Nearly three quarters of HIV-positive adults in a fourcity US study had low levels of vitamin D, which is essential for healthy bones and good general health.1 Blacks and Hispanics had a higher risk of vitamin D deficiency than whites. Some risk factors for vitamin D deficiency -- like hypertension and lack of exercise -- are factors that HIV-positive people can change with their doctors' help.
Healthy vitamin D levels depend upon a good diet and enough exposure to sun, which aids formation of vitamin D in the body. Vitamin D deficiency may become more common throughout the United States and other countries, as people spend more time indoors and use sunscreen outdoors.
Low vitamin D levels pose a threat to healthy bones and may have a role in hypertension, heart disease, diabetes, and cancer. All these diseases may develop more often in people with HIV than in people without HIV. And the risk of these diseases grows as HIV-positive people live to older ages, thanks to antiretroviral therapy. Vitamin D also contributes to a healthy immune system, which is necessary to control HIV infection.
Recent smaller studies in the United States, the Netherlands, and Switzerland found high rates of vitamin D deficiency in people with HIV.2-4 SUN Study investigators planned this research to confirm that finding in a larger group of US people with HIV, to compare rates of low D levels in people with and without HIV, and to identify factors that may contribute to vitamin D deficiency in people with HIV.
After people entered SUN, health workers measured their bone mineral density and levels of 25(OH)D, a form of vitamin D that reflects vitamin acquired both from sunlight and diet. No one assessed in the vitamin D analysis took vitamin D supplements. The researchers compared vitamin D levels in this HIV-positive group and people in the general US population enrolled in an ongoing study called the National Health and Nutrition Examination Survey, or NHANES. For this comparison, the researchers used NHANES data from 2003-2004 and 2005-2006.
The SUN Study team defined vitamin D insufficiency as a 25(OH)D level below 30 ng/mL (nanograms per milliliter), and they defined vitamin D deficiency as a 25(OH)D level below 20 ng/mL. The researchers used standard statistical methods to identify factors associated with vitamin D deficiency or insufficiency, regardless of what other risk factors a person might have.
In a statistical analysis that accounted for the impact of age, race, and gender, 30% of the HIV-positive group and 39% of the general-population group had vitamin D deficiency. The rate of vitamin D insufficiency was also lower in the HIV group -- 70% versus 79% in the general-population group. In both the HIV group and the general-population group, low vitamin D levels were more common in blacks and Hispanics (compared with whites) and in people with lower exposure to sunlight. In the HIV group, a higher proportion of women than men had low D levels (80% versus 69%). But female gender was not independently associated with low vitamin D in the statistical analysis described below.
The statistical analysis to identify independent predictors of vitamin D deficiency considered the impact of (1) basic personal and behavioral factors such as age, gender, race, and exercise, (2) HIV-related factors such as CD4 count, viral load, and antiretrovirals taken, (3) environmental factors such as sunlight exposure and month of blood collection to measure vitamin D, and (4) clinical factors such as weight, bone mineral density, various diseases, and non-HIV drugs.
Figure 1. Several factors independently raised or lowered the risk of low vitamin D levels in a study of 672 HIV-positive adults in the United States. More sunlight means above the median monthly average ultraviolet light exposure. BMI means body mass index, calculated as kilograms per height in meters squared. No exercise means no exercise versus exercising 3 or more days a week.
Figure 2. Having hypertension or taking a Sustiva-containing combination nearly doubled the risk of low vitamin D levels in HIV-positive people in the United States. Poor kidney function (a glomerular filtration rate below 90 mL/min/1.73 m2), taking Viread, or taking Norvir lowered the risk of low vitamin D concentrations.
This analysis showed that blacks, Hispanics, heavier people, people with hypertension, and a few other groups had a higher risk of low vitamin D levels (Figures 1 and 2). Notably, people who did not exercise had more than a 3 times higher risk of low vitamin D than people who exercised 3 or more times a week (Figure 1).
People taking Sustiva (efavirenz) had a higher risk of low vitamin D. In contrast, people taking Viread (tenofovir) or Norvir (ritonavir) had a lower risk of low vitamin D (Figure 2). Viread is part of the combination drugs Truvada and Atripla. Norvir is used to boost other protease inhibitors, such as Prezista (darunavir) and Reyataz (atazanavir). In a separate analysis, longer time taking a Sustiva-containing combination raised the risk of low vitamin D levels.
Factors that did not affect risk of low vitamin D included age, gender, time since HIV diagnosis, initial CD4 count, lowest-ever CD4 count, having an AIDS disease, having hepatitis B or C infection, having diabetes, taking a nucleoside (such as Emtriva, Epivir, or Ziagen), and taking Viramune (nevirapine).
This study also identifies risk factors for low vitamin D in people with HIV (Figures 1 and 2). Anyone with HIV can avoid or reverse some of these risk factors, including:
Using a strong sunscreen can help prevent skin cancer by blocking ultraviolet light from the sun. However, ultraviolet light helps the body form vitamin D. A healthy balance between too much sunlight and too little sunlight is hard to define. But it's probably safe to say that people who live in northern regions (where yearly sun exposure is lower) and people who spend lots of time indoors should consider outdoor activity (including exercise) on sunny days. The National Institutes of Health notes one recommendation of "approximately 5 to 30 minutes of sun between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back without sunscreen [or] moderate use of commercial tanning beds that emit 2% to 6% ultraviolet B radiation."5 Few foods contain high levels of vitamin D.5 Fatty fish, such as salmon, tuna, and mackerel -- along with cod liver oil -- are the best sources. Smaller amounts of vitamin D can be found in beef liver, cheese, and eggs.
This study found a link between taking Sustiva and low vitamin D, while taking Viread or Norvir was linked to higher vitamin D levels. Sustiva may lead to lower vitamin D by altering vitamin D processing in body. Alcohol and some anti-epilepsy drugs may lower vitamin D levels the same way. Anti-epilepsy drugs did not affect vitamin D levels in this study, and the researchers could not assess the potential impact of alcohol. In contrast, Norvir may alter vitamin D processing in the body in a way that yields higher levels. Viread may promote higher vitamin D levels by impairing kidney function (but of course impaired kidneys are not desirable).
Whether everyone with HIV should be tested for vitamin D levels remains unknown (although the authors of this study do recommend testing). Research has not shown that people with low vitamin D levels improve their health by taking vitamin D supplements. The National Institutes of Health does say that people "with limited sun exposure need to include good sources of vitamin D in their diet or take a supplement to achieve recommended levels of intake."
A committee apointed by the Institute of Medicine recommends 400 IU of vitamin D daily as the estimated average requirement, 600 IU daily as the recommended dietary allowance, and 4000 IU daily as the upper level intake for everyone from 9 to 70 years old, including pregnant and lactating women.6 But neither this committee nor the National Institutes of Health5 offers special advice for people with HIV. The National Institutes of Health does list some groups with a high risk of low vitamin D levels:5
HIV-positive people with these risk factors for low D levels -- or the risk factors found in this study -- should talk to their doctors about whether their vitamin D level should be measured and what steps they might take to raise low levels.