Advertisement
The Body: The Complete HIV/AIDS Resource
Follow Us Follow Us on Facebook Follow Us on Twitter Download Our App
Professionals >> Visit The Body PROThe Body en Espanol
Read Now: TheBodyPRO.com Covers AIDS 2014
  
  • Email Email
  • Comments Comments
  • Printable Single-Page Print-Friendly
  • Glossary Glossary
  • PDF PDF

Vitamin D Linked to Survival in HIV

December 23, 2010

Although vitamin D is classified as a vitamin, it behaves as a hormone within the body. Using sunlight and cholesterol, the body makes vitamin D in the skin. Vitamin D is then transported to the liver, where it is converted into vitamin D2, and then the kidneys, where it is converted into its active form called vitamin D3 (1,25-dihydroxy vitamin D3).

The precise roles(s) of vitamin D in the body are unclear. Certainly it helps the body absorb calcium from food and helps in bone formation. But many cells of the body, particularly those of the immune system, have receptors for vitamin D, so some scientists suspect that this substance may play a role in several health conditions.

Some European researchers consider the following vitamin D levels in the blood to be something that requires medical attention:

  • less than 30 ng/ml (75 mmol/l) -- low
  • less than 10 ng/ml (25 nmol/l) -- deficient
Advertisement

Observational studies in HIV-negative people suggest that less-than-normal levels of vitamin D in the blood may be linked to thin bones, increased risk for cancer, tuberculosis, cardiovascular disease, kidney dysfunction, type 2 diabetes and death.

Observational studies in HIV-positive people have found that vitamin D deficiency is common, particularly among people with dark skin living in temperate countries, such as Canada, and even among those in tropical countries where sunny days are common. Some researchers have found that the problems linked to vitamin D deficiency among HIV-negative people are strikingly similar to the co-morbidities (thinning bones, type 2 diabetes, kidney dysfunction, cardiovascular disease, and so on) that are increasingly being recognized in some HIV-positive people.

Researchers affiliated with the EuroSIDA database have been collecting health-related information for many years from HIV-positive people and decided to investigate vitamin D deficiency and factors associated with it. Out of 5,000 people, they chose about 2,000 whose vitamin D levels were available from assessments done by one laboratory at Hôpital Necker in Paris, France.


Results

The study team focused on 1,985 people whose samples were associated with other data in its database.

In general, there was no association between vitamin D and these factors:

  • CD4+ count
  • viral load
  • use or not of ART

However, the research team noticed that White participants tended to have higher levels of vitamin D in their blood than people of colour. Also, injection drug users (IDUs) tended to have lower levels of vitamin D than non-IDUs.

For every 10-year increase in the age of a person in the study, there was an increase of 12% relative risk for having a vitamin D deficiency.


Results -- Survival

There were a total of 188 deaths among the study participants. Death rates differed by vitamin D levels as follows:

  • severe vitamin D deficiency (12 ng/ml or lower) -- 11% of participants died
  • moderate levels of vitamin D deficiency (between 12 and 20 ng/ml) -- 7% of participants died
  • mild deficiency (more than 20 ng/ml) -- 6% of participants died

The differences between deaths among participants with severe vitamin D deficiency compared to deaths that occurred in participants with more moderate or mild vitamin D deficiency were statistically significant.


Results -- AIDS-Related Infections and Complications

In general, the greater the deficiency of vitamin D, the more likely participants were to develop AIDS-related complications:

  • severe vitamin D deficiency (12 ng/ml or lower) -- 10% of participants developed AIDS
  • moderate levels of vitamin D deficiency (between 12 and 20 ng/ml) -- 6% of participants developed AIDS
  • mild deficiency (more than 20 ng/ml) -- 5% of participants developed AIDS

The differences between AIDS-related infections and complications among participants with severe vitamin D deficiency compared to the number that occurred in participants with more moderate or mild vitamin D deficiency were statistically significant.

There was a similar trend in the distribution of non-AIDS-related events but this did not achieve statistical significance.


Why Were These Associations Found?

Vitamin D levels have historically been linked to poverty, so the EuroSIDA group may indeed have correctly linked vitamin D deficiency to poor survival. However, it is possible that the real cause of death may have nothing directly to do with vitamin D levels but instead be linked to other associated factors. For instance, income has previously been linked to reduced survival among HIV-positive people. It is possible that low vitamin D levels could be a surrogate marker for poverty, at least in some cases.

Depending on the severity of their addiction, IDUs may prioritize getting and using substances over habits linked to healthy living. Therefore, IDUs may have vitamin D deficiency (along with other nutrient deficiencies) though the cause(s) of their death may have nothing to do with vitamin D (such as violence, suicide, drug overdose, bacterial infections, cardiac dysfunction).

The relationship between body weight and height (body mass index, or BMI) was not apparently taken into account in the present EuroSIDA analysis. This may be important because vitamin D is stored in fat and other studies have found that overweight and obese people tend to have less-than-normal levels of vitamin D in the blood. It is possible that some of the deaths that occurred in the present study were due to being overweight or obese rather than vitamin D deficient.

Preliminary ongoing analyses from the EuroSIDA cohort suggest that people who take protease inhibitor-based ART tend to have higher vitamin D levels. However, more research needs to be done to see if this finding is linked to better health and longer survival.


Why the Uncertainty?

Because this was an observational study, confounding or channeling bias can inadvertently occur when interpreting the results, so the results must be taken with a degree of caution. Moreover, the study was based on just one measurement of vitamin D, so altogether, firmly linking cause and effect in this analysis is fraught with difficulty.

Larger observational studies have found that vitamin D deficiency has been linked to an increased risk of death among HIV-negative people, particularly from cardiovascular disease, so perhaps the EuroSIDA group has found something important. However, the large size of the EuroSIDA dataset suggests the possibility that low levels of vitamin D may be linked to poorer health in some HIV-positive people.


Clarity Ahead

Data analysis from a randomized controlled trial, such as those done by the United States government-funded ACTG, is now underway to assess stored blood samples for vitamin D levels and to try to understand the effect(s) of different ART regimens on this vitamin. Also, EuroSIDA researchers are conducting an intervention study where vitamin D supplements are given to some HIV-positive people and monitoring is being done to observe any benefit(s).

For now, vitamin D remains an intriguing subject for research. Until firm conclusions can be drawn from robustly designed studies, it is best to guide the intake of vitamin D based on laboratory testing of vitamin D levels in the blood.


