Limited evidence that vitamin D supplements of any benefit for patients with HIV

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There is only scant evidence that vitamin D supplementation is of benefit for patients with HIV, according to UK investigators writing in the January 28th  edition of AIDS.

The authors conducted a systematic review of studies examining the prevalence of vitamin D deficiency in patients with HIV, the effects of antiretroviral therapy on vitamin D levels, the effects of vitamin D deficiency and HIV therapy on bone metabolism and fracture risk, and the benefits of vitamin D supplements.

Both cross-sectional and longitudinal studies showed that vitamin D deficiency was widespread in HIV-positive patients. Moreover, there was evidence that starting HIV therapy, especially regimens containing efavirenz (Sustiva, also in the combination pill Atripla), was accompanied by a drop in concentrations of vitamin D.  Studies also showed that bone turnover increased in the early years of antiretroviral therapy.


bone mineral density (BMD)

The higher your bone mineral content, the denser your bones are. And the denser your bones, the stronger they are and the less likely they are to break. A bone density test uses X-rays to measure how many grams of calcium and other bone minerals are packed into a segment of bone. The bones that are most commonly tested are in the spine, hip and sometimes the forearm. 


A chemical messenger which stimulates or suppresses cell and tissue activity. Hormones control most bodily functions, from simple basic needs like hunger to complex systems like reproduction, and even the emotions and mood.

longitudinal study

A study in which information is collected on people over several weeks, months or years. People may be followed forward in time (a prospective study), or information may be collected on past events (a retrospective study).

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


Bone disease characterised by a decrease in bone mineral density and bone mass, resulting in an increased risk of fracture (a broken bone).

However, the clinical consequences of vitamin D deficiency and reduced bone turnover were unclear. Nor was there sufficient evidence to advocate widespread use of vitamin D supplements by HIV-positive patients.

It is now well established that low bone mineral density and vitamin D deficiency are both common in patients with HIV. Because of this, measuring vitamin D levels is becoming a standard component of HIV care and vitamin D supplements are being widely used.

Despite this, evidence for clinical benefit and cost effectiveness of this approach to patient management is currently lacking.

Investigators therefore reviewed the findings of recent published studies looking at the issue of bone loss and its possible causes and treatment in patients with HIV.

Vitamin D insufficiency was defined as levels between 20-30 ng/dl; deficiency as levels between 10-20 ng/dl; and severe deficiency as a level below 10 ng/dl.

Prevalence of vitamin D deficiency

Research in the public domain suggested that between 29% and 73% of HIV-infected patients had vitamin D deficiency.

However, HIV per se was not the cause.

Rather, risk factors were similar to those seen in the general population and included black or Hispanic ethnicity, low exposure to ultraviolet light, measurement in the autumn or winter, increased BMI, high blood pressure and low levels of exercise.

HIV-related factors associated with vitamin D insufficiency or deficiency included duration of infection with the virus, a CD4 cell count below 200 cells/mm3, current use of antiretroviral therapy and viral load.

The importance of vitamin D to HIV-related outcomes was unclear, but one study showed that patients with levels below 12 ng/ml at baseline were more likely to develop AIDS or die.

Vitamin D deficiency and HIV therapy

Both cross-sectional and longitudinal studies consistently showed that treatment with efavirenz resulted in reductions in vitamin D levels. There was little or no evidence that protease inhibitors, NRTIs or tenofovir (Viread, also in the combination pills Truvada and Atripla) reduced vitamin D concentrations.

However, the investigators caution that the clinical significance of the small reductions in vitamin D seen in patients taking HIV therapy has not been demonstrated.

Vitamin D deficiency, antiretroviral treatment and parathyroid hormone levels

Parathyroid hormone helps regulate calcium levels. Parathyroid disease causes osteoporosis. Elevated parathyroid levels were common in patients taking HIV therapy and were associated with therapy that included tenofovir.

Vitamin D deficiency, antiretrovirals and bone turnover

The available evidence did not show a relationship between vitamin D deficiency and increased bone turnover. However, it did suggest a relationship with antiretroviral therapy. Moreover, bone turnover may be increased in patients taking tenofovir-containing regimens as well as in individuals with secondary hyperparathyroidism.

Vitamin D deficiency, HIV therapy and bone mineral density

Longitudinal research showed a relationship between vitamin D deficiency and lower bone mineral density in the hip.

Reductions in bone mineral density of between 2% and 6% after starting HIV therapy have been consistently reported, with stabilisation after six to twelve months of treatment. Tenofovir and ritonavir-boosted protease inhibitors have been especially associated with bone loss.

The magnitude of this initial loss in bone density is on a par with that seen in the first year of the menopause. However, its clinical significance, especially in a relatively young patient population, is unclear. Furthermore, the role of vitamin D deficiency in antiretroviral-associated bone loss has yet to be defined.

Vitamin D deficiency, antiretroviral treatment and fractures

Patients with HIV are approximately 60% more likely to experience a fracture than HIV-negative individuals.

However, it was unclear if vitamin D deficiency or treatment-related side-effects were the cause. The majority of these fractures were due to trauma rather than fragility.

Vitamin D supplementation

There was some evidence that supplementation resulted in transient changes in parathyroid hormone levels. However, there was no impact on bone mineral density or markers of inflammation, or lipid levels.

Recommendations for vitamin D testing and supplementation

European HIV guidelines recommend monitoring of vitamin D levels for those with a risk of deficiency, as well as individuals with osteopenia and osteoperosis. Supplements are recommended for patients with vitamin levels below 10 ng/ml.


“With the majority of HIV-positive patients receiving combination antiretroviral therapy below 50 years of age, the benefits of a universal vitamin D deficiency ‘test and treat’ strategy in terms of fracture prevention remain to be defined, especially if vitamin D is given without daily calcium supplements,” comment the authors.

They conclude, “the overall incidence of fragility fractures, especially in younger HIV-positive patients is low and this should be taken into consideration when deciding whether to measure [vitamin D0 levels and recommend vitamin D supplementation.”


Childs K et al. Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients. AIDS 26: 253-62, 2012 (click here for the free abstract).