Phylogenetic analyses of HIV sequences can be used to monitor epidemic trends and help target prevention through the identification of transmission clusters. Characterizing such clusters in NC, where >1,500 new HIV diagnoses are reported annually despite widespread prevention, is needed. We evaluated temporal cluster expansion and epidemic growth to detect “active” clusters as potential intervention targets.
We analyzed 15,247 HIV-1 pol sequences (each from an individual patient) derived from genotypes sampled in NC from 1997-2014 by the largest commercial laboratory. Putative transmission clusters were clades with high branch support (≥0.90) and maximum pairwise genetic distance <3.5% on a maximum-likelihood (ML) tree with the GTR model. Clusters were confirmed and transmission dynamics evaluated using BEAST with Bayesian skyline and relaxed molecular clock priors, inferring internal node ages (for each cluster ≥10 members). Reproductive numbers (R0) for individual large clusters were estimated using birth-death models.
Most samples were from men (71%) with median age 40 years (IQR 32-48), and HIV-1B (98%). 7,647 (50%) sequences were identified in 2,318 clusters (median size 3 members). 74 large clusters (≥10) involved 1,062 patients and were highly supported in BEAST. Compared to non-clustered patients, large clusters were associated with sex (81% vs. 70% men), more recent sampling year (65% vs. 46% ≥2009), younger age (49% vs. 15% ≤30 years), and sampling from Raleigh metropolitan area (54% vs. 42%) [all P<0.001]. However, 16 (22%) large clusters were ≥50% women and had earlier origin dates (1996 vs. 1999) and longer time spans (18 vs. 15 years) than male dominated clusters. The 8 largest clusters (n=22-36 members) originated between 1997 and 2004 and spanned a mean 12.5 years with 2.2 transmissions/year. The median estimates of R0 ranged 1.2-4.1. Most (75%) had highly supported internal nodes 2010-2014, indicating cluster expansion. Most of these clusters were homogenous by sampling region, and all but one were >90% men.
Phylodynamics revealed transmission cluster expansion in this densely sampled region and allowed estimates of R0 to help identify active clusters contributing to recent transmission. While large clusters originated >10 years ago, most continue to expand, particularly among young men. Enhanced prevention interventions to active clusters are planned to halt further propagation.