The dispersal of HIV-1 subtype B (HIV-1B) is a reflection of the movement of human populations in response to social, political, and geographical issues. The initial dissemination of HIV-1B outside Africa seems to have included the passive involvement of human populations from the Caribbean in spreading the virus to the United States. However, the exact pathways taken during the establishment of the pandemic in the Americas remain unclear. Here, we propose a geographical scenario for the dissemination of HIV-1B in the Americas, based on phylogenetic and genetic statistical analyses of 313 available sequences of the pol gene from 27 countries. Maximum likelihood and Bayesian inference methods were used to explore the phylogenetic relationships between HIV-1B sequences, and molecular variance estimates were analyzed to infer the genetic structure of the viral population. We found that the initial dissemination and subsequent spread of subtype B in the Americas occurred via a single introduction event in the Caribbean around 1964 (1950–1967). Phylogenetic trees present evidence of several primary outbreaks in countries in South America, directly seeded by the Caribbean epidemic. Cuba is an exception insofar as its epidemic seems to have been introduced from South America. One clade comprising isolates from different countries emerged in the most-derived branches, reflecting the intense circulation of the virus throughout the American continents. Statistical analysis supports the genetic compartmentalization of the virus among the Americas, with a close relationship between the South American and Caribbean epidemics. These findings reflect the complex establishment of the HIV-1B pandemic and contribute to our understanding between the migration process of human populations and virus diffusion.
Entry of HIV-1 into a host cell is a multi-step process, with the viral envelope gp120 and gp41 acting sequentially to mediate the viral attachment, CD4 binding, coreceptor binding, and fusion of the viral and host membranes. The emerging class of antiretroviral agents, collectively known as entry inhibitors, interfere in some of these steps. However, viral diversity has implications for possible differential responses to entry inhibitors, since envelope is the most variable of all HIV genes. Different HIV genetic forms carry in their genomes genetic signatures and polymorphisms that could alter the structure of viral proteins which are targeted by drugs, thus impairing antiretroviral binding and efficacy. This review will examine current research that describes subtype differences in envelope at the genetic level and the effects of mutations on the efficacy of current entry inhibitors.
Background: Although most HIV-1 infections in Brazil are due to subtype
B, Southern Brazil has a high prevalence of subtype C and recombinant forms, such as
CRF31_BC. This study assessed the impact of viral diversity on clinical progression
in a cohort of newly diagnosed HIV-positive patients.
Methods: From July/2004 to December/2005, 135 HIV-infected patients were
recruited. The partial pol region was subtyped by phylogeny. A
generalized estimating equation (GEE) model was used to examine the relationship
between viral subtype, CD4+ T cell count and viral load levels before antiretroviral
therapy. Hazard ratio (Cox regression) was used to evaluate factors associated with
viral suppression (viral load < 50 copies/mL at six months).
Results: Main HIV-1 subtypes included B (29.4%), C (28.2%), and CRF31_BC
(23.5%). Subtypes B and C showed a similar trend in CD4+ T cell decline. Comparison
of non-B (C and CRF31_BC) and B subtypes revealed no significant difference in the
proportion of patients with viral suppression at six months (week 24). Higher CD4+ T
cell count and lower viral load were independently associated with viral
suppression.
Conclusion: No significant differences were found between subtypes;
however, lower viral load and higher CD4+ T cell count before therapy were associated
with better response.
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