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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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Measures of disease progress in SHIV-infected rhesus macaques.The animals are divided into controllers (red) that survived longer than 600 days, and progressors (black) that were euthanized earlier due to severity of symptoms. (A) Longitudinal data for the CD4 T cells (in % of baseline) and (B) viral load.
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pone-0017180-g001: Measures of disease progress in SHIV-infected rhesus macaques.The animals are divided into controllers (red) that survived longer than 600 days, and progressors (black) that were euthanized earlier due to severity of symptoms. (A) Longitudinal data for the CD4 T cells (in % of baseline) and (B) viral load.

Mentions: In Figure 1 we show the longitudinal data for CD4+ T cell count in peripheral blood compared to baseline (A) and plasma viral load (B) for the 35 monkeys from the Shiver et al. study [13]. The baseline CD4 count was determined for each animal as the average value of two pre-infection time points. We divided all monkeys into two groups – those that survived for longer than 600 days (16 monkeys that we call “controllers”), and those that died or had to be euthanized earlier (19 monkeys that we call “progressors”). Out of 21 vaccinated animals, 15 controlled the infection and 6 were progressors (five DNA-based vaccines and one MVA), while only one of 14 unvaccinated animals controlled the infection. The timelines for the controllers are shown in red, while the black lines represent the progressors. Progressors had distinctly lower levels of CD4+ T cells at steady state and in the acute phase than controllers, less CD4 recovery after the acute phase than controllers, and higher viral set point and peak.


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

Petravic J, Davenport MP - PLoS ONE (2011)

Measures of disease progress in SHIV-infected rhesus macaques.The animals are divided into controllers (red) that survived longer than 600 days, and progressors (black) that were euthanized earlier due to severity of symptoms. (A) Longitudinal data for the CD4 T cells (in % of baseline) and (B) viral load.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017180-g001: Measures of disease progress in SHIV-infected rhesus macaques.The animals are divided into controllers (red) that survived longer than 600 days, and progressors (black) that were euthanized earlier due to severity of symptoms. (A) Longitudinal data for the CD4 T cells (in % of baseline) and (B) viral load.
Mentions: In Figure 1 we show the longitudinal data for CD4+ T cell count in peripheral blood compared to baseline (A) and plasma viral load (B) for the 35 monkeys from the Shiver et al. study [13]. The baseline CD4 count was determined for each animal as the average value of two pre-infection time points. We divided all monkeys into two groups – those that survived for longer than 600 days (16 monkeys that we call “controllers”), and those that died or had to be euthanized earlier (19 monkeys that we call “progressors”). Out of 21 vaccinated animals, 15 controlled the infection and 6 were progressors (five DNA-based vaccines and one MVA), while only one of 14 unvaccinated animals controlled the infection. The timelines for the controllers are shown in red, while the black lines represent the progressors. Progressors had distinctly lower levels of CD4+ T cells at steady state and in the acute phase than controllers, less CD4 recovery after the acute phase than controllers, and higher viral set point and peak.

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