Simplification from tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted protease inhibitor to ritonavir-boosted atazanavir plus lamivudine in virologically suppressed HIV-infected adults with osteopenia: a pilot study

J Antimicrob Chemother. 2022 Jun 29;77(7):1974-1979. doi: 10.1093/jac/dkac137.

Abstract

Background: Tenofovir disoproxil fumarate, particularly when given with a ritonavir-boosted PI, reduces bone mineral density (BMD) and increases bone turnover markers (BTMs). Ritonavir-boosted atazanavir plus lamivudine is a feasible simplified option. We evaluated whether switching from a triple ritonavir-boosted PI plus tenofovir disoproxil fumarate to a two-drug regimen of lamivudine plus ritonavir-boosted atazanavir would improve BMD.

Methods: Single-arm pilot study. Virologically suppressed patients on tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted PI with low BMD, without previous resistance mutations and/or virological failure to study drugs were switched to 100/300 mg of ritonavir-boosted atazanavir plus 300 mg of lamivudine once daily. The primary endpoint was BMD change by DXA at Week 48.

Results: There were 31 patients, 4 (13%) female, and median age was 40 years. Seven participants (22.5%) had osteoporosis. At 48 weeks, mean (SD) changes in spine and hip BMD were +0.01 (0.03) (P = 0.0239) and +0.013 (0.03) g/cm2 (P = 0.0046), respectively. Mean (SD) T-score changes were +0.1 (0.23) (P = 0.0089) and +0.25 (0.76) (P = 0.0197), respectively. N-telopeptide and urine tenofovir disoproxil fumarate toxicity markers showed significant improvements. One participant withdrew from the study and two were lost to follow-up. There were no virological failures, or serious or grade 3-4 adverse events.

Conclusions: Switching from a tenofovir disoproxil fumarate plus ritonavir-boosted PI triple therapy to a lamivudine plus ritonavir-boosted atazanavir two-drug regimen in virologically suppressed HIV-infected adults with low BMD was safe, increased low BMD and reduced plasma markers of bone turnover and urine markers of tenofovir disoproxil fumarate toxicity over 48 weeks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents* / therapeutic use
  • Atazanavir Sulfate / therapeutic use
  • Bone Diseases, Metabolic* / chemically induced
  • Bone Diseases, Metabolic* / prevention & control
  • Drug Substitution*
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • HIV Protease Inhibitors* / therapeutic use
  • Humans
  • Lamivudine / therapeutic use
  • Male
  • Pilot Projects
  • Ritonavir / adverse effects
  • Ritonavir / therapeutic use
  • Tenofovir / adverse effects
  • Tenofovir / therapeutic use

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Lamivudine
  • Atazanavir Sulfate
  • Tenofovir
  • Emtricitabine
  • Ritonavir

Grants and funding