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Phylodynamics of HIV-1 from a phase-III AIDS vaccine trial in North America.

Pérez-Losada M, Jobes DV, Sinangil F, Crandall KA, Posada D, Berman PW - Mol. Biol. Evol. (2009)

Bottom Line: The estimated time of emergence of HIV-1 subtype B was 1966-1970.Despite the fact that the number of AIDS cases has decreased in North America since the early 90s, HIV-1 genetic diversity seems to have remained almost constant over time.This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines.

View Article: PubMed Central - PubMed

Affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Vairão, Portugal. mlosada323@gmail.com

ABSTRACT
In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1 vaccine (AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1 infection from North America and the Netherlands. A total of 368 individuals became infected with HIV-1 during the trial. The envelope glycoprotein gene (gp120) from the HIV-1 subtype B viruses infecting 349 patients was sequenced from clinical samples taken as close as possible to the time of diagnosis, rendering a final data set of 1,047 sequences (1,032 from North America and 15 from the Netherlands). Here, we used these data in combination with other sequences available in public databases to assess HIV-1 variation as a function of vaccination treatment, geographic region, race, risk behavior, and viral load. Viral samples did not show any phylogenetic structure for any of these factors, but individuals with different viral loads showed significant differences (P = 0.009) in genetic diversity. The estimated time of emergence of HIV-1 subtype B was 1966-1970. Despite the fact that the number of AIDS cases has decreased in North America since the early 90s, HIV-1 genetic diversity seems to have remained almost constant over time. This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines.

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Maximum likelihood phylogenetic inference of North American HIV-1 subtype B population structure based on the VAX004NA data set. Branch lengths are shown proportional to the amount of change along the branches. Clades supported by bootstrap proportions ≥70% or posterior probabilities ≥0.95 in the Bayesian tree are shown in bold. Only one clone per patient is represented for simplicity.
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fig2: Maximum likelihood phylogenetic inference of North American HIV-1 subtype B population structure based on the VAX004NA data set. Branch lengths are shown proportional to the amount of change along the branches. Clades supported by bootstrap proportions ≥70% or posterior probabilities ≥0.95 in the Bayesian tree are shown in bold. Only one clone per patient is represented for simplicity.

Mentions: GTR+Γ+I (Tavaré 1986) was chosen as the best-fit model for both the VAX004NA and VAX004NA-LAGB data sets and for all their corresponding codon-position partitions. The initial phylogenetic analyses focused on investigating the quality of the VAX004NA data set. As expected, the three clone sequences collected per patient clustered together and were not interdispersed with sequences from other individuals. Although, in general, both ML and Bayesian phylogenetic analyses did not reveal population structuring, 17 well-supported small clades (bootstrap proportions ≥70% or posterior probabilities ≥0.95) were observed (fig. 2). These could be transmission linkages where individuals infected each other or were infected by a common partner. Eleven of these clades grouped patients from different geographic areas, but the other six clustered individuals from the same area and gender of which five were also from the same race. Because HIV-1 infection occurs primarily in well-defined risk groups, these types of linkages are likely to be observed in studies of this nature. Unfortunately, because information on partner relationships was restricted, we could not confirm the epidemiological history of these potential transmission chains. The phylogenetic trees did not show any obvious clustering of individuals based on treatment, geographic region, race, risk, or viral load (fig. 2). In fact, in all cases, individuals within each factor seemed to be randomly distributed across the gene trees.


Phylodynamics of HIV-1 from a phase-III AIDS vaccine trial in North America.

Pérez-Losada M, Jobes DV, Sinangil F, Crandall KA, Posada D, Berman PW - Mol. Biol. Evol. (2009)

Maximum likelihood phylogenetic inference of North American HIV-1 subtype B population structure based on the VAX004NA data set. Branch lengths are shown proportional to the amount of change along the branches. Clades supported by bootstrap proportions ≥70% or posterior probabilities ≥0.95 in the Bayesian tree are shown in bold. Only one clone per patient is represented for simplicity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806245&req=5

fig2: Maximum likelihood phylogenetic inference of North American HIV-1 subtype B population structure based on the VAX004NA data set. Branch lengths are shown proportional to the amount of change along the branches. Clades supported by bootstrap proportions ≥70% or posterior probabilities ≥0.95 in the Bayesian tree are shown in bold. Only one clone per patient is represented for simplicity.
Mentions: GTR+Γ+I (Tavaré 1986) was chosen as the best-fit model for both the VAX004NA and VAX004NA-LAGB data sets and for all their corresponding codon-position partitions. The initial phylogenetic analyses focused on investigating the quality of the VAX004NA data set. As expected, the three clone sequences collected per patient clustered together and were not interdispersed with sequences from other individuals. Although, in general, both ML and Bayesian phylogenetic analyses did not reveal population structuring, 17 well-supported small clades (bootstrap proportions ≥70% or posterior probabilities ≥0.95) were observed (fig. 2). These could be transmission linkages where individuals infected each other or were infected by a common partner. Eleven of these clades grouped patients from different geographic areas, but the other six clustered individuals from the same area and gender of which five were also from the same race. Because HIV-1 infection occurs primarily in well-defined risk groups, these types of linkages are likely to be observed in studies of this nature. Unfortunately, because information on partner relationships was restricted, we could not confirm the epidemiological history of these potential transmission chains. The phylogenetic trees did not show any obvious clustering of individuals based on treatment, geographic region, race, risk, or viral load (fig. 2). In fact, in all cases, individuals within each factor seemed to be randomly distributed across the gene trees.

Bottom Line: The estimated time of emergence of HIV-1 subtype B was 1966-1970.Despite the fact that the number of AIDS cases has decreased in North America since the early 90s, HIV-1 genetic diversity seems to have remained almost constant over time.This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines.

View Article: PubMed Central - PubMed

Affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Vairão, Portugal. mlosada323@gmail.com

ABSTRACT
In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1 vaccine (AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1 infection from North America and the Netherlands. A total of 368 individuals became infected with HIV-1 during the trial. The envelope glycoprotein gene (gp120) from the HIV-1 subtype B viruses infecting 349 patients was sequenced from clinical samples taken as close as possible to the time of diagnosis, rendering a final data set of 1,047 sequences (1,032 from North America and 15 from the Netherlands). Here, we used these data in combination with other sequences available in public databases to assess HIV-1 variation as a function of vaccination treatment, geographic region, race, risk behavior, and viral load. Viral samples did not show any phylogenetic structure for any of these factors, but individuals with different viral loads showed significant differences (P = 0.009) in genetic diversity. The estimated time of emergence of HIV-1 subtype B was 1966-1970. Despite the fact that the number of AIDS cases has decreased in North America since the early 90s, HIV-1 genetic diversity seems to have remained almost constant over time. This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines.

Show MeSH
Related in: MedlinePlus