ECTS2016 Poster Presentations Osteoporosis: pathophysiology and epidemiology (55 abstracts)
Longitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz therapy among HIV-infected individuals
Evelyn Hsieh 1, , Liana Fraenkel 1 , Yang Han 2 , Weibo Xia 2 , Karl Insogna 1 , Michael Yin 3 , Ting Zhu 2 , Xinqi Cheng 2 & Taisheng Li 2
1Yale School of Medicine, New Haven, Connecticut, USA; 2Peking Union Medical College Hospital, Beijing, China; 3Columbia University Medical Center, New York, New York, USA.
Tenofovir disoproxil fumarate (TDF) is a critical component of first-line antiretroviral regimens for HIV worldwide. However, TDF-containing regimens have been associated with decreased bone mineral density and increased fracture risk, which may in part be mediated through secondary elevations in parathyroid hormone (PTH). Prior cross-sectional data suggest vitamin D binding protein (DBP) levels may increase with TDF exposure leading to a functional vitamin D deficiency, which could explain the increase in PTH.
We performed a secondary analysis using plasma samples collected at 0, 24, and 48 weeks after initiation of TDF/3TC/EFV from 134 adult participants enrolled in a multi-center randomized trial. Data regarding socio-demographic characteristics, body mass index, CD4+ counts, and HIV viral load were obtained as part of the parent study. Laboratory analyses included DBP, intact PTH (iPTH), total 25-hydroxyvitamin D (25OHD), phosphorus, and markers of bone resorption and formation. Repeated measures ANOVA was used to measure change in biomarkers over time.
Our sample included 108 men and 26 women (mean age 33.6±9.6 years). Median CD4+ count increased significantly from baseline to 48 weeks [290.5(201–362) vs 424(294–555) cells/mm3, P<0.001], and median viral load decreased from 53767 (IQR: 19802–136493) to 0 (IQR:0–10) copies/ml. Median levels of DBP increased significantly from baseline to 48 weeks [154(91.8–257.4) vs 198.3(119.6–351.9) μg/ml, P<0.001]. A concurrent rise in iPTH levels was observed over the same period [32.3(24.4–40.9) vs 45.2(35.1–60.4) pg/ml, P<0.001), however 25OHD and phosphorus levels remained stable. Bone resorption and formation markers increased rapidly from 0 to 24 weeks, followed by a slight decline or plateau, but remained significantly elevated at 48 weeks (P<0.001).
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.
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