Tenofovir clearance is reduced in HIV-positive patients with subclinical tubular impairment

AIDS. 2016 Mar 27;30(6):915-20. doi: 10.1097/QAD.0000000000000995.

Abstract

Objective: To assess if tenofovir (TFV) clearance is associated with urinary retinal-binding protein (RBP) in HIV-positive patients with normal estimated filtration rate.

Design: A cross-sectional diagnostic study.

Methods: HIV-positive patients with estimated creatinine clearance above 60 ml/min, on tenofovir disoproxil fumarate (TDF)-containing combination since at least 6 months, taking TDF at night, and without significant comorbidities (diabetes, untreated hypertension, known renal malformations, recurrent nephrolithiasis) and nephrotoxic drugs were included. TFV plasma and urinary concentrations were measured 12 h after drug intake (C12). RBP was measured through enzyme immunoassay kit on spot urines and corrected per urinary creatinine (uRBP/uCr); normality ranges were below 130 μg/g (in patients aged <50 years) and below 172 μg/g (in patients aged ≥50 years).

Results: Two hundred and eighty-nine patients were included (median age of 45.8 years, 71.6% male and 85.4% whites); patients were concomitantly treated with nonnucleoside reverse transcriptase inhibitors (155, 53.6%), protease inhibitors (118, 40.8%), or integrase inhibitors (16, 5.5%)-containing regimens. Estimated creatinine clearance was 89.4 ml/min (78.6-105.9). Urinary RBP (uRBP) and uRBP/uCr were 204.6 ng/ml (92-380) and 169.7 μg/g (85.8-318.3), respectively; abnormally high uRBP/uCr was observed in 157 patients (54.3%). A multivariate binary logistic regression confirmed that both ethnicity (P = 0.004, β 2.93, 95% confidence interval 1.41-6.10) and TFV urinary C12 less than 21 mg/ml (P = 0.006, β 2.04, 95% confidence interval 1.12-3.41) were significantly associated with abnormal uRBP/uCr.

Conclusion: HIV-positive TDF-treated patients showed a high prevalence of proximal tubular impairment: ethnicity (whites) and low urinary TFV concentrations were significantly associated with elevated uRBP. SDC VIDEO:: http://links.lww.com/QAD/A852.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics*
  • Asymptomatic Diseases
  • Cross-Sectional Studies
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Humans
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Plasma / chemistry
  • Renal Insufficiency / pathology*
  • Tenofovir / administration & dosage
  • Tenofovir / pharmacokinetics*
  • Urine / chemistry

Substances

  • Anti-HIV Agents
  • Tenofovir