Vitamin D Linked to HIV Disease Progression

SUMMARY EuroSIDA researchers found that more than 80% of HIV positive people on antiretroviral therapy (ART) had vitamin D deficiency, which was associated with higher risk of AIDS-related illness and death.

A growing body of evidence indicates that low vitamin D levels are common and can lead to detrimental health effects in people with HIV as well as the population at large.

Vitamin D may be obtained through food and is produced by the body when the skin is exposed to sunlight. Darker skinned individuals and people who live in colder climates where less skin is exposed are more prone to low levels.

As described in the April 25, 2011, advance online edition of AIDS, Jean-Paul Viard and fellow investigators with the EuroSIDA Study Group examined the association between vitamin D levels and disease progression in HIV positive people.

The study included 2000 participants in the large EuroSIDA study from Europe and Argentina who were randomly selected for vitamin D measurement using stored plasma samples. Participants were taking combination antiretroviral therapy (ART).

Levels of 25-hydroxyvitamin D, or 25(OH)D -- the precursor to the physiologically active form -- were stratified into tertiles, or thirds (< 12, 12-20, and > 20 ng/mL). The researchers analyzed factors associated with low vitamin D levels, as well as associations between vitamin D and AIDS-related events, non-AIDS events, and all-cause mortality. Participants were followed for a median of 5 years.

Results

	Among 1985 participants with vitamin D levels available:
	23.7% had 25(OH)D < 10 ng/mL, or deficient; 65.3% had levels between 10 and 30 ng/mL, or low; 11.0% had > 30 ng/mL, or normal.
	The following factors were significantly associated with greater likelihood of low vitamin D levels:
	Older age; Black race/ethnicity; Living outside southern Europe or Argentina; Blood samples obtained during winter; HIV transmission route other than male-male sex (i.e., injection drug use or heterosexual transmission).
	Conversely, participants taking HIV protease inhibitors were less likely to have low vitamin D.
	Compared to those in the lowest 25(OH)D tertile, those in the middle and highest tertiles had significantly lower risk of clinical disease progression during follow-up:
	AIDS-related events occurred in 10% of people in the lowest, 6% in the middle, and 5% in the highest tertile; adjusted incidence rate ratio 0.58 for middle tertile and 0.61 for highest tertile, or about 40% lower risk. All-cause mortality rates were 11% in the lowest, 7% in the middle, and 6% in the highest tertile; adjusted incidence rate ratios 0.68 and 0.56, respectively. Non-AIDS events occurred in 9%, 7%, and 7%, respectively, representing a slight but non-significant reduction in the middle and highest tertiles.
	There were no significant differences between people in the middle vs highest tertiles for any of these outcomes.

Based on these findings, the study authors wrote, "25(OH)D deficiency was frequent in HIV-infected persons (83% on combination ART), and was independently associated with a higher risk of mortality and AIDS events."

Studies across Europe have found vitamin D levels below 10 ng/mL in 2% to 30% of adults in the general population, they noted in their discussion. The U.S. SUN study found that about 30% of HIV positive people had levels below 20 ng/mL, compared with about 40% of participants in the NHANES general population survey. Thus "vitamin D deficiency might not be more frequent in people living with HIV than in the general population."

The EuroSIDA investigators did not see a link between use of ART overall or efavirenz (Sustiva) and lower vitamin D levels as suggested in some prior studies. The observed link between protease inhibitor use and higher 25(OH)D levels "is of unclear biological relevance," they wrote.

Having the lowest vitamin D levels remained strongly associated with AIDS-related events and all-cause mortality even after adjusting for a large number of variables including season, race/ethnicity, geographic origin, CD4 cell count, HIV viral load, anemia, and kidney function (eGFR).

"Vitamin D deficiency therefore represents a new, independent, unfavorable prognostic marker in HIV infection, but without further research this cannot translate into clinical recommendations," the authors concluded.

"These results provide strong evidence that vitamin D deficiency is an important cofactor in HIV disease progression, even in the setting of widespread, efficient combination ART," they continued. "Whether the relationship between vitamin D deficiency and events is causal must now be addressed, because of potential public health consequences."

Investigator affiliations: Centre de Diagnostic et de Thérapeutique, Hôtel-Dieu, APHP and Université Paris Descartes, Paris, France; Service d'Explorations Fonctionelles, Hopital Necker, APHP, Paris, France; Copenhagen HIV Program, Panum Institute, Copenhagen, Denmark; Department of Infection and Population Health, University College London Medical School, London, UK; Medical University, Wroclaw, Poland; Hospital JM Ramos Mejia, Buenos Aires, Argentina; Hospital Clinic i Provincial, Barcelona, Spain; Odense University Hospital, Odense, Denmark; Medizinische Poliklinik, Munich, Germany; Centre for Viral Diseases Diseases, Rigshospitalet, Copenhagen, Denmark.

5/17/11

Reference
JP Viard, JC Souberbielle, O Kirk, et al. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study. AIDS 25 (abstract). April 25, 2011 (Epub ahead of print).