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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    • "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.
    PLoS ONE 02/2014; 9(2):e88512. DOI:10.1371/journal.pone.0088512 · 3.23 Impact Factor
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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.
    PLoS ONE 12/2013; 8(12):e80884. DOI:10.1371/journal.pone.0080884 · 3.23 Impact Factor
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    • "Compared to other studies we found that local transmission structure in Serbia is similar to the regions where MSM transmission predominates. Depending on the studied population, some studies revealed transmission structure of equal contribution to HIV epidemic through HIV spread among both heterosexual and MSM risk groups (Dennis et al., 2012). However, increase in the proportion of HIV-1 transmission through MSM networks has been reported in a number of studies throughout the world (Cuevas et al., 2009; Kouyos et al., 2010; Lewis et al., 2008; Mitsch et al., 2008; Paraschiv et al., 2012). "
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    ABSTRACT: Worldwide HIV-1 pandemic is becoming increasingly complex, with growing heterogeneity of subtypes and recombinant viruses. Previous studies have documented HIV-1 subtype B as the predominant one in Serbia, with limited presence and genetic diversity of non B subtypes. In recent years, MSM transmission has become the most frequently reported risk for HIV infection among newly diagnosed patients in Serbia, but very little is known of the network structure and dynamics of viral transmission in this and other risk groups. To gain insight about the HIV-1 subtypes distribution pattern as well as characteristics of HIV-1 transmission clusters in Serbia, we analyzed the genetic diversity of the pol gene segment in 221 HIV-1- infected patients sampled during 2002-2011. Subtype B was found to still be the most prevalent one in Serbia, accounting for over 90% of samples, while greater diversity of other subtypes was found than previously reported, including subtypes G, C, A, F, CRF01 and CRF02. In total, 41.3% of analyzed subtype B sequences were found associated in transmission clusters/network, that are highly related with MSM transmission route.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 06/2013; 19. DOI:10.1016/j.meegid.2013.06.015 · 3.02 Impact Factor
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