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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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Related in: MedlinePlus

Characterization of gp120 sequence data set with respect to viral load and estimated time after infection. Line indicates the mean viral load as a function of time. Plasma used for viral load testing was collected as soon as possible following diagnostic tests confirming HIV-1 infection. The date of infection was defined as the midpoint between the last seronegative specimen and the first seropositive specimen.
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fig1: Characterization of gp120 sequence data set with respect to viral load and estimated time after infection. Line indicates the mean viral load as a function of time. Plasma used for viral load testing was collected as soon as possible following diagnostic tests confirming HIV-1 infection. The date of infection was defined as the midpoint between the last seronegative specimen and the first seropositive specimen.

Mentions: The estimated time of HIV-1 infection to first sampling ranged from 0 to 13 months with a mean time of infection of 109 ± 58 days. Thus, by the criteria of Fiebig et al. (2003), most of the sequences described in this report appear to represent stage V and VI infections. Time-course analysis of viral loads after HIV-1 infection (Clark et al. 1991; Daar et al. 1991) indicate the virus replicates to a very high level (105–106 virions/ml) within a few weeks of HIV-1 infection and then declines to a stable setpoint value. As expected, there was a significant decline in mean viral loads over time (fig. 1). However, we noted a significant compression of the data around 3 months postinfection. This appears to be an artifact of the 6-month interval scheduled between most clinic visits and the convention used to define the estimated day of infection (described in VAX004 Vaccine Trial Participants). Therefore, the estimated date of infection represents an overestimation, and the actual date of infection is earlier than indicated. Because there were approximately 20 infections with estimated dates of infection of 30 days or less, we suspect that these truly represent new and acute infections and should properly fall into Fieberg stage II–IV infections (Fiebig et al. 2003). It is likely that other early-stage infections occur in this cohort, but other assay methodologies will be required to identify them.


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)

Characterization of gp120 sequence data set with respect to viral load and estimated time after infection. Line indicates the mean viral load as a function of time. Plasma used for viral load testing was collected as soon as possible following diagnostic tests confirming HIV-1 infection. The date of infection was defined as the midpoint between the last seronegative specimen and the first seropositive specimen.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Characterization of gp120 sequence data set with respect to viral load and estimated time after infection. Line indicates the mean viral load as a function of time. Plasma used for viral load testing was collected as soon as possible following diagnostic tests confirming HIV-1 infection. The date of infection was defined as the midpoint between the last seronegative specimen and the first seropositive specimen.
Mentions: The estimated time of HIV-1 infection to first sampling ranged from 0 to 13 months with a mean time of infection of 109 ± 58 days. Thus, by the criteria of Fiebig et al. (2003), most of the sequences described in this report appear to represent stage V and VI infections. Time-course analysis of viral loads after HIV-1 infection (Clark et al. 1991; Daar et al. 1991) indicate the virus replicates to a very high level (105–106 virions/ml) within a few weeks of HIV-1 infection and then declines to a stable setpoint value. As expected, there was a significant decline in mean viral loads over time (fig. 1). However, we noted a significant compression of the data around 3 months postinfection. This appears to be an artifact of the 6-month interval scheduled between most clinic visits and the convention used to define the estimated day of infection (described in VAX004 Vaccine Trial Participants). Therefore, the estimated date of infection represents an overestimation, and the actual date of infection is earlier than indicated. Because there were approximately 20 infections with estimated dates of infection of 30 days or less, we suspect that these truly represent new and acute infections and should properly fall into Fieberg stage II–IV infections (Fiebig et al. 2003). It is likely that other early-stage infections occur in this cohort, but other assay methodologies will be required to identify them.

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