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Lack of evidence for changing virulence of HIV-1 in North America.

Herbeck JT, Gottlieb GS, Li X, Hu Z, Detels R, Phair J, Rinaldo C, Jacobson LP, Margolick JB, Mullins JI - PLoS ONE (2008)

Bottom Line: Several long-term cohort studies and in-vitro fitness assays have resulted in inconsistent reports on changes in HIV-1 virulence, including reports of decreasing, stable, and increasing virulence over the course of the AIDS pandemic.No statistically significant association was found between year of seroconversion and "set point" plasma viral load (at approximately 9 months after seroconversion: slope = -0.004 log(10) copies/mL/year, p = 0.76; at approximately 15 months: slope = -0.005 log(10) copies/mL/year, p = 0.71), CD4 cell count after seroconversion (at approximately 9 months: slope = -0.112 cells/microL/year, p = 0.22; at approximately 15 months: slope = -0.047 cells/microL/year, p = 0.64), or rate of CD4 cell decline over the first three years after seroconversion (slope = -0.010 cells/ul/yr(2), p = 0.88).The lack of significant trends from 1984 to 2005 in these prognostic markers of HIV disease progression suggests no major change in HIV-1 virulence over the AIDS pandemic in MSM in the US.

View Article: PubMed Central - PubMed

Affiliation: University of Washington School of Medicine, Seattle, Washington, USA.

ABSTRACT

Background: Several long-term cohort studies and in-vitro fitness assays have resulted in inconsistent reports on changes in HIV-1 virulence, including reports of decreasing, stable, and increasing virulence over the course of the AIDS pandemic. We tested the hypothesis of changing HIV-1 virulence by examining trends in prognostic clinical markers of disease progression from 1984 to 2005 among nearly 400 antiretroviral-naïve participants in the United States Multicenter AIDS Cohort Study (MACS), a longitudinal study of HIV infection in men who have sex with men (MSM).

Methodology/principal findings: Because clinical AIDS endpoints could not be used (due to antiretroviral therapies and prophylaxis), three prognostic markers of disease progression were used as proxies for HIV-1 virulence: plasma viral RNA load and CD4+ T cell count at "set point" (between approximately 9 and approximately 15 months after seroconversion), and rate of CD4 cell decline within three years after seroconversion. We performed multivariate analyses of the association between these markers and seroconversion year, with covariates including MACS site, race/ethnic group, seroconversion age, and CCR5Delta32 status. No statistically significant association was found between year of seroconversion and "set point" plasma viral load (at approximately 9 months after seroconversion: slope = -0.004 log(10) copies/mL/year, p = 0.76; at approximately 15 months: slope = -0.005 log(10) copies/mL/year, p = 0.71), CD4 cell count after seroconversion (at approximately 9 months: slope = -0.112 cells/microL/year, p = 0.22; at approximately 15 months: slope = -0.047 cells/microL/year, p = 0.64), or rate of CD4 cell decline over the first three years after seroconversion (slope = -0.010 cells/ul/yr(2), p = 0.88).

Conclusions/significance: The lack of significant trends from 1984 to 2005 in these prognostic markers of HIV disease progression suggests no major change in HIV-1 virulence over the AIDS pandemic in MSM in the US.

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CD4+ T cell levels through time.A) Boxplot for the mean of square-root transformed CD4+ T-cell count at second and third seropositive visits (∼9 and ∼15 months after estimated date of seroconversion) by calendar period of seroconversion. Boxes are defined as in the legend to Figure 1. B) Relationship between the mean of square-root transformed CD4+ T-cell count at second and third seropositive visits and calendar year of seroconversion. Three solid lines are the fitted regression line and its 95% confidence bands from univariate linear regression (note that slope estimates reported in manuscript text are from multivariate analysis).
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pone-0001525-g002: CD4+ T cell levels through time.A) Boxplot for the mean of square-root transformed CD4+ T-cell count at second and third seropositive visits (∼9 and ∼15 months after estimated date of seroconversion) by calendar period of seroconversion. Boxes are defined as in the legend to Figure 1. B) Relationship between the mean of square-root transformed CD4+ T-cell count at second and third seropositive visits and calendar year of seroconversion. Three solid lines are the fitted regression line and its 95% confidence bands from univariate linear regression (note that slope estimates reported in manuscript text are from multivariate analysis).

Mentions: In the analysis of the mean of the second and third seropositive visits (if data was available for both visits, only one visit if only visit had data available), we found no significant temporal trend in viral load (n = 384, slope = −0.005 log10 copies/mL/year, p = 0.66) (Table 3) (Figure 1). We found a slight decreasing trend in square-root transformed CD4 cell count (n = 409, slope = −0.138 cells/µL/year, p = 0.10) (Table 3) (Figure 2). These trends translate to decreases of of ∼0.1 log10 copies/mL in viral load set point and ∼7 cells for the CD4 cell count over the 20 year study period; neither of these values is clinically significant.


