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.

HIV-1 genetic diversity and antiretroviral drug resistance among individuals from Roraima state, northern Brazil

“…Notably, among the 73 patients included in our study and that attended the Public Health Central Laboratory in Boa Vista, two patients were from St. Helena de Uairén and one patient from Lethem, reflecting the intense human mobility across the Roraima borders with Venezuela and Guyana. Consistent with this, we recently described a singular high prevalence of non-pandemic subtype B variants of Caribbean origin in Roraima [36]. These data suggest that the HIV-1 epidemic in Roraima is more closely related to epidemics in neighboring South American countries (Venezuela and Guyana) than to epidemics in other Brazilian regions.…”

The HIV-1 Subtype B Epidemic in French Guiana and Suriname Is Driven by Ongoing Transmissions of Pandemic and Non-pandemic Lineages

“…Subtype B is the predominant HIV-1 lineage circulating in French Guiana ( Kazanji et al, 2001 ; Darcissac et al, 2016 ) and Suriname ( Abdoel Wahid et al, 2016 ); but in sharp contrast to other continental American countries where the epidemic is mostly driven by the globally disseminated “B PANDEMIC ” lineage, the subtype B epidemic in French Guiana and Suriname is driven by transmission of both B PANDEMIC and of non-pandemic subtype B lineages characteristic of the Caribbean region (“B CAR ” lineages) ( Cabello et al, 2015 ). This epidemiological pattern resembles that described in several Caribbean islands (Haiti, the Dominican Republic, Jamaica, The Bahamas and the Lesser Antilles) ( Cabello et al, 2014 ) and in the Northern Brazilian state of Roraima ( Divino et al, 2016 ). Previous phylogenetic analyses revealed that a substantial fraction (30–95%) of subtype B infections in Latin American and Caribbean countries resulted from the expansion of a few local (or regional) B PANDEMIC and B CAR founder strains ( Delatorre and Bello, 2013 ; Cabello et al, 2014 , 2015 ; Mendoza et al, 2014 ; Mir et al, 2015 ; Divino et al, 2016 ), thus supporting a great geographic compartmentalization of the HIV-1 subtype B epidemic in those regions.…”

“…This epidemiological pattern resembles that described in several Caribbean islands (Haiti, the Dominican Republic, Jamaica, The Bahamas and the Lesser Antilles) ( Cabello et al, 2014 ) and in the Northern Brazilian state of Roraima ( Divino et al, 2016 ). Previous phylogenetic analyses revealed that a substantial fraction (30–95%) of subtype B infections in Latin American and Caribbean countries resulted from the expansion of a few local (or regional) B PANDEMIC and B CAR founder strains ( Delatorre and Bello, 2013 ; Cabello et al, 2014 , 2015 ; Mendoza et al, 2014 ; Mir et al, 2015 ; Divino et al, 2016 ), thus supporting a great geographic compartmentalization of the HIV-1 subtype B epidemic in those regions.…”

“…To reconstruct spatiotemporal dynamics and identify the most probable source location of major B CAR Guianese/Surinamese lineages here identified, we selected B CAR sequences from the major Caribbean islands with high prevalence of non-pandemic strains and B CAR sequences from neighboring South American countries, including: all B CAR sequences from Hispaniola and sequences of major B CAR lineages circulating in Trinidad and Tobago (B CAR-TT ), Jamaica (B CAR-JM-I ), Brazil (B CAR-BR-I and B CAR-BR-II ), and Guyana (B CAR-GY ) identified in previous studies ( Cabello et al, 2014 , 2015 ; Divino et al, 2016 ) ( Supplementary Table S3 ). Similarly, to identify the most probable source location of major B PANDEMIC Guianese/Surinamese lineages we selected a subset of B PANDEMIC reference sequences from regions with the highest human flux from/to French Guiana and Suriname (the Caribbean, South America, Central America, North America, and Europe).…”

“…HIV-1 B CAR and B PANDEMIC pol sequences from French Guiana and Suriname were next aligned with B CAR sequences from the Caribbean and Brazil and with B PANDEMIC sequences from the United States (US), France, the Netherlands, and Northern Brazil characterized previously ( Cabello et al, 2014 , 2015 , 2016 ; Divino et al, 2016 ) ( Supplementary Table S2 ). Sequences were subjected to ML analyses as described above and Guianese and Surinamese B CAR and B PANDEMIC transmission clusters were defined as highly supported ( aLRT ≥ 0.85) monophyletic clusters mostly (>90%) composed by sequences from these countries.…”