Limits...
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.

Show MeSH

Related in: MedlinePlus

Differential recovery in progressors and controllers.We defined the “differential recovery” as the difference between the actual recovery and the amount of recovery expected if the immune response were constant. The differential recovery in progressors was significantly lower than in controllers (Mann-Whitney p<0.0001).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3040775&req=5

pone-0017180-g004: Differential recovery in progressors and controllers.We defined the “differential recovery” as the difference between the actual recovery and the amount of recovery expected if the immune response were constant. The differential recovery in progressors was significantly lower than in controllers (Mann-Whitney p<0.0001).

Mentions: When the data points appear below the theoretical curves in Figures 3A or 3B, this means that the animals had fewer CD4+ T cells in the chronic phase than expected from the acute phase. We can see that most animals (with the exception of five controllers) do worse than expected in the long run – most points are below the theoretical curves in Figure 3A and 3B. In order to quantify how much less the animals recover on average after the acute CD4 loss, we calculate the “differential recovery” – the difference between the actual recovery (T*-Tmin)/T0 and the amount of recovery expected if the immune response were constant (as estimated from the model). We obtain the overall median differential recovery of −16.9%, meaning that over all, the animals do worse than expected by 16.9%. Progressors do worse than expected by (median) 18.8%, while controllers do worse by (median) 3.9%, which is significantly better than progressors (Figure 4, Mann-Whitney p<0.0001).


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

Petravic J, Davenport MP - PLoS ONE (2011)

Differential recovery in progressors and controllers.We defined the “differential recovery” as the difference between the actual recovery and the amount of recovery expected if the immune response were constant. The differential recovery in progressors was significantly lower than in controllers (Mann-Whitney p<0.0001).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017180-g004: Differential recovery in progressors and controllers.We defined the “differential recovery” as the difference between the actual recovery and the amount of recovery expected if the immune response were constant. The differential recovery in progressors was significantly lower than in controllers (Mann-Whitney p<0.0001).
Mentions: When the data points appear below the theoretical curves in Figures 3A or 3B, this means that the animals had fewer CD4+ T cells in the chronic phase than expected from the acute phase. We can see that most animals (with the exception of five controllers) do worse than expected in the long run – most points are below the theoretical curves in Figure 3A and 3B. In order to quantify how much less the animals recover on average after the acute CD4 loss, we calculate the “differential recovery” – the difference between the actual recovery (T*-Tmin)/T0 and the amount of recovery expected if the immune response were constant (as estimated from the model). We obtain the overall median differential recovery of −16.9%, meaning that over all, the animals do worse than expected by 16.9%. Progressors do worse than expected by (median) 18.8%, while controllers do worse by (median) 3.9%, which is significantly better than progressors (Figure 4, Mann-Whitney p<0.0001).

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