Characterizing HIV Transmission Networks Across the United States

Abstract

Background. Clinically, human immunodeficiency virus type 1 (HIV-1) pol sequences are used to evaluate for drug resistance. These data can also be used to evaluate transmission networks and help describe factors associated with transmission risk.Methods. HIV-1 pol sequences from participants at 5 sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort from 2000-2009 were analyzed for genetic relatedness. Only the first available sequence per participant was included. Inferred transmission networks ("clusters") were defined as ≥2 sequences with ≤1.5% genetic distance. Clusters including ≥3 patients ("networks") were evaluated for clinical and demographic associations.Results. Of 3697 sequences, 24% fell into inferred clusters: 155 clusters of 2 individuals ("dyads"), 54 clusters that included 3-14 individuals ("networks"), and 1 large cluster that included 336 individuals across all study sites. In multivariable analyses, factors associated with being in a cluster included not using antiretroviral (ARV) drugs at time of sampling (P < .001), sequence collected after 2004 (P < .001), CD4 cell count >350 cells/mL (P < .01), and viral load 10 000-100 000 copies/mL (P < .001) or >100 000 copies/mL (P < .001). In networks, women were more likely to cluster with other women (P < .001), and African Americans with other African Americans (P < .001).Conclusions. Molecular epidemiology can be applied to study HIV transmission networks in geographically and demographically diverse cohorts. Clustering was associated with lack of ARV use and higher viral load, implying transmission may be interrupted by earlier diagnosis and treatment. Observed female and African American networks reinforce the importance of diagnosis and prevention efforts targeted by sex and race.

Identifying Transmission Clusters with Cluster Picker and HIV-TRACE

“…[1][2][3][4][5][6] The identification of transmission clusters can support epidemiologically linked transmission events, 7 identify putative transmission chains, 8 and reveal mixing between key risk groups and geographic subpopulations. 9 Transmission clusters of HIV infections are typically defined using either genetic distances among sequences 4 or genetic distances in addition to branch support values (e.g., bootstrap values). 3 However, genetic distance and branch support cutoffs markedly vary between studies and the rationale for a given cluster definition is rarely specified.…”

Molecular epidemiology of HIV-1 in Iceland: Early introductions, transmission dynamics and recent outbreaks among injection drug users

“…The molecular epidemiology of HIV-1 has been studied extensively both globally, (Faria et al, 2014;Wertheim et al, 2014) and in limited geographic settings, (Aldous et al, 2012;Bruhn et al, 2014;Ciccozzi et al, 2013;Esbjornsson et al, 2016;Kouyos et al, 2010;Mendoza et al, 2014;Paraskevis et al, 2015) to increase the understanding of the drivers of HIV-1 transmission and to increase the focus of preventive strategies (Brenner et al, 2013).…”

The International Dimension of the U.S. HIV Transmission Network and Onward Transmission of HIV Recently Imported into the United States

“…Transmission networks inferred from genetic sequences allow the study of viral dynamics on a local or national level. [14][15][16][17][18][19] Moreover, these networks provide the means to improve the effect of targeted treatment intervention. 20 Recent work by Wertheim et al 2 has demonstrated how the global diversity of HIV can be efficiently queried for transmission links by comparing genetic distances between isolates.…”