High Prevalence and Onward Transmission of Non-Pandemic HIV-1 Subtype B Clades in Northern and Northeastern Brazilian Regions.
ABSTRACT: The Human immunodeficiency virus type-1 (HIV-1) epidemic in Brazil is mainly driven by the subtype B pandemic lineage (BPANDEMIC), while Caribbean non-pandemic subtype B clades (BCAR) seem to account for a very low fraction of HIV-infections in this country. The molecular characteristics of the HIV-1 subtype B strains disseminated in the Northern and Northeastern Brazilian regions, however, have not been explored so far. In this study, we estimate the prevalence of the HIV-1 BPANDEMIC and BCAR clades across different Brazilian regions and we reconstruct the spatiotemporal dynamics of dissemination of the major Brazilian BCAR clades. A total of 2,682 HIV-1 subtype B pol sequences collected from 21 different Brazilian states from the five country regions between 1998 and 2013 were analyzed. Maximum Likelihood phylogenetic analyses revealed that the BCAR strains reached 16 out 21 Brazilian states here analyzed. The BCAR clades comprise a low fraction (<10%) of subtype B infections in most Brazilian states analyzed, with exception of Roraima (41%), Amazonas (14%) and Maranhão (14%). Bayesian phylogeographic analyses indicate that BCAR strains originally from the Hispaniola and Trinidad and Tobago were introduced at multiple times into different states from all Brazilian regions and a few of those strains, probably introduced into Roraima, Maranhão and São Paulo between the late 1970s and the early 1980s, established secondary outbreaks in the Brazilian population. These results support that the HIV-1 subtype B epidemics in some Brazilian states from the Northern and Northeastern regions display a unique molecular pattern characterized by the high prevalence of BCAR lineages, which probably reflects a strong epidemiological link with the HIV-1 epidemics in the Caribbean region.
Project description:In the last decade a growing HIV/AIDS epidemic with increased incidence and AIDS-related mortality has been reported in Northern Brazil from which molecular data are scarce. Also, apparently healthy, adult blood donors, recently diagnosed with HIV-1 represent important sentinel populations for molecular studies. This cross-sectional study describes HIV-1 subtypes in blood donors from three reference public blood centers located in three States in Northern Brazil. HIV-1 pol sequencing (protease/PR, reverse transcriptase/RT) was performed on plasma samples of HIV-1 positive donors from HEMOAM, Manaus, Amazonas (n = 198), HEMERON, Porto Velho, Rondônia (n = 20) and HEMORAIMA, Boa Vista, Roraima (n = 9) collected from 2011-2017. HIV-1 subtypes were identified by REGA, phylogenetic inference; recombinant viruses were characterized by SIMPLOT. Young, single, males predominated, around half was first-time donors. Syphilis co-infection was detected in 17% (39 out of 227), 8% (18 out of 227) was anti-HBc positive. Subtype B represented ≥ 90% in Amazonas, Rondônia and Roraima, subtype C (3.1%) was found in Amazonas and Rondônia; subtype F1 (0.9%) and BF1 recombinants (5.3%) were only detected in Amazonas. Subtype B sequences from Amazonas (n = 179), Rondônia (n = 18) and Roraima (n = 9) were combined with viral strains representative of the BPANDEMIC (n = 300) and BCARIBBEAN/BCAR (n = 200) lineages. The BPANDEMIC lineage predominated (78%) although BCAR lineages were frequent in Roraima (56%) and Amazonas (22%). Subtype C and subtype F1 sequences identified here clustered within Brazilian CBR and F1BR lineages, respectively. Twelve BF1 mosaics showed 11 different recombination profiles: six were singleton unique-recombinant-forms/URFs, one displays a CRF28/29_BF-like recombinant pattern and the remaining four BF1 isolates branched with other Brazilian BF1 viruses previously described and may represent putative new CRF_BF1 from Northern Brazil. Our study shows a highly homogeneous molecular pattern with prevalent subtype B, followed by BF1, and sporadic subtype C and F1 in blood donors from the Northern region. Surveillance studies are important to monitor HIV-1 diversity which can reveal patterns of viral dissemination, especially in a highly endemic, remote and geographically isolated region as Northern Brazil.
Project description:Non-pandemic variants of the Human Immunodeficiency Virus Type 1 (HIV-1) subtype B accounts for a significant fraction of HIV infections in several Caribbean islands, Northeastern South American countries and the Northern Brazilian states of Roraima and Amazonas. In this paper, we used a comprehensive dataset of HIV-1 subtype B pol sequences sampled in Amazonas and Roraima between 2007 and 2017 to reconstruct the phylogeographic and demographic dynamics of the major HIV-1 subtype B non-pandemic Brazilian lineage, designated as BCAR-BR-I. Our analyses revealed that its origin could be traced to one of many viral introductions from French Guiana and Guyana into Northern Brazil, which probably occurred in the state of Amazonas around the late 1970s. The BCAR-BR-I clade was rapidly disseminated from Amazonas to Roraima, and the epidemic grew exponentially in these Northern Brazilian states during the 1980s and 1990s, coinciding with a period of economic and fast population growth in the region. The spreading rate of the BCAR-BR-I clade, however, seems to have slowed down since the early 2000s, despite the continued expansion of the HIV-1 epidemic in this region in the last decade.