References

  1. Viard JP, Souberbielle JC, Kirk O, et al. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study. In: Program and abstracts of the 12th International Workshop on Adverse Drug Reactions and Co-morbidities in HIV, 4-6 November 2010, London, UK. Abstract 021.
  2. Haug CJ, Aukrust P, Haug E, et al. Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis. Journal of Clinical Endocrinology and Metabolism. 1998 Nov;83(11):3832-8.
  3. Conrado T, Miranda-Filho Dde B, Bandeira F. Vitamin D deficiency in HIV-infected individuals: one more risk factor for bone loss and cardiovascular disease? Arquivos Brasileiros de Endocrinologia e Metabologia. 2010 Mar;54(2):118-22.
  4. Paul TV, Asha HS, Thomas N, et al. Hypovitaminosis D and bone mineral density in human immunodeficiency virus-infected men from India, with or without antiretroviral therapy. Endocrine Practice. 2010 Jul-Aug;16(4):547-53.
  5. Wasserman P, Rubin DS. Highly prevalent vitamin D deficiency and insufficiency in an urban cohort of HIV-infected men under care. AIDS Patient Care and STDS. 2010 Apr;24(4):223-7.
  6. Mueller NJ, Fux CA, Ledergerber B, et al. High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients. AIDS. 2010 May 15;24(8):1127-34.
  7. Mehta S, Giovannucci E, Mugusi FM, et al. Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality. PLoS One. 2010 Jan 19;5(1):e8770.
  8. Bang UC, Shakar SA, Hitz MF, et al. Deficiency of 25-hydroxyvitamin D in male HIV-positive patients: a descriptive cross-sectional study. Scandinavian Journal of Infectious Diseases. 2010 Apr;42(4):306-10.
  9. Mehta S, Hunter DJ, Mugusi FM, et al. Perinatal outcomes, including mother-to-child transmission of HIV, and child mortality and their association with maternal vitamin D status in Tanzania. Journal of Infectious Diseases. 2009 Oct 1;200(7):1022-30.
  10. Rodríguez M, Daniels B, Gunawardene S, et al. High frequency of vitamin D deficiency in ambulatory HIV-positive patients. AIDS Research and Human Retroviruses. 2009 Jan;25(1):9-14.
  11. Van Den Bout-Van Den Beukel CJ, Fievez L, Michels M, et al. Vitamin D deficiency among HIV type 1-infected individuals in the Netherlands: effects of antiretroviral therapy. AIDS Research and Human Retroviruses. 2008 Nov;24(11):1375-82.
  12. Welz T, Childs K, Ibrahim F, et al. Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AIDS 2010 Jul 31;24(12):1923-8.
  13. Gyllensten K, Josephson F, Lidman K, et al. Severe vitamin D deficiency diagnosed after introduction of antiretroviral therapy including efavirenz in a patient living at latitude 59 degrees N. AIDS 2006 Sep 11;20(14):1906-7.
  14. Ikezoe T, Bandobashi K, Yang Y, et al. HIV-1 protease inhibitor ritonavir potentiates the effect of 1,25-dihydroxyvitamin D3 to induce growth arrest and differentiation of human myeloid leukemia cells via down-regulation of CYP24. Leukemia Research. 2006 Aug;30(8):1005-11.
  15. Ellfolk M, Norlin M, Gyllensten K, et al. Regulation of human vitamin D(3) 25-hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells. Molecular Pharmacology. 2009 Jun;75(6):1392-9.
  16. Cozzolino M, Vidal M, Arcidiacono MV, et al. HIV protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS. 2003 Mar 7;17(4):513-20.
  17. Spector SA. Vitamin D earns more than a passing grade. Journal of Infectious Diseases. 2009 Oct 1;200(7):1015-7.
  18. Engel P, Fagherazzi G, Boutten A, et al. Serum 25(OH) vitamin D and risk of breast cancer: a nested case-control study from the French E3N cohort. Cancer Epidemiology, Biomarkers & Prevention. 2010 Sep;19(9):2341-50.
  19. Michaëlsson K, Baron JA, Snellman G, et al. Plasma vitamin D and mortality in older men: a community-based prospective cohort study. American Journal of Clinical Nutrition. 2010 Oct;92(4):841-8.
  20. Reddy Vanga S, Good M, Howard PA, et al. Role of vitamin D in cardiovascular health. American Journal of Cardiology. 2010 Sep 15;106(6):798-805.
  21. Fox J, Peters B, Prakash M, et al. Improvement in vitamin D deficiency following antiretroviral regimen change: results from the MONET trial. AIDS Research and Human Retroviruses. 2010;26(11): in press.
  22. Brown TT, McComsey GA. Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D. Antiviral Therapy. 2010;15(3):425-9.
  23. Anderson JL, May HT, Horne BD, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. American Journal of Cardiology. 2010 Oct 1;106(7):963-8.
  24. Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Archives of Internal Medicine. 2008 Jun 23;168(12):1340-9.


  
  • Email Email
  • Comments Comments
  • Printable Single-Page Print-Friendly
  • Glossary Glossary
  • PDF PDF

This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.
 
See Also
More on Vitamin D and HIV/AIDS

No comments have been made.
 

Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read TheBody.com's Comment Policy.)

Your Name:


Your Location:

(ex: San Francisco, CA)

Your Comment:

Characters remaining:

Tools
 

Advertisement