HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers

A two-year follow-up study

Seetharamaiah Chittiprol, Adarsh Kumar, K. Taranath Shetty, H. Ravi Kumar, P. Satishchandra, R. S Bhimasena Rao, V. Ravi, A. Desai, D. K. Subbakrishna, Mariamma Philip, K. S. Satish, Mahendra Kumar

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: It is well established that there is mutual interaction between the neuroendocrines and immune systems and that the disturbance in any one system could affect the function of the other. While there is a large body of evidence suggesting negative impact of human immunodeficiency virus type 1B (HIV-1B) infection on both immune and neuroendocrine systems, the consequence of HIV-1 clade C infection (with structural differences from HIV-1B virus) on these systems is not clearly understood. Methods: We carried out a 2-year longitudinal study on plasma profile of adrenocorticosteroids, including cortisol and DHEAS and their relationship with declining CD4+ cell counts in neurologically asymptomatic HIV-C infected individuals (N = 84) in order to understand the impact of HIV-1 clade C infection on adrenocortical dysfunction and its relationship with the progressive decline in the cell mediated immunity. Results: We found that while plasma cortisol levels increased significantly at baseline in HIV-1C infected individuals compared to those in HIV-negative controls (HIV-1C+, 9.83 ± 0.39 vs controls, 8.04 ± 0.45; p < 0.01), there was a significant decrease in DHEAS in HIV-1C+ individuals, compared to that in HIV-negative controls (81.02 ± 4.9 vs 185.1 ± 12.03, p < 0.001), and consequently a significant increase in cortisol:DHEAS ratio in HIV-1 clade C infected persons (0.19 ± 0.002 vs control 0.058 ± 0.006; p < 0.001). Moreover, in HIV-1C infected individuals, there was a strong positive correlation between DHEAS and CD4 cells (r = 0.2; p < 0.05), and a strong negative correlation between cortisol, as well as cortisol:DHEAS ratio and CD4 cells (r = - 0.25; p < 0.01; and r = - 0.31; p < 0.001, respectively). Conclusions: These findings suggest the persistent and progressive adrenocortical dysfunction during the asymptomatic phase of HIV infection, and that the evaluation of increase in plasma cortisol, a decrease in DHEAS, and an increase in cortisol:DHEAS ratio may serve as important biomarkers preceding the impending down regulation of CD4 cell counts and progressive decline in the immune system function in HIV-1C infection. Furthermore, these findings may indicate the dysregulation of 3β-hydroxysteroid dehydrogenase (3β-HSD) activity, the enzyme involved in the biosynthesis of cortisol and DHEA through the pregnenolone-progesterone pathway, and that it may offer an opportunity for drug discovery targeting re-regulation of 3β-HSD activity for potential therapeutic application in HIV-1C infection.

Original languageEnglish
Pages (from-to)4-10
Number of pages7
JournalClinica Chimica Acta
Volume409
Issue number1-2
DOIs
StatePublished - Nov 3 2009

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Hydrocortisone
HIV-1
Cell Count
HIV
Infection
3-Hydroxysteroid Dehydrogenases
Viruses
HIV Infections
Immune system
Immune System
Neurosecretory Systems
Plasmas
CD4 Lymphocyte Count
Pregnenolone
Dehydroepiandrosterone
Biosynthesis
Biomarkers
Virus Diseases
Drug Discovery
Drug Delivery Systems

Keywords

  • Body mass index (BMI)
  • CD cell count
  • CD:CD ratio
  • Clade C
  • Cortisol
  • Cortisol:DHEAS (C/D) ratio
  • DHEAS
  • HAART
  • HIV-1

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers : A two-year follow-up study. / Chittiprol, Seetharamaiah; Kumar, Adarsh; Shetty, K. Taranath; Ravi Kumar, H.; Satishchandra, P.; Rao, R. S Bhimasena; Ravi, V.; Desai, A.; Subbakrishna, D. K.; Philip, Mariamma; Satish, K. S.; Kumar, Mahendra.

In: Clinica Chimica Acta, Vol. 409, No. 1-2, 03.11.2009, p. 4-10.

Research output: Contribution to journalArticle

Chittiprol, S, Kumar, A, Shetty, KT, Ravi Kumar, H, Satishchandra, P, Rao, RSB, Ravi, V, Desai, A, Subbakrishna, DK, Philip, M, Satish, KS & Kumar, M 2009, 'HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers: A two-year follow-up study', Clinica Chimica Acta, vol. 409, no. 1-2, pp. 4-10. https://doi.org/10.1016/j.cca.2009.06.032
Chittiprol, Seetharamaiah ; Kumar, Adarsh ; Shetty, K. Taranath ; Ravi Kumar, H. ; Satishchandra, P. ; Rao, R. S Bhimasena ; Ravi, V. ; Desai, A. ; Subbakrishna, D. K. ; Philip, Mariamma ; Satish, K. S. ; Kumar, Mahendra. / HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers : A two-year follow-up study. In: Clinica Chimica Acta. 2009 ; Vol. 409, No. 1-2. pp. 4-10.
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T1 - HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers

T2 - A two-year follow-up study

AU - Chittiprol, Seetharamaiah

AU - Kumar, Adarsh

AU - Shetty, K. Taranath

AU - Ravi Kumar, H.

AU - Satishchandra, P.

AU - Rao, R. S Bhimasena

AU - Ravi, V.

AU - Desai, A.

AU - Subbakrishna, D. K.

AU - Philip, Mariamma

AU - Satish, K. S.

AU - Kumar, Mahendra

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Y1 - 2009/11/3

N2 - Background: It is well established that there is mutual interaction between the neuroendocrines and immune systems and that the disturbance in any one system could affect the function of the other. While there is a large body of evidence suggesting negative impact of human immunodeficiency virus type 1B (HIV-1B) infection on both immune and neuroendocrine systems, the consequence of HIV-1 clade C infection (with structural differences from HIV-1B virus) on these systems is not clearly understood. Methods: We carried out a 2-year longitudinal study on plasma profile of adrenocorticosteroids, including cortisol and DHEAS and their relationship with declining CD4+ cell counts in neurologically asymptomatic HIV-C infected individuals (N = 84) in order to understand the impact of HIV-1 clade C infection on adrenocortical dysfunction and its relationship with the progressive decline in the cell mediated immunity. Results: We found that while plasma cortisol levels increased significantly at baseline in HIV-1C infected individuals compared to those in HIV-negative controls (HIV-1C+, 9.83 ± 0.39 vs controls, 8.04 ± 0.45; p < 0.01), there was a significant decrease in DHEAS in HIV-1C+ individuals, compared to that in HIV-negative controls (81.02 ± 4.9 vs 185.1 ± 12.03, p < 0.001), and consequently a significant increase in cortisol:DHEAS ratio in HIV-1 clade C infected persons (0.19 ± 0.002 vs control 0.058 ± 0.006; p < 0.001). Moreover, in HIV-1C infected individuals, there was a strong positive correlation between DHEAS and CD4 cells (r = 0.2; p < 0.05), and a strong negative correlation between cortisol, as well as cortisol:DHEAS ratio and CD4 cells (r = - 0.25; p < 0.01; and r = - 0.31; p < 0.001, respectively). Conclusions: These findings suggest the persistent and progressive adrenocortical dysfunction during the asymptomatic phase of HIV infection, and that the evaluation of increase in plasma cortisol, a decrease in DHEAS, and an increase in cortisol:DHEAS ratio may serve as important biomarkers preceding the impending down regulation of CD4 cell counts and progressive decline in the immune system function in HIV-1C infection. Furthermore, these findings may indicate the dysregulation of 3β-hydroxysteroid dehydrogenase (3β-HSD) activity, the enzyme involved in the biosynthesis of cortisol and DHEA through the pregnenolone-progesterone pathway, and that it may offer an opportunity for drug discovery targeting re-regulation of 3β-HSD activity for potential therapeutic application in HIV-1C infection.

AB - Background: It is well established that there is mutual interaction between the neuroendocrines and immune systems and that the disturbance in any one system could affect the function of the other. While there is a large body of evidence suggesting negative impact of human immunodeficiency virus type 1B (HIV-1B) infection on both immune and neuroendocrine systems, the consequence of HIV-1 clade C infection (with structural differences from HIV-1B virus) on these systems is not clearly understood. Methods: We carried out a 2-year longitudinal study on plasma profile of adrenocorticosteroids, including cortisol and DHEAS and their relationship with declining CD4+ cell counts in neurologically asymptomatic HIV-C infected individuals (N = 84) in order to understand the impact of HIV-1 clade C infection on adrenocortical dysfunction and its relationship with the progressive decline in the cell mediated immunity. Results: We found that while plasma cortisol levels increased significantly at baseline in HIV-1C infected individuals compared to those in HIV-negative controls (HIV-1C+, 9.83 ± 0.39 vs controls, 8.04 ± 0.45; p < 0.01), there was a significant decrease in DHEAS in HIV-1C+ individuals, compared to that in HIV-negative controls (81.02 ± 4.9 vs 185.1 ± 12.03, p < 0.001), and consequently a significant increase in cortisol:DHEAS ratio in HIV-1 clade C infected persons (0.19 ± 0.002 vs control 0.058 ± 0.006; p < 0.001). Moreover, in HIV-1C infected individuals, there was a strong positive correlation between DHEAS and CD4 cells (r = 0.2; p < 0.05), and a strong negative correlation between cortisol, as well as cortisol:DHEAS ratio and CD4 cells (r = - 0.25; p < 0.01; and r = - 0.31; p < 0.001, respectively). Conclusions: These findings suggest the persistent and progressive adrenocortical dysfunction during the asymptomatic phase of HIV infection, and that the evaluation of increase in plasma cortisol, a decrease in DHEAS, and an increase in cortisol:DHEAS ratio may serve as important biomarkers preceding the impending down regulation of CD4 cell counts and progressive decline in the immune system function in HIV-1C infection. Furthermore, these findings may indicate the dysregulation of 3β-hydroxysteroid dehydrogenase (3β-HSD) activity, the enzyme involved in the biosynthesis of cortisol and DHEA through the pregnenolone-progesterone pathway, and that it may offer an opportunity for drug discovery targeting re-regulation of 3β-HSD activity for potential therapeutic application in HIV-1C infection.

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KW - CD cell count

KW - CD:CD ratio

KW - Clade C

KW - Cortisol

KW - Cortisol:DHEAS (C/D) ratio

KW - DHEAS

KW - HAART

KW - HIV-1

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