Project description:The Human Immunodeficiency Virus Type I (HIV-1) subtype B comprises approximately 10% of all HIV infections in the world. The HIV-1 subtype B epidemic comprehends a pandemic variant (named BPANDEMIC) disseminated worldwide and non-pandemic variants (named BCAR) that are mostly restricted to the Caribbean. The goal of this work was the identification of amino acid signatures (AAs) characteristic to the BCAR and BPANDEMIC variants. To this end, we analyzed HIV-1 subtype B full-length (n = 486) and partial (n = 814) genomic sequences from the Americas classified within the BCAR and BPANDEMIC clades and reconstructed the sequences of their most recent common ancestors (MRCA). Analysis of contemporary HIV-1 sequences revealed 13 AAs between BCAR and BPANDEMIC variants (four on Gag, three on Pol, three on Rev, and one in Vif, Vpu, and Tat) of which only two (one on Gag and one on Pol) were traced to the MRCA. All AAs correspond to polymorphic sites located outside essential functional proteins domains, except the AAs in Tat. The absence of stringent AAs inherited from their ancestors between modern BCAR and BPANDEMIC variants support that ecological factors, rather than viral determinants, were the main driving force behind the successful spread of the BPANDEMIC strain.
Project description: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.
Project description:The HIV-1 subtype B epidemic in French Guiana and Suriname is characterized by the co-circulation of the globally disseminated "BPANDEMIC" lineage and of non-pandemic subtype B lineages of Caribbean origin (BCAR). To reconstruct the spatiotemporal pattern of spread of those viral lineages circulating in these two countries, a total of 361 HIV-1 subtype B pol sequences recovered from treatment-naive adult patients from French Guiana and Suriname between 2006 and 2012 were combined with BPANDEMIC and BCAR reference sequences. Major Guianese/Surinamese BPANDEMIC and BCAR lineages were identified by Maximum Likelihood phylogenetic analysis and the spatiotemporal and demographic parameters estimated using a Bayesian coalescent-based method. We detected four BCAR and three BPANDEMIC transmission chains of large size that together comprise most pandemic and non-pandemic subtype B sequences from French Guiana (?52%) and Suriname (?70%) here analyzed. These major lineages were probably introduced into French Guiana and Suriname from the Caribbean (BCAR) and North/South America (BPANDEMIC) between the middle 1970s and the late 1980s and spread among populations from both countries with roughly comparable demographic growth rates. We detected a significant trend for higher viral loads and higher proportion of homosexual/bisexual men among subjects infected with BPANDEMIC relative to BCAR strains in French Guiana. These results show that the HIV subtype B epidemic in French Guiana and Suriname has been driven by multiple active BCAR and BPANDEMIC transmission chains that arose since the middle 1970s onward and operate in both countries simultaneously. Although no significant differences in the epidemic potential of major BCAR and BPANDEMIC lineages were observed, relevant associations between the infecting subtype B lineage and epidemiological and clinical characteristics were detected in French Guiana.
Project description:Different explanations exist on how HIV-1 subtype B spread in Central America, but the role of Guatemala, the Central American country with the highest number of people living with the virus, in this scenario is unknown. We investigated the evolutionary history and spatiotemporal dynamics of HIV-1 subtype B in Guatemala. A total of 1,047 HIV-1 subtype B pol sequences, from newly diagnosed ART-naïve, HIV-infected Guatemalan subjects enrolled between 2011 and 2013 were combined with published subtype B sequences from other Central American countries (n = 2,101) and with reference sequences representative of the BPANDEMIC and BCAR lineages from the United States (n = 465), France (n = 344) and the Caribbean (n = 238). Estimates of evolutionary, demographic, and phylogeographic parameters were obtained from sequence data using maximum likelihood and Bayesian coalescent-based methods. The majority of Guatemalan sequences (98.9%) belonged to the BPANDEMIC clade, and 75.2% of these sequences branched within 10 monophyletic clades: four also included sequences from other Central American countries (BCAM-I to BCAM-IV) and six were mostly (>99%) composed by Guatemalan sequences (BGU clades). Most clades mainly comprised sequences from heterosexual individuals. Bayesian coalescent-based analyses suggested that BGU clades originated during the 1990s and 2000s, whereas BCAM clades originated between the late 1970s and mid 1980s. The major hub of dissemination of all BGU, and of BCAM-II, and BCAM-IV clades was traced to the Department of Guatemala, while the root location of BCAM-I and BCAM-III was traced to Honduras. Most Guatemalan clades experienced initial phases of exponential growth (0.23 and 3.6 year-1), followed by recent growth declines. Our observations suggest that the Guatemalan HIV-1 subtype B epidemic is driven by dissemination of multiple BPANDEMIC founder viral strains, some restricted to Guatemala and others widely disseminated in the Central American region, with Guatemala City identified as a major hub of viral dissemination. Our results also suggest the existence of different sub-epidemics within Guatemala for which different targeted prevention efforts might be needed.
