Multiple introductions and onward transmission of non-pandemic HIV-1 subtype B strains in North America and Europe.

Most HIV-1 subtype B infections in North America and Europe seem to have resulted from the expansion of a single pandemic lineage (BPANDEMIC) disseminated from the United States (US). Some non-pandemic subtype B strains of Caribbean origin (BCAR) may have also reached North America and Europe, but their epidemiological relevance in those regions remains largely unknown. Here we analyze a total of 20,045 HIV-1 subtype B pol sequences from the US, Canada, and Europe, to estimate the prevalence and to reconstruct the spatiotemporal dynamics of dissemination of HIV-1 BCAR strains in those regions. We find that BCAR strains were probably disseminated from the Caribbean into North America and Europe at multiple times since the early 1970s onwards. The BCAR strains reached the US, Canada and at least 16 different European countries, where they account for a very low fraction (<5%) of subtype B infections, with exception of the Czech Republic (7.7%). We also find evidence of the onward transmission of BCAR clades in the US, Canada, the Czech Republic, Germany, Italy, Spain and the UK, as well as short-distance spreading of BCAR lineages between neighboring European countries from Central and Western Europe, and long-distance dissemination between the US and Europe.

Phylogeny and Phylogeography of a Recent HIV-1 Subtype F Outbreak among Men Who Have Sex with Men in Spain Deriving from a Cluster with a Wide Geographic Circulation in Western Europe.

We recently reported the rapid expansion of an HIV-1 subtype F cluster among men who have sex with men (MSM) in the region of Galicia, Northwest Spain. Here we update this outbreak, analyze near full-length genomes, determine phylogenetic relationships, and estimate its origin. For this study, we used sequences of HIV-1 protease-reverse transcriptase and env V3 region, and for 17 samples, near full-length genome sequences were obtained. Phylogenetic analyses were performed via maximum likelihood. Locations and times of most recent common ancestors were estimated using Bayesian inference. Among samples analyzed by us, 100 HIV-1 F1 subsubtype infections of monophyletic origin were diagnosed in Spain, including 88 in Galicia and 12 in four other regions. Most viruses (n = 90) grouped in a subcluster (Galician subcluster), while 7 from Valladolid (Central Spain) grouped in another subcluster. At least 94 individuals were sexually-infected males and at least 71 were MSM. Seventeen near full-length genomes were uniformly of F1 subsubtype. Through similarity searches and phylogenetic analyses, we identified 18 viruses from four other Western European countries [Switzerland (n = 8), Belgium (n = 5), France (n = 3), and United Kingdom (n = 2)] and one from Brazil, from samples collected in 2005-2011, which branched within the subtype F cluster, outside of both Spanish subclusters, most of them corresponding to recently infected individuals. The most probable geographic origin and age of the Galician subcluster was Ferrol, Northwest Galicia, around 2007, while the Western European cluster probably emerged in Switzerland around 2002. In conclusion, a recently expanded HIV-1 subtype F cluster, the largest non-subtype B cluster reported in Western Europe, continues to spread among MSM in Spain; this cluster is part of a larger cluster with a wide geographic circulation in diverse Western European countries.

Phylodynamics of major HIV-1 subtype B pandemic clades circulating in Latin America.

OBJECTIVE: To obtain a comprehensive description of the evolutionary and demographic history of major HIV-1 subtype B pandemic (BPANDEMIC) clades circulating in Latin America. DESIGN: A total of 6789 HIV-1 subtype B pol sequences collected from seven different Latin American countries between 1990 and 2011 were combined with BPANDEMIC reference sequences (n = 500) from the United States and France. METHODS: Major BPANDEMIC clades were identified by maximum likelihood phylogenetic analysis with sequential pruning of ambiguously positioned taxa. Time scale and demographic reconstructions were performed using a Bayesian coalescent-based method. RESULTS: We identified 12 major BPANDEMIC monophyletic lineages mainly composed by Latin American sequences and that together comprise 36% of all subtype B sequences from the region here included. Four clades belong to two major regional lineages that comprise sequences from at least two neighboring countries, whereas the other eight clades were country-specific. The median age of major Latin American BPANDEMIC clades encompass a period of two decades (1968-1988), although most of them probably arose before the early 1980s. All major clades seem to have experienced an initial period of exponential growth, with median epidemic growth rates that range from 0.50 yearto 0.94 year, followed by a recent decline in growth rate. CONCLUSION: About one-third of HIV-1 subtype B infections in Latin America originated from the spread of a few BPANDEMIC founder strains probably introduced in the region since the late 1960s. Despite their initial successful dissemination, all major BPANDEMIC clades showed signs of subsequent epidemic stabilization.

Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries.

