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Phylogenetic Investigation of a Statewide HIV-1 Epidemic Reveals Ongoing and Active Transmission Networks Among Men Who Have Sex With Men.

ABSTRACT: BACKGROUND:Molecular epidemiological evaluation of HIV-1 transmission networks can elucidate behavioral components of transmission that can be targets for intervention. METHODS:We combined phylogenetic and statistical approaches using pol sequences from patients diagnosed between 2004 and 2011 at a large HIV center in Rhode Island, following 75% of the state's HIV population. Phylogenetic trees were constructed using maximum likelihood, and putative transmission clusters were evaluated using latent class analyses to determine association of cluster size with underlying demographic/behavioral characteristics. A logistic growth model was used to assess intracluster dynamics over time and predict "active" clusters that were more likely to harbor undiagnosed infections. RESULTS:Of the 1166 HIV-1 subtype B sequences, 31% were distributed among 114 statistically supported, monophyletic clusters (range: 2-15 sequences/cluster). Sequences from men who have sex with men (MSM) formed 52% of clusters. Latent class analyses demonstrated that sequences from recently diagnosed (2008-2011) MSM with primary HIV infection (PHI) and other sexually transmitted infections (STIs) were more likely to form larger clusters (odds ratio: 1.62-11.25, P < 0.01). MSM in clusters were more likely to have anonymous partners and meet partners at sex clubs and pornographic stores. Four large clusters with 38 sequences (100% male, 89% MSM) had a high probability of harboring undiagnosed infections and included younger MSM with PHI and STIs. CONCLUSIONS:In this first large-scale molecular epidemiological investigation of HIV-1 transmission in New England, sexual networks among recently diagnosed MSM with PHI and concomitant STIs contributed to the ongoing transmission. Characterization of transmission dynamics revealed actively growing clusters, which may be targets for intervention.

SUBMITTER: Chan PA

PROVIDER: S-EPMC4624575 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Phylogenetic Investigation of a Statewide HIV-1 Epidemic Reveals Ongoing and Active Transmission Networks Among Men Who Have Sex With Men.

Chan Philip A PA Hogan Joseph W JW Huang Austin A DeLong Allison A Salemi Marco M Mayer Kenneth H KH Kantor Rami R

Journal of acquired immune deficiency syndromes (1999) 20151201 4

<h4>Background</h4>Molecular epidemiological evaluation of HIV-1 transmission networks can elucidate behavioral components of transmission that can be targets for intervention.<h4>Methods</h4>We combined phylogenetic and statistical approaches using pol sequences from patients diagnosed between 2004 and 2011 at a large HIV center in Rhode Island, following 75% of the state's HIV population. Phylogenetic trees were constructed using maximum likelihood, and putative transmission clusters were eval ...[more]

PMID: 26258569

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Project description:BackgroundYunnan has the greatest share of reported human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) cases in China. In recent years, HIV prevalence and incidence remained stubbornly high in men who have sex with men (MSM). To follow the dynamics of the HIV-1 epidemic among MSM, HIV-1 genetic characteristics and genetic transmission networks were investigated.MethodsBlood samples from 190 newly diagnosed HIV-1 cases among MSM were continuously collected at fixed sites from January 2013 to December 2015 in Kunming City, Yunnan Province. Partial gag, pol and env genes were sequenced and used for phylogenetic and genotypic drug resistance analyses. The genetic characteristics of the predominant HIV-1 strains were analyzed by the Bayesian Markov Chain Monte Carlo (MCMC) method. The genetic transmission networks were identified with a genetic distance of 0.03 substitutions/site and 90% bootstrap support.ResultsAmong the 190 HIV-1 positive MSM reported during 2013-2105, various genotypes were identified, including CRF01_AE (45.3%), CRF07_BC (35.8%), unique recombinant forms (URFs) (11.6%), CRF08_BC (3.2%), CRF55_01B (2.1%), subtype B (1.6%) and CRF59_01B (0.5%). The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially from approximately 2001-2010 and 2005-2009, respectively. Genetic transmission networks were constructed with 308 pol sequences from MSM diagnosed during 2010-2015. Of the 308 MSM, 109 (35.4%) were identified in 38 distinct clusters. Having multiple male partners was associated with a high probability of identification in the genetic transmission networks. Of the 38 clusters, 27 (71.1%) contained individuals diagnosed in different years. Of the 109 individuals in the networks, 26 (23.9%) had ≥2 potential transmission partners (≥2 links). The proportion of MSM with ≥2 links was higher among those diagnosed from 2010-2012. The constituent ratios of their potential transmission partners by areas showed no significant difference among MSM from Kunming, other cities in Yunnan and other provinces. Additionally, surveillance drug resistance mutations (SDRMs) were identified in 5% of individuals.ConclusionThis study revealed the various HIV-a genotypes circulating among MSM in Kunming. MSM with more partners were more easily detected in transmission networks, and early-diagnosed MSM remained active in transmission networks. These findings suggested that the routine interventions should be combined with HIV testing and linkage to care and early antiretroviral therapy among HIV-positive MSM.

Project description:BackgroundThe HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains.Methods and findingsAs of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ?10 ATHENA sequences were selected, with a local support value ? 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters.ConclusionsThe resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.

Dataset Information

Phylogenetic Investigation of a Statewide HIV-1 Epidemic Reveals Ongoing and Active Transmission Networks Among Men Who Have Sex With Men.

Publications

Phylogenetic Investigation of a Statewide HIV-1 Epidemic Reveals Ongoing and Active Transmission Networks Among Men Who Have Sex With Men.

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