Effect of Antiretroviral Therapy on Bone and Renal Health in Young Adults Infected With HIV in Early Life

J Clin Endocrinol Metab. 2017 Aug 1;102(8):2896-2904. doi: 10.1210/jc.2017-00197.

Abstract

Context: HIV antiretroviral (ARV) therapy is associated with renal and bone toxicity, but little is known about the potential cumulative effects in adults exposed to ARVs from birth.

Objective: To prospectively evaluate renal and bone health in young adults with lifelong HIV and extensive ARV exposure.

Design: Cross-sectional comparison of bone mineral density (BMD) by dual-energy X-ray absorptiometry, bone turnover, and renal function in young adults infected with HIV in early life (n = 65) to matched healthy controls (n = 23) and longitudinal evaluation (mean follow-up = 4.4 years) within a subset of the HIV cohort (n = 33).

Setting: Government outpatient research clinic.

Results: Albumin/creatinine ratio, protein/creatinine ratio, anion gap, N-terminal telopeptides, and osteocalcin were significantly increased in persons with HIV compared with controls, whereas whole-body BMD and BMD z scores were lower. Within the HIV group, duration of tenofovir disoproxil fumarate (TDF) correlated with higher anion gap but did not correlate with bone parameters. Longer duration of didanosine and stavudine use correlated with lower BMD and BMD z scores. Longitudinal analyses revealed that BMD and bone metabolism significantly improved over time. No subject had an estimated glomerular filtration rate (eGFR) <60, but decline in eGFR correlated with increasing years of TDF exposure.

Conclusions: Subclinical markers of renal dysfunction were increased in HIV-infected young adults and associated with TDF exposure, whereas lower bone density was associated with didanosine and stavudine exposure. The tendency for improvement in markers of bone health over time and the availability of less toxic ARV alternatives may herald improvements in renal and bone health for perinatally infected patients in adulthood.

Trial registration: ClinicalTrials.gov NCT01656564 NCT00924365.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Absorptiometry, Photon
  • Acid-Base Equilibrium
  • Adult
  • Age of Onset
  • Albuminuria
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Bone Density*
  • Bone Diseases, Metabolic / complications
  • Bone Diseases, Metabolic / diagnostic imaging*
  • Bone Diseases, Metabolic / metabolism
  • Bone Remodeling*
  • Case-Control Studies
  • Creatinine / urine
  • Cross-Sectional Studies
  • Didanosine / therapeutic use
  • Female
  • Glomerular Filtration Rate
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • Humans
  • Kidney Function Tests
  • Longitudinal Studies
  • Male
  • Osteocalcin / metabolism
  • Prospective Studies
  • Proteinuria
  • Renal Insufficiency / complications
  • Renal Insufficiency / urine*
  • Risk Factors
  • Stavudine / therapeutic use
  • Tenofovir / therapeutic use
  • Time Factors
  • Young Adult

Substances

  • Anti-HIV Agents
  • Osteocalcin
  • Tenofovir
  • Creatinine
  • Stavudine
  • Didanosine

Associated data

  • ClinicalTrials.gov/NCT01656564
  • ClinicalTrials.gov/NCT00924365