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Efavirenz and Bone Mineral Density
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Persons with HIV infection have a number of risk factors for decreased bone mineral density (BMD), related not just to effects of HIV or resulting illness but also to ART. For example, BMD decreases by as much as 5-6% after initiation of ART, and certain ARVs (eg, tenofovir, protease inhibitors) cause greater losses over time than do others. It also is becoming clearer that vitamin D deficiency or insufficiency is common among HIV-infected persons, and that efavirenz can further lower levels of vitamin D.

A recent study evaluated the effects of vitamin D + calcium supplementation on bone metabolism in ARV-naive patients who were starting efavirenz/tenofovir/emtricitabine (Atripla). ACTG 5290 randomized 165 patients to receive vitamin D 4,000 IU daily + calcium 1,000 mg daily or to placebo. Subjects had 25-OH D levels ranging from 10 ng/mL to <75 ng/mL. They were relatively well matched for baseline criteria including age (36 and 31 in the two groups, respectively) race, BMI, HIV RNA, CD4 count, and estimated daily dietary vitamin D and calcium intake.

After 48 weeks, BMD decreased 50% less in the vitamin D + calcium group than in the placebo group:

Total hip-to-waist ratio: 1.46% vs 3.19%; p < .001
Lumbar spine: 1.41% vs 2.91%; p = .085

The 25-OH D levels rose significantly in the supplemented group but did not rise in the placebo group (p < .001 for difference between groups).

Echoing the BMD results, elevations in markers of bone turnover and parathyroid were attenuated in the vitamin D + calcium group (though there were no significant differences in changes in inflammatory markers).

Clinical Bottom Line
Importantly, this small study showed that supplementation with vitamin D + calcium attenuates bone loss in patients initiating EFV/TDF/FTC. Left unanswered by this study are many questions, including whether lower dosages of vitamin D would be effective, whether patients with normal vitamin D levels would benefit, whether supplementation would be effective in persons on different ARV regimens, and how long vitamin D should be continued; these questions merit further study.

Overton ET, Chan ES, Brown TT, et al. High-dose vitamin D and calcium attenuates bone loss with ART initiation: results from ACTG A5280. In: Programs and abstracts of the 2014 Conference on Retroviruses and Opportunistic Infections; March 3-6, 2014; Boston. Abstract 133.