Phylogenetic and geospatial evaluation of HIV-1 subtype diversity at the largest HIV center in Rhode Island

摘要

Individuals infected with HIV-1 non-B subtypes are understudied in the United States. Their characterization may augment prevention and treatment interventions. We examined the regional molecular epidemiology of non-B subtypes using a combined phylogenetic and geospatial approach. HIV-1 pol sequences and clinical data obtained for routine clinical care were aggregated from 2004 to 2011 at the largest HIV center in Rhode Island. Subtyping was performed by neighbor-joining and maximum-likelihood phylogeny and compared across eight commonly used tools (HIVdb, REGA, RIP, NCBI, Geno2Pheno, EuResist, jpHMM and STAR) using proportional odds ordinal regression. Individuals with non-B subtypes were characterized according to demographics and risk factors for infection, intra-subtype clustering by maximum- likelihood phylogeny, and geospatial hotspot analysis using Getis-Ord Gi* statistics. Of 1277 unique sequences, phylogenetic subtyping demonstrated 8.3% (N = 106, 95% CI 6.8-10%) non-B subtypes and circulating recombinant forms (CRFs): CRF02_AG = 46; A = 15; C = 15; CRF01_AE = 6; CRF06_CPX = 5; CRF14_BG = 5; G = 3; CRF43_02G = 3; D = 3; CRF24_BG = 3; CRF11_CPX = 1; F1 = 1. Compared to phylogeny, Geno2Pheno was the most concordant (86% exact match) followed by REGA (85%), EuResist (85%) and STAR (82%). Of 106 individuals with non-B subtypes, 50% were male, 71% acquired infection through heterosexual transmission; 76%, were born in Africa, 6% Southeast Asia, 5% the United States, 3% Central America, 1% Europe, and 9% unknown. Eighty percent of CRF02_AG, 93% of A and 87% of C sequences were from African-born individuals. Twenty-two percent of non-B subtypes formed transmission clusters, including a significant number of younger individuals with perinatally-acquired infection. Geospatial analyses revealed hotspots of B and non-B subtypes in the state capital with a more concentrated focus among non-B subtypes. Molecular examination of regional HIV diversity revealed a larger than expected non-subtype B infected population, mostly born in Africa, with low ongoing regional transmission. Phylogenetic and geospatial characterization of infection clusters is helpful to identify targets for treatment and prevention interventions. (C) 2014 Elsevier B.V. All rights reserved.