Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial

Abstract

Background: The study goal was to determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C-telopeptide (CTX) in youth infected with human immunodeficiency virus (HIV) receiving and not receiving combination antiretroviral therapy (cART) containing tenofovir disoproxil fumarate (TDF).

Methods: This randomized, double-blind, placebo-controlled multicenter trial enrolled HIV-infected youth 18-25 years based on stable treatment with cART containing TDF (n = 118) or no TDF (noTDF; n = 85), and randomized within those groups to vitamin D3, 50 000 IU (n = 102) or placebo (n = 101), administered at 0, 4, and 8 weeks. Outcomes included change in TRP, PTH, BAP, and CTX from baseline to week 12 by TDF/noTDF; and VITD/placebo.

Results: At baseline, VITD and placebo groups were similar except those on TDF had lower TRP and higher PTH and CTX. At week 12, 95% in the VITD group had sufficient serum 25-hydroxy vitamin D (25-OHD; ≥20 ng/mL), increased from 48% at baseline, without change in placebo (P < .001). PTH decreased in the TDF group receiving VITD (P = .031) but not in the noTDF group receiving VITD, or either placebo group. The decrease in PTH with VITD in those on TDF occurred with insufficient and sufficient baseline 25-OHD (mean PTH change, -7.9 and -6.2 pg/mL; P = .031 and .053, respectively).

Conclusions: In youth on TDF, vitamin D3 supplementation decreased PTH, regardless of baseline 25-OHD concentration.

Clinical trials registration: NCT00490412.

Figure 1.

Participant flow diagram. Of 217 subjects screened and eligible, 207 were randomized, 203 completed a baseline visit, and 169 completed 12 weeks of study with fully evaluable data and no missed doses of vitamin D. The tenofovir disoproxil fumarate (TDF) group had 118 participants at baseline, with 59 randomized to vitamin D (52 evaluable at week 12) and 59 to placebo (48 evaluable at week 12). The noTDF group included 85 participants at baseline, with 43 randomized to vitamin D (36 evaluable at week 12) and 42 to placebo (33 evaluable at week 12). Explanations of exclusions: underlying illnesses (1 each): hypercalcemia; renal stones, recent pregnancy; psychiatric illness; hepatitis B antigen positive. Disallowed medications: trimethoprim-sulfamethoxazole, amoxicillin, penicillin, lamotrigine, mometasone nasal.

Figure 2.

Serum parathyroid hormone (PTH) concentration in all participants at baseline (A) categorized by vitamin D status (insufficient or sufficient) and combination antiretroviral therapy (tenofovir disoproxil fumarate [TDF] or noTDF); and PTH concentrations at both baseline and 12 weeks (B–E) further subdivided by randomized intervention group (vitamin D or placebo). At baseline (A) PTH was higher in participants using tenofovir (dark bars) compared with those not using tenofovir (light bars). This association of tenofovir with increased PTH was seen in those with vitamin D insufficiency (serum 25-OHD <20 ng/mL; A, left pair of bars) and in those with sufficient vitamin D status at baseline (A, right pair of bars). In the TDF group, vitamin D treatment led to a decrease in PTH from baseline to week 12, both in those with insufficient vitamin D (B) and sufficient vitamin D (C) at baseline. In the noTDF group, PTH did not change significantly in response to vitamin D treatment (D and E). Placebo treatment had no effect in any group (B–E).