title: HIV-1 clade C infection and progressive disruption in the relationship between cortisol, DHEAS and CD4 cell numbers: a two-year follow-up study.
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 3beta-hydroxysteroid dehydrogenase (3beta-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 3beta-HSD activity for potential therapeutic application in HIV-1C infection.
authors: Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India. Seetharamaiah.Chittiprol@nationwidechildrens.org
authors: Seetharamaiah
authors: S
authors: Chittiprol
authors: Adarsh M
authors: AM
authors: Kumar
authors: K Taranath
authors: KT
authors: Shetty
authors: H Ravi
authors: HR
authors: Kumar
authors: P
authors: P
authors: Satishchandra
authors: R S Bhimasena
authors: RS
authors: Rao
authors: V
authors: V
authors: Ravi
authors: A
authors: A
authors: Desai
authors: D K
authors: DK
authors: Subbakrishna
authors: Mariamma
authors: M
authors: Philip
authors: K S
authors: KS
authors: Satish
authors: Mahendra
authors: M
authors: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects / Q000503:physiopathology; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone