize local HIV-1 dynamics in Washington, DC using next-generation sequencing

Abstract

Washington, DC continues to experience a generalized HIV-1 epidemic. We characterized the local phylodynamics of HIV-1 in DC using next-generation sequencing (NGS) data. Viral samples from 68 participants from 2016 through 2017 were sequenced and paired with epidemiological data. Phylogenetic and network inferences, drug resistant mutations (DRMs), subtypes and HIV-1 diversity estimations were completed. Haplotypes were reconstructed to infer transmission clusters. Phylodynamic inferences based on the HIV-1 polymerase (pol) and envelope genes (env) were compared. Higher HIV-1 diversity (n.s.) was seen in men who have sex with men, heterosexual, and male participants in DC. 54.0% of the participants contained at least one DRM. The 40-49 year-olds showed the highest prevalence of DRMs (22.9%). Phylogenetic analysis of pol and env sequences grouped 31.9-33.8% of the participants into clusters. HIV-TRACE grouped 2.9-12.8% of participants when using consensus sequences and 9.0-64.2% when using haplotypes. NGS allowed us to characterize the local phylodynamics of HIV-1 in DC more broadly and accurately, given a better representation of its diversity and dynamics. Reconstructed haplotypes provided novel and deeper phylodynamic insights, which led to networks linking a higher number of participants. Our understanding of the HIV-1 epidemic was expanded with the powerful coupling of HIV-1 NGS data with epidemiological data.

Figure 1

Cladogram of the pol and env concatenated genes of Washington, DC showing sex, race/ethnicities, and risk factors in rings. All phenotypes present are represented with different colors, see legend. All sequences were subtype B. Well-supported clades are depicted. MSM = men who have sex with men; HRH = heterosexuals; IDU = injection drug users; UNK = unknown; OTH = other. Numbers correspond to the de-identified participant.

Figure 2

Cluster network (HIV-TRACE) of (I) consensus pol and env genes and (II) haplotypes reconstructed with PredictHaplo for PR, RT, int, V1V2 and V3 genes of Washington, DC participants by risk factor and race/ethnicity. Numbers correspond to the de-identified participant. Some participants have multiple HIV-1 haplotypes.