title: Serum hypophosphatemia in tenofovir disoproxil fumarate recipients is multifactorial in origin, questioning the utility of its monitoring in clinical practice.
abstract: Tenofovir disoproxil fumarate (TDF) has been anecdotally associated with isolated hypophosphatemia (HP) as well as proximal tubular toxicity and renal dysfunction in which HP has consistently been a feature. Consequently, routine phosphate measurements in TDF recipients have been recommended. We identified and compared the frequency of HP in TDF recipients with that in non-TDF recipients; assessed the reproducibility of HP; identified the incidence of renal dysfunction in hypophosphatemic patients; and evaluated associations between HP and host, HIV infection, or treatment factors. This prospective observational study measured serum phosphate, urea, and creatinine in HIV-positive individuals among the following treatment groups: TDF-containing highly active antiretroviral therapy (HAART, group A), TDF-sparing HAART (group B), HAART naive (group C), and off HAART but treatment experienced (group D). Phosphate measurements were obtained in 252 patients. Seventy-two percent of patients prescribed TDF received a phosphate measurement. The frequency of HP in groups A, B, C, and D was 31%, 22%, 10%, and 14%, respectively. Seventy-eight percent of phosphate measurements were reproducible. Kaletra (P = 0.016) administration and duration of antiretroviral therapy (P = 0.023) were independently associated with HP, but elevated creatinine and urea or use of TDF was not. The etiology of HP seems to be multifactorial and unrelated to TDF or renal dysfunction. This questions the utility of routine phosphate testing, in isolation, in TDF recipients.
authors.affiliation: Brighton and Sussex University Hospitals, National Health Service Trust, Brighton, Sussex, United Kingdom.
authors.forename: Sara Louise
authors.initials: SL
authors.lastname: Day
authors.forename: Heather A
authors.initials: HA
authors.lastname: Leake Date
authors.forename: Alan
authors.initials: A
authors.lastname: Bannister
authors.forename: Matthew
authors.initials: M
authors.lastname: Hankins
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
mesh_terms: D000225:Adenine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001774:Blood Chemical Analysis; D003404:Creatinine / Q000097:blood; D005198:Fanconi Syndrome / Q000209:etiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D017674:Hypophosphatemia / Q000209:etiology*; D061466:Lopinavir; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use*; D010710:Phosphates / Q000097:blood; D011446:Prospective Studies; D011744:Pyrimidinones / Q000009:adverse effects / Q000627:therapeutic use; D015203:Reproducibility of Results; D000068698:Tenofovir; D014508:Urea / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D010710:Phosphates; D011744:Pyrimidinones; D061466:Lopinavir; D014508:Urea; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine