HIV and AIDSHow does vitamin D work?

The beneficial action of vitamin D on patients with HIV or AIDS is primarily through the action of 1,25(OH)2D in activating vitamin D receptors (VDRs). VDRs regulate expression of at least 1000 genes, up-regulating about two-thirds and down-regulating one-third. Several studies have reported risk of HIV or progression to AIDS for various VDR alleles (varieties)1234.

1,25(OH)2D induces production of cathelicidin and defensins, which have antimicrobial and antiendotoxin effects extending to both bacteria and viruses56. See, also, the section on influenza.

Vitamin D also reduces the risk of many other diseases including many types of cancer, cardiovascular disease, bacterial and viral infections, diabetes mellitus, osteoporosis, etc., through mechanisms discussed in the other sections of this site.

On the other hand, several studies have identified mechanisms for increased risk for HIV/AIDS with respect to serum 25(OH)D or 1,25(OH)2D levels. 1,25(OH)2D levels are generally directly correlated with 25(OH)D levels up to 25(OH)D levels of 75 nmol/L, then flat after that7. One effect is that 1,25(OH)2D facilitates HIV replication8910. However, cathelicidin, induced by 1,25(OH)2D, has been found to inhibit HIV replication11. Thus, further research is required to sort out the relative contributions of these effects.

The human apolipoprotein B mRNA-editing enzyme-catalytic polipeptide-like-3G (APOBECG3) has raised special interest as interfering agent of HIV dissemination12. T-helper-1 (Th1) cells have more APOEBECG3 than Th2 cells13. 1,25(OH)2D shifts the Th1-Th2 balance towards Th214. Thus, this shift may reduce the risk of HIV/AIDS.

Page last edited: 09 May 2011

References

  1. Alagarasu, K. Selvaraj, P. Swaminathan, S. Narendran, G. Narayanan, P. R. 5′ regulatory and 3′ untranslated region polymorphisms of vitamin D receptor gene in south Indian HIV and HIV-TB patients. J Clin Immunol. 2009 Mar; 29 (2): 196-204.
  2. de la Torre, M. S. Torres, C. Nieto, G. Vergara, S. Carrero, A. J. Macias, J. Pineda, J. A. Caruz, A. Fibla, J. Vitamin D receptor gene haplotypes and susceptibility to HIV-1 infection in injection drug users. J Infect Dis. 2008 Feb 1; 197 (3): 405-10.
  3. Nieto, G. Barber, Y. Rubio, M. C. Rubio, M. Fibla, J. Association between AIDS disease progression rates and the Fok-I polymorphism of the VDR gene in a cohort of HIV-1 seropositive patients. J Steroid Biochem Mol Biol. 2004 May; 89-90 (1-5): 199-207.
  4. Torres, C. de la Torre, M. S. Garcia-Moruja, C. Carrero, A. J. Del Monte, M. T. Fibla, J. Caruz, A. Immunophenotype of Vitamin D Receptor Polymorphism Associated to Risk of HIV-1 Infection and Rate of Disease Progression. Curr HIV Res. 2010 Sep 1; 8 (6): 487-92.
  5. Gombart, A. F. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol. 2009 Nov; 41151-65.
  6. White, J. H. Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future. J Steroid Biochem Mol Biol. 2010 Jul; 121 (1-2): 234-8.
  7. Rejnmark, L. Vestergaard, P. Heickendorff, L. Mosekilde, L. Plasma 1,25(OH)2D levels decrease in postmenopausal women with hypovitaminosis D. Eur J Endocrinol. 2008 Apr; 158 (4): 571-6.
  8. Biswas, P. Mengozzi, M. Mantelli, B. Delfanti, F. Brambilla, A. Vicenzi, E. Poli, G. 1,25-Dihydroxyvitamin D3 upregulates functional CXCR4 human immunodeficiency virus type 1 coreceptors in U937 minus clones: NF-kappaB-independent enhancement of viral replication. J Virol. 1998 Oct; 72 (10): 8380-3.
  9. Nevado, J. Tenbaum, S. P. Castillo, A. I. Sanchez-Pacheco, A. Aranda, A. Activation of the human immunodeficiency virus type I long terminal repeat by 1 alpha,25-dihydroxyvitamin D3. J Mol Endocrinol. 2007 Jun; 38 (6): 587-601.
  10. Pauza, C. D. Kornbluth, R. Emau, P. Richman, D. D. Deftos, L. J. Vitamin D3 compounds regulate human immunodeficiency virus type 1 replication in U937 monoblastoid cells and in monocyte-derived macrophages. J Leukoc Biol. 1993 Feb; 53 (2): 157-64.
  11. Bergman, P. Walter-Jallow, L. Broliden, K. Agerberth, B. Soderlund, J. The antimicrobial peptide LL-37 inhibits HIV-1 replication. Curr HIV Res. 2007 Jul; 5 (4): 410-5.
  12. Yamashita, T. Nomaguchi, M. Miyake, A. Uchiyama, T. Adachi, A. Status of APOBEC3G/F in cells and progeny virions modulated by Vif determines HIV-1 infectivity. Microbes Infect. 2010 Feb; 12 (2): 166-71.
  13. Vetter, M. L. Johnson, M. E. Antons, A. K. Unutmaz, D. D’Aquila, R. T. Differences in APOBEC3G expression in CD4+ T helper lymphocyte subtypes modulate HIV-1 infectivity. PLoS Pathog. 2009 Feb; 5 (2): e1000292.
  14. Cantorna, M. T. Mahon, B. D. D-hormone and the immune system. J Rheumatol Suppl. 2005 Sep; 7611-20.