Longitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz among individuals with HIV

AIDS. 2016 Jul 31;30(12):1935-42. doi: 10.1097/QAD.0000000000001131.

Abstract

Objective: To examine longitudinal change in vitamin D binding protein (DBP) levels during the first year after initiation of tenofovir disoproxil fumarate (TDF)/lamivudine/efavirenz and compare these findings with concurrent changes in markers of skeletal metabolism.

Design: Secondary analysis of plasma samples collected from an ongoing multicenter clinical trial.

Methods: Plasma samples collected at 0, 24, and 48 weeks after initiation of TDF + lamivudine + efavirenz from 134 adult participants enrolled in a multicenter randomized trial were analyzed. Data regarding sociodemographic and clinical characteristics were obtained as part of the parent study. Laboratory analyses included plasma DBP, intact parathyroid hormone, total 25-hydroxy vitamin D, phosphorus, the bone resorption marker collagen type 1 cross-linked C-telopeptide, and the bone formation marker total procollagen type 1 N-terminal propeptide. Repeated measures analysis of variance was used to measure changes in biomarkers over time.

Results: Our sample included 108 men and 26 women (mean age 33.6 ± 9.6 years). Median levels of DBP increased significantly from baseline to 48 weeks [154 (91.8-257.4) versus 198.3 (119.6-351.9) μg/ml, P < 0.001]. A concurrent rise in intact parathyroid hormone levels was observed over the same period [32.3 (24.4-40.9) versus 45.2 (35.1-60.4) pg/ml, P < 0.001]; however, 25-hydroxy vitamin D and phosphorus levels remained stable. Bone resorption and formation markers rapidly increased from 0 to 24 weeks, followed by a slight decline or plateau, but remained significantly elevated at 48 weeks (P < 0.001).

Conclusion: Our study provides longitudinal data supporting a potential role for DBP in bone loss associated with TDF-based therapy. Further research to elucidate the mechanistic pathways and clinical impact of these findings is warranted.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alkynes
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Benzoxazines / adverse effects
  • Benzoxazines / therapeutic use*
  • Bone Resorption / chemically induced
  • Cyclopropanes
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / pathology*
  • Humans
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Plasma / chemistry
  • Tenofovir / adverse effects
  • Tenofovir / therapeutic use*
  • Vitamin D-Binding Protein / blood*
  • Young Adult

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Vitamin D-Binding Protein
  • Lamivudine
  • Tenofovir
  • efavirenz