Vitamin D deficiency, supplementation and tenofovir

8 June 2009. Related: Conference reports, BHIVA 15th Liverpool 2009.

Simon Collins, HIV i-Base

T Welz and colleague from Kings College Hospital presented results from a cross-sectional study of serum 25(OH)D levels in over 1000 HIV-positive adults. Median age was 40 years (IQR 35, 46), 60% men, 35% white, 58% black, CD4 452 cells/mm3 (IQR 324, 613). [1]

Just over 90% patients were defined as sub-optimal (<30 lg/L), 73% as defificient (<20 lg/L), 34% as severely defificient (<10 lg/L) and 6% with undetectable levels. Although median serum 25(OH)D was slightly higher in the summer than winter (14.2 versus 11.2 lg/L; p<0.001), this did not significantly improve the proportion of patients with less deficiency.

Factors associated with lower serum 25(OH)D were black race (p<0.001), low CD4 nadir (P<0.002) and efavirenz use (p<0.004). Tenofovir use was associated with a higher level (p=0.001). However, patients with low 25(OH)D on tenofovir were twice as likely to have an elevated ALP than those on abacavir (OR=2.4 [CI 1.5, 3.9]; and four times as likely compared to other NRTIs (OR=4.6 [CI 1.6, 13.3].

The presentation concluded that their results supported routine testing as calcium and ALP did not detect low 25(OH)D levels. Testing is inexpensive (~£20) and vitamin D supplementation is inexpensive, even when higher doses are needed.

The benefits of vitamin D and calcium supplements were reported by Childs and colleagues from Kings College London, in 32 HIV-positive men with suboptimal levels of 25(OH)D (<30 ng/mL). Daily supplement vitamin D3 (VD3) were prescribed dosed by baseline levels: 2800 IU [25(OH)D < 10]; 1800 IU [25(OH)D = 10–20]; 800 IU [25(OH)D = 20–30], all with additional 1g calcium citrate daily.

Follow-up tests were performed on 20 subjects: 16 on tenofovir-containing HAART; 4 on non-tenofovir-containing HAART. There was a strong association between suboptimal 25(OH)D levels and parathyroid abnormalities. Among the 32 subjects with suboptimal 25(OH)D, mean PTH was 80 ± 32 pg/mL in those on tenofovir and 56 ± 19 pg/mL in those on non-tenofovir HAART (p=0.02). Among subjects with suboptimal 25(OH)D, 37% (10/27) on tenofovir had PTH >ULN, indicating secondary hyperparathyroidism (SHPT), while none of the 10 subjects with low vitamin D on non- tenofovir HAART had SHPT (p=0.03).

VD3 supplementation increased 25(OH)D by 9.8 ± 5.6 ng/mL (P < 0.001) and PTH fell 18.9 ± 31.7 pg/mL (p=0.002). Parathyroid hormone (PTH) rose 4.4 pg/mL among subjects in the bottom third of baseline PTH values. In contrast, it fell 5.3 pg/mL among subjects in the middle third, and fell 44.7 pg/mL among subjects in the top third (p=0.001, ANOVA). All subjects in the upper third were on tenofovir and all experienced a PTH decrease.

The researchers concluded that VD3/calcium supplements increased serum 25(OH)D and decreased PTH and are a safe and effective treatment for HAART-associated hyperparathyroidism.

References:

1. Welz T et al. Risk factors for vitamin D defificiency in an ethnically diverse urban HIV cohort: Which antiretrovirals are implicated? 15th Annual Conference of the British HIV Association (BHIVA), 1-3 April 2009, Liverpool. Oral abstract O6.
2. Childs K et al. Vitamin D and calcium supplements reverse the secondary hyperparathyroidism that commonly occurs in HIV patients on TDF-containing HAART. 15th Annual Conference of the British HIV Association (BHIVA), 1-3 April 2009, Liverpool. Poster abstract P89.