Low vitamin D levels were associated with poorer reconstitution of the immune system after starting antiretroviral (ARV) therapy in people with HIV, as well as with thickening of the carotid artery—an important predictor of cardiovascular disease (CVD). These results, published April 26 online in the journal Antiviral Therapy, are the first to confirm an association between low vitamin D levels and higher CVD risk in people with HIV.

Vitamin D has a profound influence on heart health and the immune system. Past studies have shown that inadequate levels can diminish blood vessels’ ability to function and can lead to increases in heart attacks and strokes in HIV-negative individuals. Low vitamin D levels have also been linked to higher levels of immune and blood vessel inflammation as well as poorer function of immune system cells.

Potent combination ARV therapy has resulted in dramatically improved health for HIV-positive people and cut the HIV-related death rate substantially. Given that people with HIV are living longer and are much less likely to experience diseases tied to impaired immune function, other health risks have moved to the fore of AIDS research. Given vitamin D’s known impact on both CVD risk and immune function in HIV-negative people, researchers have begun to study the connection in people with HIV.

While we know now that vitamin D levels are often lower in people with HIV, and that there is preliminary evidence of low vitamin D levels affecting immune function, no study has yet examined the connection between vitamin D and heart health among HIV-positive people. To explore this connection, Allison Ross, MD, from Emory University in Atlanta, and her colleagues tested vitamin D levels, immune function and heart health in a group of about 149 HIV-positive people enrolled in the Case Western Reserve University’s HIV clinic in Cleveland, and a matched group of 34 HIV-negative people.

Both groups were similar in most respects, though there were more males, African Americans and far more smokers in the HIV-positive group. The season of the year at the time of the test for vitamin D levels—sunlight is needed to generate the vitamin in the body, so different seasons can significantly affect levels—also differed between the two groups. All of the HIV-positive participants were on ARV therapy, and the average current CD4 was 572. The lowest ever average CD4 count recorded for the HIV-positive group was 169.

In the first analysis, it became clear that vitamin D levels were significantly lower in the HIV-positive group, even when controlling for known factors that can lower those levels. What’s more, when Ross and her colleagues compared the degree of immune restoration—which involved subtracting a person’s lowest ever CD4 count from their current CD4 count—they found that people with the poorest level of immune restoration were the most likely to have the lowest level of vitamin D.

Another analysis looked for an association between vitamin D levels and the degree of inflammation. When Ross’s team adjusted for known vitamin D risk factors, they found no significant association between low vitamin D levels and higher levels of inflammation.

Where they did find significance, however, was between low vitamin D levels and thickening of the carotid artery, the main artery of the neck supplying blood to the brain. In fact, those with the lowest vitamin D levels were more than 10 times as likely to have thickening of the artery. This is the first time this has been uncovered, and it has significant implications for CVD risk.

Though the authors acknowledge that the study is small, and that it doesn’t say that low vitamin D actually causes these differences, they are calling for further research. Not only would such research confirm the link between vitamin D and CVD risk, but it would also determine whether people starting ARVs would see better immune recovery if they took a vitamin D supplement.

The researchers conclude: “A randomized placebo-controlled interventional trial is crucial to determine what effect vitamin D may have on surrogate markers of CVD, as well as on immune function and reconstitution, and to determine what vitamin D level is optimal in HIV-positive patients.”