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Simian-human immunodeficiency infection--is the course set in the acute phase?

Petravic J, Davenport MP - PLoS ONE (2011)

Bottom Line: We found that in most cases, the depletion of CD4+ T cells in chronic infection was consistent with the prediction from the acute CD4+ T cell loss.However, the animals with less than 3.3% of baseline CD4 T cells in the acute phase were approximately 20% more depleted late in the infection than expected based on constant level of virus control.This suggests that severe acute CD4 depletion indeed impairs the immune response.

View Article: PubMed Central - PubMed

Affiliation: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Sydney, Australia.

ABSTRACT
Identifying early predictors of infection outcome is important for the clinical management of HIV infection, and both viral load and CD4+ T cell level have been found to be useful predictors of subsequent disease progression. Very high viral load or extensively depleted CD4+ T cells in the acute phase often result in failure of immune control, and a fast progression to AIDS. It is usually assumed that extensive loss of CD4+ T cells in the acute phase of HIV infection prevents the establishment of robust T cell help required for virus control in the chronic phase. We tested this hypothesis using viral load and CD4+ T cell number of SHIV-infected rhesus macaques. In acute infection, the lowest level of CD4+ T cells was a good predictor of later survival; animals having less than 3.3% of baseline CD4+ T cells progressed to severe disease, while animals with more than 3.3% of baseline CD4+ T cells experienced CD4+ T cell recovery. However, it is unclear if the disease progression was caused by early depletion, or was simply a result of a higher susceptibility of an animal to infection. We derived a simple relationship between the expected number of CD4+ T cells in the acute and chronic phases for a constant level of host susceptibility or resistance. We found that in most cases, the depletion of CD4+ T cells in chronic infection was consistent with the prediction from the acute CD4+ T cell loss. However, the animals with less than 3.3% of baseline CD4 T cells in the acute phase were approximately 20% more depleted late in the infection than expected based on constant level of virus control. This suggests that severe acute CD4 depletion indeed impairs the immune response.

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Related in: MedlinePlus

Differential recovery is significantly positively correlated to CD4+ T cell preservation:(A) in the acute phase (Spearman r = 0.536, p = 0.0009); (B) in the chronic phase (Spearman r = 0.745, p<0.0001). Grey rectangles represent CD4+ T cell levels below the survival thresholds. If we consider only the points with CD4+ T cells above the survival thresholds (outside the grey rectangles), (A) in the acute phase the correlation is no more significant (Spearman r = 0.346, p = 0.1743), but (B) it is still significant in the chronic phase (Spearman r = 0.681, p = 0.0052)
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pone-0017180-g005: Differential recovery is significantly positively correlated to CD4+ T cell preservation:(A) in the acute phase (Spearman r = 0.536, p = 0.0009); (B) in the chronic phase (Spearman r = 0.745, p<0.0001). Grey rectangles represent CD4+ T cell levels below the survival thresholds. If we consider only the points with CD4+ T cells above the survival thresholds (outside the grey rectangles), (A) in the acute phase the correlation is no more significant (Spearman r = 0.346, p = 0.1743), but (B) it is still significant in the chronic phase (Spearman r = 0.681, p = 0.0052)

Mentions: The progressors, who have lower levels of CD4+ T cells both in acute and in chronic phase, recover less than expected in the chronic phase. This suggests that weaker recovery might be associated with the level of early CD4+ T cell depletion. In Figure 5 we plot the differential recovery against the acute CD4 level (Figure 5A) and CD4 level in the chronic phase (Figure 5B). In both cases there is a significant over-all positive correlation (Spearman r = 0.536, p = 0.0009 in the acute phase and Spearman r = 0.745, p<0.0001 in the chronic phase). However, the significance of the correlation of recovery with the acute CD4 level in Figure 5A heavily relies on the cluster of points at very low CD4 fraction belonging to progressors. If we remove this cluster of points with the acute CD4+ T cell level below 3.3% of baseline (the acute survival threshold in the grey rectangle) the positive correlation loses significance (Spearman r = 0.346, p = 0.1743). This may indicate that either there is indeed some damage caused by the loss of more than 96.7% CD4+ T cells in the acute phase, but that preservation of more than 3.3% CD4+ T cells might be sufficient for the maintenance of stable immune function.


