title: Early changes in parathyroid hormone concentrations in HIV-infected patients initiating antiretroviral therapy with tenofovir.
abstract: Initiation of combined antiretroviral therapy (cART) is associated with bone loss, which may be more intense with regimens including tenofovir. The underlying mechanisms are not well understood. Cross-sectional data have linked tenofovir with higher parathyroid hormone (PTH) concentrations in patients with vitamin D deficiency. We performed a longitudinal study with a 48-week follow-up to evaluate sequential changes in PTH and 25-hydroxyvitamin D [25(OH)D] levels in patients starting cART with either tenofovir/emtricitabine or abacavir/lamivudine. Fifty-seven patients were included, 31 initiating tenofovir/emtricitabine and 26 initiating abacavir/lamivudine. Median PTH levels turned out to be significantly higher among tenofovir/emtricitabine users at week 4 (p=0.01), week 24 (p=0.008), and week 36 (p=0.02), and were above the upper limits of normal values (ULN) at weeks 24, 36, and 48 only in patients receiving tenofovir/emtricitabine. 25(OH)D, serum and urine calcium and phosphate, and renal-tubular maximum reabsorption of phosphate to the glomerular filtration rate (TmP/GFR) levels did not differ between the two treatment arms over the study period. Among tenofovir/emtricitabine users, median (interquartile range) PTH concentrations were significantly higher in patients with suboptimal 25(OH)D levels (<30 μg/liter) at week 24 [63 (57.8-82.4) ng/liter vs. 54.3 (34.4-63.067.5) ng/liter, p=0.05] and week 48 [67.5 (59.6-86.0) ng/liter vs. 41.9 (37.3-68.8) ng/liter, p=0.03]. A multivariable logistic regression model showed that tenofovir/emtricitabine use was an independent predictor of high PTH levels (≥53 ng/liter). Starting cART with tenofovir regimens is associated with an elevation in PTH plasma concentrations soon after introducing the drug. Suboptimal baseline 25(OH)D levels increase the risk of developing secondary hyperparathyroidism among tenofovir users.
authors.affiliation: Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain. marmasia@ya.com
authors.forename: Mar
authors.initials: M
authors.lastname: Masiá
authors.forename: Sergio
authors.initials: S
authors.lastname: Padilla
authors.forename: Catalina
authors.initials: C
authors.lastname: Robledano
authors.forename: Natividad
authors.initials: N
authors.lastname: López
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Ramos
authors.forename: Felix
authors.initials: F
authors.lastname: Gutiérrez
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015519:Bone Density / Q000187:drug effects*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000008:administration & dosage; D000068679:Emtricitabine; D005260:Female; D005500:Follow-Up Studies; D006679:HIV Seropositivity / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008137:Longitudinal Studies; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D010281:Parathyroid Hormone / Q000097:blood*; D000068698:Tenofovir; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood*; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D010281:Parathyroid Hormone; D000068698:Tenofovir; D014807:Vitamin D; D000099227:Abacavir; C104450:25-hydroxyvitamin D