Lack of evidence for changing virulence of HIV-1 in North America.

Herbeck JT, Gottlieb GS, Li X, Hu Z, Detels R, Phair J, Rinaldo C, Jacobson LP, Margolick JB, Mullins JI - PLoS ONE (2008)

CD4+ T cell levels through time.A) Boxplot for the mean of square-root transformed CD4+ T-cell count at second and third seropositive visits (∼9 and ∼15 months after estimated date of seroconversion) by calendar period of seroconversion. Boxes are defined as in the legend to Figure 1. B) Relationship between the mean of square-root transformed CD4+ T-cell count at second and third seropositive visits and calendar year of seroconversion. Three solid lines are the fitted regression line and its 95% confidence bands from univariate linear regression (note that slope estimates reported in manuscript text are from multivariate analysis).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211407&req=5

pone-0001525-g002: CD4+ T cell levels through time.A) Boxplot for the mean of square-root transformed CD4+ T-cell count at second and third seropositive visits (∼9 and ∼15 months after estimated date of seroconversion) by calendar period of seroconversion. Boxes are defined as in the legend to Figure 1. B) Relationship between the mean of square-root transformed CD4+ T-cell count at second and third seropositive visits and calendar year of seroconversion. Three solid lines are the fitted regression line and its 95% confidence bands from univariate linear regression (note that slope estimates reported in manuscript text are from multivariate analysis).
Mentions: In the analysis of the mean of the second and third seropositive visits (if data was available for both visits, only one visit if only visit had data available), we found no significant temporal trend in viral load (n = 384, slope = −0.005 log10 copies/mL/year, p = 0.66) (Table 3) (Figure 1). We found a slight decreasing trend in square-root transformed CD4 cell count (n = 409, slope = −0.138 cells/µL/year, p = 0.10) (Table 3) (Figure 2). These trends translate to decreases of of ∼0.1 log10 copies/mL in viral load set point and ∼7 cells for the CD4 cell count over the 20 year study period; neither of these values is clinically significant.

Bottom Line: Several long-term cohort studies and in-vitro fitness assays have resulted in inconsistent reports on changes in HIV-1 virulence, including reports of decreasing, stable, and increasing virulence over the course of the AIDS pandemic.No statistically significant association was found between year of seroconversion and "set point" plasma viral load (at approximately 9 months after seroconversion: slope = -0.004 log(10) copies/mL/year, p = 0.76; at approximately 15 months: slope = -0.005 log(10) copies/mL/year, p = 0.71), CD4 cell count after seroconversion (at approximately 9 months: slope = -0.112 cells/microL/year, p = 0.22; at approximately 15 months: slope = -0.047 cells/microL/year, p = 0.64), or rate of CD4 cell decline over the first three years after seroconversion (slope = -0.010 cells/ul/yr(2), p = 0.88).The lack of significant trends from 1984 to 2005 in these prognostic markers of HIV disease progression suggests no major change in HIV-1 virulence over the AIDS pandemic in MSM in the US.

View Article: PubMed Central - PubMed

Affiliation: University of Washington School of Medicine, Seattle, Washington, USA.

ABSTRACT

Background: Several long-term cohort studies and in-vitro fitness assays have resulted in inconsistent reports on changes in HIV-1 virulence, including reports of decreasing, stable, and increasing virulence over the course of the AIDS pandemic. We tested the hypothesis of changing HIV-1 virulence by examining trends in prognostic clinical markers of disease progression from 1984 to 2005 among nearly 400 antiretroviral-naïve participants in the United States Multicenter AIDS Cohort Study (MACS), a longitudinal study of HIV infection in men who have sex with men (MSM).

Methodology/principal findings: Because clinical AIDS endpoints could not be used (due to antiretroviral therapies and prophylaxis), three prognostic markers of disease progression were used as proxies for HIV-1 virulence: plasma viral RNA load and CD4+ T cell count at "set point" (between approximately 9 and approximately 15 months after seroconversion), and rate of CD4 cell decline within three years after seroconversion. We performed multivariate analyses of the association between these markers and seroconversion year, with covariates including MACS site, race/ethnic group, seroconversion age, and CCR5Delta32 status. No statistically significant association was found between year of seroconversion and "set point" plasma viral load (at approximately 9 months after seroconversion: slope = -0.004 log(10) copies/mL/year, p = 0.76; at approximately 15 months: slope = -0.005 log(10) copies/mL/year, p = 0.71), CD4 cell count after seroconversion (at approximately 9 months: slope = -0.112 cells/microL/year, p = 0.22; at approximately 15 months: slope = -0.047 cells/microL/year, p = 0.64), or rate of CD4 cell decline over the first three years after seroconversion (slope = -0.010 cells/ul/yr(2), p = 0.88).

Conclusions/significance: The lack of significant trends from 1984 to 2005 in these prognostic markers of HIV disease progression suggests no major change in HIV-1 virulence over the AIDS pandemic in MSM in the US.

Show MeSH
Related in: MedlinePlus