Phylogenetic insights into regional HIV transmission

aDivision of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA bDepartment of Infection, University College London, London, UK cDepartment of Epidemiology, University of North Carolina, Chapel Hill dCenter for Molecular Biology and Pathology, Laboratory Corporation of America, Research Triangle Park, North Carolina, USA.
AIDS (London, England) (Impact Factor: 5.55). 06/2012; 26(14):1813-22. DOI: 10.1097/QAD.0b013e3283573244
Source: PubMed


: Despite prevention efforts, new HIV diagnoses continue in the southern United States, where the epidemic is characterized by significant racial/ethnic disparities. We integrated phylogenetic analyses with clinical data to reveal trends in local HIV transmission.
: Cross-sectional analysis of 1671 HIV-infected individuals each with one B-subtype pol sequence obtained during chronic (82%; UNC Center for AIDS Research Clinical Cohort) or acute/recent (18%; Duke/UNC Acute HIV Consortium) infection.
: Phylogenies were inferred using neighbor joining to select related sequences then confirmed with Bayesian methods. We characterized transmission clusters (clades n ≥ 3 sequences supported by posterior probabilities = 1) by factors including race/ethnicity and transmission risk. Factors associated with cluster membership were evaluated for newly diagnosed patients.
: Overall, 72% were men, 59% black and 39% men who have sex with men (MSM). A total of 557 (33%) sequences grouped in either 108 pairs (n = 216) or 67 clusters (n = 341). Clusters ranged from three to 36 (median 4) members. Composition was delineated primarily by race, with 28% exclusively black, and to a lesser extent by risk group. Both MSM and heterosexuals formed discrete clusters, although substantial mixing was observed. In multivariable analysis, patients with age 30 years or less (P = 0.009), acute infection (P = 0.02), local residence (P = 0.002) and transmitted drug resistance (P = 0.02) were more likely to be cluster members, whereas Latinos were less likely (P < 0.001).
: Integration of molecular, clinical and demographic data offers a unique view into the structure of local transmission networks. Clustering by black race, youth and transmitted drug resistance and inability to identify Latino clusters will inform prevention, testing and linkage to care strategies.

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    • "p = 0.16) (30). Recent studies have suggested that newly diagnosed HIV-positive patients should cluster predominantly with other recently diagnosed HIV-positive[6,8,12,27282932,33]and indicate that transmission occurs early after infection. Debate continues about the possible predominant role of recently infected patients in the dynamics of the HIV epidemics. "
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    ABSTRACT: To relate socio-demographic and virological information to phylogenetic clustering in HIV infected patients in a limited geographical area and to evaluate the role of recently infected individuals in the spread of HIV. HIV-1 pol sequences from newly diagnosed and treatment-naive patients receiving follow-up between 2008 and 2011 by physicians belonging to a health network in Paris were used to build a phylogenetic tree using neighbour-joining analysis. Time since infection was estimated by immunoassay to define recently infected patients (very early infected presenters, VEP). Data on socio-demographic, clinical and biological features in clustered and non-clustered patients were compared. Chains of infection structure was also analysed. 547 patients were included, 49 chains of infection containing 108 (20%) patients were identified by phylogenetic analysis. analysis. Eighty individuals formed pairs and 28 individuals were belonging to larger clusters. The median time between two successive HIV diagnoses in the same chain of infection was 248 days [CI = 176-320]. 34.7% of individuals were considered as VEP, and 27% of them were included in chains of infection. Multivariable analysis showed that belonging to a cluster was more frequent in VEP and those under 30 years old (OR: 3.65, 95 CI 1.49-8.95, p = 0.005 and OR: 2.42, 95% CI 1.05-5.85, p = 0.04 respectively). The prevalence of drug resistance was not associated with belonging to a pair or a cluster. Within chains, VEP were not grouped together more than chance predicted (p = 0.97). Most newly diagnosed patients did not belong to a chain of infection, confirming the importance of undiagnosed or untreated HIV infected individuals in transmission. Furthermore, clusters involving both recently infected individuals and longstanding infected individuals support a substantial role in transmission of the latter before diagnosis.
    Full-text · Article · Aug 2015 · PLoS ONE
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    • "With the collection of HIV genetic sequences from newly infected individuals and sociodemographic information for partner counseling and referral services, new opportunities have developed for the merger of genetics, geography and epidemiology. Spatial molecular epidemiology has the potential to illuminate patterns of HIV transmission, and of TDR variants in particular, indicating populations and places where surveillance and interventions might best be targeted [24]–[26]. In particular, spatial molecular epidemiology can answer questions about whether urban areas act as reservoirs for rural HIV infection, or whether circulating strains of HIV differ between rural and urban areas. "
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    ABSTRACT: Transmission of HIV continues in the United States (US), despite prevention efforts aimed at education and treatment. Concurrently, drug resistance in HIV, particularly in patients being infected with HIV for the first time, poses a threat to the continued success of treatment for HIV positive individuals. In North Carolina, nearly one in five individuals with acute HIV infection (AHI) is infected with a drug-resistant strain, a phenomenon known as transmitted drug resistance (TDR). Few studies of AHI or TDR take into account both the spatial aspects of residence at time of infection and the genetic characteristics of the viruses, and questions remain about how viruses are transmitted across space and the rural-urban divide. Using AHI strains from North Carolina, we examined whether differences exist in the spatial patterns of AHI versus AHI with TDR, as well as whether the genetic characteristics of these HIV infections vary by rural-urban status and across Health Service Areas. The highest amounts of TDR were detected in persons under age 30, African Americans, and men who have sex with men (MSM) - similar to the populations where the highest numbers of AHI without TDR are observed. Nearly a quarter of patients reside in rural areas, and there are no significant differences between rural and urban residence among individuals infected with drug resistant or drug susceptible viruses. We observe similar levels of genetic distance between HIV found in rural and urban areas, indicating that viruses are shared across the rural-urban divide. Genetic differences are observed, however, across Health Service Areas, suggesting that local areas are sites of genetic differentiation in viruses being transmitted to newly infected individuals. These results indicate that future efforts to prevent HIV transmission need to be spatially targeted, focusing on local-level transmission in risky populations, in addition to statewide anti- HIV efforts.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "In addition, Bayesian maximum clade credibility (MCC) trees were constructed using BEAST 1.7 [16] to determine the posterior probability values for each network in subtype B, CRF01_AE and CRF51_01B. As previously described elsewhere, transmission network is defined as a network consisting of at least 3 isolates from different individuals [17] of the same geographical (i.e country) origin [18], and a phylogenetic clade supported by bootstrap value of more than 90% and Bayesian posterior probability value of 1.0 at the tree node [17], [19], [20]. "
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    ABSTRACT: HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 - 2629), gp120 (HXB2: 6942 - 7577) and gp41 (HXB2: 7803 - 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 - 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.
    Full-text · Article · Dec 2013 · PLoS ONE
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