HIV-positive people with very low vitamin D levels were more likely to develop AIDS and to die than people with higher vitamin D levels, according to a study published online January 25 in the journal AIDS.

Low vitamin D levels have been found in numerous studies in HIV-negative people to be associated with serious illnesses, including cardiovascular disease, cancer, diabetes and kidney failure. What’s more, a number of recent studies have found that the proportion of people with HIV who have low vitamin D levels is quite high, with fewer than a quarter in some studies having ideal levels.

There remains, however, some question about what blood level of vitamin D constitutes “deficiency.” Some studies have considered 30 nanograms per milliliter (ng/ml) of 25 hydroxy vitamin D in blood to be vitamin D deficient. Others have used 20 ng/ml. All studies, however, have considered levels below 10 ng/ml to be deficient.

Questions also remain regarding the actual health consequences of vitamin D deficiency in people living with HIV. Few studies have confirmed a link between low levels and illness or death.

To explore this link, Jean-Paul Viard, MD, from the Université Paris Descartes, Paris, and his colleagues examined vitamin D levels in the blood of 1,985 HIV-positive people enrolled in the EUROSIDA study. Viard’s team split the entire cohort of those with vitamin D samples into three groups: those with more than 30 ng/ml of vitamin D, those with between 10 and 30 ng/ml and those with less than 10 ng/ml.

As with other studies, very few people—just 11 percent—had ideal levels of vitamin D. Just over 65 percent had levels between 10 and 30 ng/ml, and nearly one quarter had extremely low vitamin D levels—less than 10 ng/ml.

Sunlight is a major source of vitamin D. Thus, Viard’s study found that blood samples taken during winter were far more likely than those taken in summer to have low vitamin D levels. Also, people who lived closer to the equator in Southern Europe were less likely to have low vitamin D levels.

Consistent with other studies, older participants and black participants were significantly more likely to have deficient vitamin D levels. Contrary to previous studies, however, people taking the antiretroviral drug efavirenz (found in Sustiva and Atripla) were no more likely to have low vitamin D levels.

Viard and his colleagues did find that low vitamin D levels were connected to illness and deaths. People with less than 10 ng/ml of vitamin D in blood were twice as likely to have AIDS as those with vitamin D levels over 30 ng/ml. They were also twice as likely to die from an AIDS-related cause and about 40 percent more likely to die of a non-AIDS-related cause.

It is this latter finding, about an increase in non-AIDS-related deaths, that Viard and his colleagues call out as significant. Non-AIDS deaths, particularly those associated with cardiovascular disease, are on the rise in people with HIV. Given the strength of the association between low vitamin D levels and cardiovascular disease in HIV-negative people, the team stated that “vitamin D deficiency therefore represents a new, independent, [unfavorable] prognostic marker in HIV infection.

“These results provide strong evidence that vitamin D deficiency is an important cofactor in HIV disease progression, even in the setting of widespread, efficient [ARV therapy],” the authors conclude. “Whether the relationship between vitamin D deficiency and events is causal must now be addressed, because of potential public health consequences.”