Vitamin D Linked to Survival in HIV

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

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

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