Project description: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.
Project description:The HIV-1 epidemic in Brazil has spread towards the Northern country region, but little is known about HIV-1 subtypes and prevalence of HIV strains with resistance mutations to antiretrovirals in some of the Northern states. HIV-1 protease (PR) and reverse transcriptase (RT) sequences were obtained from 73 treatment-naive and -experienced subjects followed between 2013 and 2014 at a public health reference unit from Roraima, the northernmost Brazilian state. The most prevalent HIV-1 clade observed in the study population was the subtype B (91%), followed by subtype C (9%). Among 12 HIV-1 strains from treatment-naïve patients, only one had a transmitted drug resistance mutation for NNRTI. Among 59 treatment-experienced patients, 12 (20%) harbored HIV-1 strains with acquired drug resistance mutations (ADRM) that reduce the susceptibility to two classes of antiretroviral drugs (NRTI and NNRTI or NRTI and PI), and five (8%) harbored HIV-1 strains with ADRM that reduced susceptibility to only one class of antiretroviral drugs (NNRTI or PI). No patients harboring HIV strains with reduced susceptibility to all three classes of antiretroviral drugs were detected. A substantial fraction of treatment-experienced patients with (63%) and without (70%) ADRM had undetectable plasma viral loads (<40 copies/ml) at the time of sampling. Among treatment-experienced with plasma viral loads above 2,000 copies/ml, 44% displayed no ADRM. This data showed that the HIV-1 epidemic in Roraima displayed a much lower level of genetic diversity and a lower prevalence of ADRM than that described in other Brazilian states.
Project description:The human immunodeficiency virus-type 1 (HIV-1) subtype B has probably been circulating on the island of Hispaniola since the 1960s, but information about the early viral history on this Caribbean island is scarce. In this study, we reconstruct the dissemination dynamics of early divergent non-pandemic subtype B lineages (designated BCAR) on Hispaniola by analyzing a country-balanced dataset of HIV-1 BCAR pol sequences from Haiti (n = 103) and the Dominican Republic (n = 123). Phylogenetic analyses supported that BCAR strains from Haiti and the Dominican Republic were highly intermixed between each other, although the null hypothesis of completely random mixing was rejected. Bayesian phylogeographic analyses placed the ancestral BCAR virus in Haiti and the Dominican Republic with the same posterior probability support. These analyses estimate frequent viral transmissions between Haiti and the Dominican Republic since the early 1970s onwards, and the presence of local BCAR transmission networks in both countries before first AIDS cases was officially recognized. Demographic reconstructions point that the BCAR epidemic in Hispaniola grew exponentially until the 1990s. These findings support that the HIV-1 epidemics in Haiti and the Dominican Republic have been connected by a recurrent bidirectional viral flux since the initial phase, which poses a great challenge in tracing the geographic origin of the BCAR epidemic within Hispaniola using only genetic data. These data also reinforce the notion that prevention programs have successfully reduced the rate of new HIV-1 transmissions in Hispaniola since the end of the 1990s.
Project description:Previous studies indicate that the HIV-1 subtype C epidemic in southern Brazil was initiated by the introduction of a single founder strain probably originating from east Africa. However, the exact country of origin of such a founder strain as well as the origin of the subtype C viruses detected outside the Brazilian southern region remains unknown. HIV-1 subtype C pol sequences isolated in the southern, southeastern and central-western Brazilian regions (n = 209) were compared with a large number (n ~ 2,000) of subtype C pol sequences of African origin. Maximum-likelihood analyses revealed that most HIV-1 subtype C Brazilian sequences branched in a single monophyletic clade (CBR-I), nested within a larger monophyletic lineage characteristic of east Africa. Bayesian analyses indicate that the CBR-I clade most probably originated in Burundi and was introduced into the Paraná state (southern region) around the middle 1970s, after which it rapidly disseminated to neighboring regions. The states of Paraná and Santa Catarina have been the most important hubs of subtype C dissemination, and routine travel and spatial accessibility seems to have been the major driving forces of this process. Five additional introductions of HIV-1 subtype C strains probably originated in eastern (n = 2), southern (n = 2) and central (n = 1) African countries were detected in the Rio de Janeiro state (southeastern region). These results indicate a continuous influx of HIV-1 subtype C strains of African origin into Brazil and also unveil the existence of unrecognized transmission networks linking this country to east Africa.