Simian-human immunodeficiency infection--is the course set in the acute phase?

Petravic J, Davenport MP - PLoS ONE (2011)

Differential recovery is significantly positively correlated to CD4+ T cell preservation:(A) in the acute phase (Spearman r = 0.536, p = 0.0009); (B) in the chronic phase (Spearman r = 0.745, p<0.0001). Grey rectangles represent CD4+ T cell levels below the survival thresholds. If we consider only the points with CD4+ T cells above the survival thresholds (outside the grey rectangles), (A) in the acute phase the correlation is no more significant (Spearman r = 0.346, p = 0.1743), but (B) it is still significant in the chronic phase (Spearman r = 0.681, p = 0.0052)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040775&req=5

pone-0017180-g005: Differential recovery is significantly positively correlated to CD4+ T cell preservation:(A) in the acute phase (Spearman r = 0.536, p = 0.0009); (B) in the chronic phase (Spearman r = 0.745, p<0.0001). Grey rectangles represent CD4+ T cell levels below the survival thresholds. If we consider only the points with CD4+ T cells above the survival thresholds (outside the grey rectangles), (A) in the acute phase the correlation is no more significant (Spearman r = 0.346, p = 0.1743), but (B) it is still significant in the chronic phase (Spearman r = 0.681, p = 0.0052)
Mentions: The progressors, who have lower levels of CD4+ T cells both in acute and in chronic phase, recover less than expected in the chronic phase. This suggests that weaker recovery might be associated with the level of early CD4+ T cell depletion. In Figure 5 we plot the differential recovery against the acute CD4 level (Figure 5A) and CD4 level in the chronic phase (Figure 5B). In both cases there is a significant over-all positive correlation (Spearman r = 0.536, p = 0.0009 in the acute phase and Spearman r = 0.745, p<0.0001 in the chronic phase). However, the significance of the correlation of recovery with the acute CD4 level in Figure 5A heavily relies on the cluster of points at very low CD4 fraction belonging to progressors. If we remove this cluster of points with the acute CD4+ T cell level below 3.3% of baseline (the acute survival threshold in the grey rectangle) the positive correlation loses significance (Spearman r = 0.346, p = 0.1743). This may indicate that either there is indeed some damage caused by the loss of more than 96.7% CD4+ T cells in the acute phase, but that preservation of more than 3.3% CD4+ T cells might be sufficient for the maintenance of stable immune function.

Bottom Line: We found that in most cases, the depletion of CD4+ T cells in chronic infection was consistent with the prediction from the acute CD4+ T cell loss.However, the animals with less than 3.3% of baseline CD4 T cells in the acute phase were approximately 20% more depleted late in the infection than expected based on constant level of virus control.This suggests that severe acute CD4 depletion indeed impairs the immune response.

View Article: PubMed Central - PubMed

Affiliation: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Sydney, Australia.

ABSTRACT
Identifying early predictors of infection outcome is important for the clinical management of HIV infection, and both viral load and CD4+ T cell level have been found to be useful predictors of subsequent disease progression. Very high viral load or extensively depleted CD4+ T cells in the acute phase often result in failure of immune control, and a fast progression to AIDS. It is usually assumed that extensive loss of CD4+ T cells in the acute phase of HIV infection prevents the establishment of robust T cell help required for virus control in the chronic phase. We tested this hypothesis using viral load and CD4+ T cell number of SHIV-infected rhesus macaques. In acute infection, the lowest level of CD4+ T cells was a good predictor of later survival; animals having less than 3.3% of baseline CD4+ T cells progressed to severe disease, while animals with more than 3.3% of baseline CD4+ T cells experienced CD4+ T cell recovery. However, it is unclear if the disease progression was caused by early depletion, or was simply a result of a higher susceptibility of an animal to infection. We derived a simple relationship between the expected number of CD4+ T cells in the acute and chronic phases for a constant level of host susceptibility or resistance. We found that in most cases, the depletion of CD4+ T cells in chronic infection was consistent with the prediction from the acute CD4+ T cell loss. However, the animals with less than 3.3% of baseline CD4 T cells in the acute phase were approximately 20% more depleted late in the infection than expected based on constant level of virus control. This suggests that severe acute CD4 depletion indeed impairs the immune response.

Show MeSH
Related in: MedlinePlus