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Efavirenz Linked to Severe Vitamin D Deficit in Diverse London Clinic
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5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
Almost everyone tested in a diverse London HIV clinic had suboptimal vitamin D levels, and one third had severe vitamin D deficiency [1]. Among people taking antiretrovirals, current efavirenz therapy independently doubled the risk of severe deficiency. People taking tenofovir had significantly higher alkaline phosphatase readings than people not taking tenofovir.
Because several studies of people with HIV found high rates of vitamin D deficiency, clinicians at King's College Hospital London conducted a cross-sectional study of 1077 HIV-infected outpatients between June and December 2008, looking for low levels of vitamin D and high levels of alkaline phosphatase. Vitamin D, found in fish liver oils, egg yolks, and fortified dairy products, is essential for healthy bones; deficiency can cause rickets in children and osteomalacia (bone demineralization) in adults. Alkaline phosphatase may be elevated in some bone and liver diseases.
Blacks made up a majority of the London study group (60.5%), and 40.7% were female. Median age stood at 41 years (interquartile range [IQR] 36 to 47) and median CD4 count at 456 (IQR 328 to 616). Just over half of the study group (55%) had a nadir (lowest-ever) CD4 count under 200. While 12.4% had never taken antiretrovirals, 78.5% were taking a combination regimen at the time of the study, including 24.2% taking a protease inhibitor and 53.8% taking a nonnucleoside. One third of study participants were tested from October through December, when vitamin D levels drop because of diminished sunlight.
While 91.3% of the study group had a 25(OH)D level below 30 micrograms/L (suboptimal), 73.5% were below 20 micrograms/L (deficient), and 34.8% were below 10 micrograms/L (severely deficient).
Multivariate analysis determined that black (versus nonblack) race more than tripled the risk of severe vitamin D deficiency (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.5 to 4.7, P < 0.001). Measuring vitamin D during winter (versus summer) doubled the risk of severe deficiency (OR 2.2, 95% CI 1.6 to 2.9, P < 0.001), and a CD4 nadir below 200 raised the risk 40% (OR 1.4, 95% CI 1.03 to 1.8, P = 0.03). Gender, current CD4 count, kidney function (by estimated glomerular filtration rate), and serum albumin did not significantly affect the risk of severe deficiency in this analysis.
Among 845 people taking antiretrovirals, the investigators isolated four factors that independently predicted severe vitamin D deficiency: Black race more than doubled the risk (OR 2.6, 95% CI 1.8 to 3.7, P < 0.001). Measuring vitamin D in winter doubled the risk (OR 2.1, 95% CI 1.6 to 2.9, P < 0.001). Nadir CD4 count below 200 raised the risk 40% (OR 1.4, 95% CI 1.0 to 1.9, P < 0.05). And current efavirenz nearly doubled the risk (OR 1.9, 95% CI 1.3 to 2.7, P < 0.001).
Severe vitamin D deficiency affected 59.5% of blacks with a CD4 nadir below 200 who were tested during winter and taking efavirenz versus 51.4% in that subgroup not taking efavirenz. Among whites with a CD4 nadir above 200 and tested during summer, 19.5% taking efavirenz versus 11.8% not taking efavirenz had severe vitamin D deficiency.
Taking a PI, nevirapine, abacavir, tenofovir, or nucleosides had no impact on deficiency risk. However, people taking tenofovir had higher alkaline phosphatase levels than people not taking tenofovir at every vitamin D level (93, IQR 75 to 115, versus 79, IQR 64 to 97, P < 0.0001). People taking efavirenz also had significantly higher alkaline phosphatase readings than people not taking efavirenz (89, IQR 70 to 113 versus 82, IQR 68 to 103, P = 0.002). But this difference became nonsignificant when the analysis excluded people taking tenofovir with efavirenz (80 versus 70, P = 0.07).
This appears to be the first study linking efavirenz to vitamin D deficiency. The King's College researchers suggested efavirenz may alter vitamin D levels by inducing CYP24 enzymes, which promote breakdown of 25(OH)D and active vitamin D--1.25(OH)D--to inactive metabolites.
The investigators called for further study to elucidate potential mechanisms and clinical implications of these correlations between antiretroviral therapy, vitamin D, and alkaline phosphatase.
Reference
1., Welz T, Childs K, Ibrahim F, Poulton M, Post F. Efavirenz use is associated with severe Vitamin D deficiency in a large, ethnically diverse urban UK HIV cohort. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract TUPEB186.
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