Impact of tenofovir disoproxil fumarate on bone metabolism and bone mass among perinatally HIV-infected Asian adolescents

Antivir Ther. 2017;22(6):471-479. doi: 10.3851/IMP3103. Epub 2016 Oct 27.

Abstract

Background: This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents.

Methods: This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10-18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated.

Results: Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7-17.4) years and TDF treatment duration (IQR) was 2.3 (1.4-3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6-16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 (P=0.27), and -0.3 and -0.2 (P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD <30 ng/ml; P=0.001). TDF administration was positively associated with bone resorption marker (P=0.04) and negatively associated with bone formation marker (P=0.04). With data up to 4 years, neither association between TDF use and bone mass loss (BMD: P=0.09; BMAD: P=0.22), nor variation of bone mass Z-scores by TDF treatment duration (BMD: P=0.34; BMAD: P=0.58) was demonstrated.

Conclusions: Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Antiretroviral Therapy, Highly Active
  • Biomarkers
  • Bone Density / drug effects*
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism*
  • CD4 Lymphocyte Count
  • Child
  • Cross-Sectional Studies
  • Female
  • HIV Infections / diagnosis
  • HIV Infections / drug therapy*
  • Humans
  • Kidney Function Tests
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Severity of Illness Index
  • Tenofovir / pharmacology*
  • Tenofovir / therapeutic use*

Substances

  • Biomarkers
  • Tenofovir