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Lipoatrophy and Efavirenz Tied to Vitamin D Deficiency in Ontario
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First International Workshop on HIV and Aging, October 4-5, 2010, Baltimore
Mark Mascolini
Lipoatrophy more than tripled the risk of vitamin D deficiency in HIV-infected people cared for in Windsor, Ontario [1]. Current or past treatment with zidovudine (AZT) or stavudine (d4T) also raised the risk of lower vitamin D levels in this group, as did current efavirenz use and other factors. Zidovudine and stavudine are the antiretrovirals mainly implicated in development of lipoatrophy.
Vitamin D is synthesized in skin upon exposure to the sun. One mechanism associated with lower vitamin D levels in older people--decreased photosynthesis of 7-dehydrocholesterol to a vitamin D precursor, cholecalciferol--could reflect age-related lipoatrophy. Thus these investigators hypothesized that HIV-related lipoatrophy would raise the risk of vitamin D deficiency in people with HIV infection.
To test that theory, they retrospectively analyzed 217 Windsor clinic attendees who had vitamin D levels measured from 2008 through 2010, before anyone was offered supplementation. The clinic routinely measures vitamin D levels and offers supplementation to anyone with a concentration below 75 nmol/L (about 30 ng/mL). The researchers defined vitamin D deficiency as a level below 50 nmol/L (about 20 ng/mL). Windsor is the southernmost city in Canada, just south of Detroit.
The study group averaged 45.5 years in age (+/- 11.2 standard deviation [SD]), 78% were men, 24% were nonwhite, and 50% smoked. Body mass index averaged 26.4 kg/m(2) (+/- 4.7 SD). Median lowest-ever CD4 count stood at 163 (range 1 to 568), 79% of patients had a viral load below 50 copies, 63% had taken zidovudine or stavudine, 42% were taking efavirenz when they had their vitamin D level measured, and 33% were taking a protease inhibitor.
Vitamin D levels averaged 69 nmol/L (+/- 13 SD) for the group, and 33% had vitamin D deficiency.
Linear regression modeling using log-transformed vitamin D levels determined that patient- or physician-defined lipoatrophy was associated with a lower vitamin D concentration (beta = -0.063, P = 0.035), as were age under 50 (beta = -0.056, P = 0.037), nonwhite race (beta = -0.182, P < 0.001), vitamin D measurement from November through April (beta = -0.086, P = 0.001), current efavirenz use (beta = -0.061, P = 0.005), and any use of zidovudine or stavudine (beta = -0.059, P = 0.041).
Lipoatrophy more than tripled the risk of vitamin D deficiency (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7 to 7.2, P = 0.001). Other independent predictors of vitamin D deficiency were nonwhite race (OR 7.5, 95% CI 3.4 to 16.5, P < 0.001), November-through-April vitamin D measurement (OR 2.9, 95% CI 1.5 to 5.7), and current efavirenz (OR 2.0, 95% CI 1.0 to 3.8, P = 0.044).
An earlier 1077-person cross-sectional study in London correlated current efavirenz use with severe vitamin D deficiency (below 25 nmol/L) [2], and a 51-person US study found an association between starting a first-line efavirenz regimen and significant declines in vitamin D [3]. But a 312-person cross-sectional study at another London HIV clinic found no link between any antiretrovirals and low vitamin D concentrations [4].
Limitations of the study include subjectively determined lipoatrophy and the inability to distinguish between people with facial lipoatrophy versus leg or arm lipoatrophy.
The Windsor investigators believe their findings "suggest that skin synthesis of vitamin D may be affected by previous antiretroviral exposure" and that at-risk groups identified in this study may benefit from vitamin D screening. They suggested that sun exposure may not be enough to promote adequate vitamin D levels in people with HIV.
References
1. Robinson LJ, Smieja M, Quan C, et al. Association of vitamin D deficiency with lipoatrophy amongst HIV positive patients in Windsor Ontario. First International Workshop on HIV and Aging. October 4-5, 2010. Baltimore. Abstract O_06.
2. Welz T, Childs K, Ibrahim F, et al. Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AIDS. 2010;24:1923-1928.
3. Brown TT, McComsey GA. Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D. Antivir Ther. 2010;15:425-429.
4. Rashid T, Devitt E, Mandalia S, et al. No association of vitamin D levels with individual antiretroviral agents, duration of HIV-infection, alkaline phosphatase levels nor bone mineral density findings. XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract WEPDB105.
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