The HIV-1 subtype A variant dominating the HIV-1 epidemics in former Soviet Union (FSU) countries (A(FSU)) represents one of the major clades of the HIV-1 pandemic. This variant was reported to have begun spreading among injecting drug users (IDUs) in the Ukrainian city of Odessa in late 1994. Two competing hypotheses have been proposed on the ancestral origin of the A(FSU) variant, locating it either in the Democratic Republic of Congo (DRC) or in the Republic of Guinea (RG). The studies supporting these hypotheses employed phylogenetic analyses to identify HIV-1 sequences collected outside FSU countries ancestrally related to A(FSU). A different approach, based on Bayesian phylogenetic inference and coalescent-based population genetics, has been employed here to elucidate the ancestry of this HIV-1 variant and to improve our knowledge on its spread in FSU countries. The analyses were carried out using env (C2-V3-C3) and p24(gag) fragments of the HIV-1 genome. The inferred migration for the HIV-1 A(FSU) variant revealed only one significantly supported migration pathway from Africa to Eastern Europe, supporting the hypothesis of its origin in the DRC and estimating the upper limit of the migration of the ancestral virus from Africa around 1970. The support for an origin in the RG was negligible. The results supported the main role of Odessa as the epicenter of the A(FSU) epidemic, dating the tMRCA of the A(FSU) variant around 1984, ten years before its explosive expansion among IDUs. The estimated origin of the AFSU subcluster responsible for the IDU outbreak was also located in Odessa, with the estimated tMRCA around 1993. Statistically supported migration routes from Odessa to other cities of Ukraine, Russia, Kazakhstan, Uzbekistan and Belarus were also inferred by the Bayesian phylogeographic analysis. These results shed new light on the origin and spread of the HIV-1 A(FSU) variant.

Dissemination of nonpandemic Caribbean HIV-1 subtype B clades in Latin America.

OBJECTIVE: To estimate the prevalence of the HIV-1 subtype B pandemic (BPANDEMIC) and Caribbean (BCAR) clades in Latin America and to reconstruct the spatiotemporal dynamics of dissemination of the BCAR clades in the region. DESIGN: A total of 7654 HIV-1 subtype B pol sequences collected from 18 different Latin American countries between 1989 and 2011 were analyzed together with subtype B reference sequences representative of the BPANDEMIC (US/France = 300) and the BCAR (Caribbean = 279, Panama = 37) clades. METHODS: Phylogeographic and evolutionary parameters were estimated from sequence data using maximum likelihood and Bayesian coalescent-based methods. RESULTS: Nonpandemic BCAR strains were probably disseminated from the Caribbean islands of Hispaniola and Trinidad and Tobago into Latin America since the early 1970s. The BCAR strains reached nearly all countries from Latin America here analyzed and in some of them were spread locally, although their overall prevalence in the region is low. The BPANDEMIC clade comprises more than 90% of subtype B infections in most countries analyzed, with exception of Suriname, French Guyana and probably Guyana, where both BPANDEMIC and BCAR clades seem to circulate at a similar prevalence. CONCLUSION: This study demonstrates that nonpandemic subtype B lineages of Caribbean origin have been disseminated into Latin America shortly after the estimated introduction of subtype B in the continent. Despite their early dissemination, the BCAR strains account for a minor fraction of current HIV-1 subtype B infections in the region that are mainly driven by spreading of the globally disseminated BPANDEMIC clade.

Spatiotemporal dynamics of dissemination of non-pandemic HIV-1 subtype B clades in the Caribbean region.

The Human immunodeficiency virus type-1 (HIV-1) epidemic in the Caribbean region is mostly driven by subtype B; but information about the pattern of viral spread in this geographic region is scarce and different studies point to quite divergent models of viral dissemination. In this study, we reconstructed the spatiotemporal and population dynamics of the HIV-1 subtype B epidemic in the Caribbean. A total of 1,806 HIV-1 subtype B pol sequences collected from 17 different Caribbean islands between 1996 and 2011 were analyzed together with sequences from the United States (n = 525) and France (n = 340) included as control. Maximum Likelihood phylogenetic analyses revealed that HIV-1 subtype B infections in the Caribbean are driven by dissemination of the pandemic clade (BPANDEMIC) responsible for most subtype B infections across the world, and older non-pandemic lineages (BCAR) characteristics of the Caribbean region. The non-pandemic BCAR strains account for >40% of HIV-1 infections in most Caribbean islands; with exception of Cuba and Puerto Rico. Bayesian phylogeographic analyses indicate that BCAR strains probably arose in the island of Hispaniola (Haiti/Dominican Republic) around the middle 1960s and were later disseminated to Trinidad and Tobago and to Jamaica between the late 1960s and the early 1970s. In the following years, the BCAR strains were also disseminated from Hispaniola and Trinidad and Tobago to other Lesser Antilles islands at multiple times. The BCAR clades circulating in Hispaniola, Jamaica and Trinidad and Tobago appear to have experienced an initial phase of exponential growth, with mean estimated growth rates of 0.35-0.45 year(-1), followed by a more recent stabilization since the middle 1990s. These results demonstrate that non-pandemic subtype B lineages have been widely disseminated through the Caribbean since the late 1960s and account for an important fraction of current HIV-1 infections in the region.