Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus Darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial

PLoS One. 2013 Aug 8;8(8):e73639. doi: 10.1371/journal.pone.0073639. eCollection 2013.

Abstract

Background: Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL) plus ritonavir-boosted Darunavir (DRV/r) in patients with suppressed viral load.

Methods: This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r) plus tenofovir/emtricitabine (TVD), who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR) at 48 weeks calculated with Cockcroft-Gault equation.

Results: 58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD). Greater than 10% improvement in eGFR was noted in 6 (25%) out of 24 with RAL+DRV/r and 3 (11%) of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354). Sensitivity analyses using three other equations for eGFR showed the same results. Urinary β2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 µg/gCr, p=0.026). Per protocol analysis showed that the HIV-RNA was <50 copies/mL at week 48 in all patients of both arms (24 in RAL+DRV and 29 in LPV/r+TVD).

Conclusions: Switching LPV/r+TVD to RAL+DRV/r did not significantly increase the proportion of patients who showed >10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary β2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed favorable viral efficacy in patients with suppressed viral load.

Trial registration: ClinicalTrials.gov NCT01294761 http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2, Umin Clinical Trials Registry UMIN000005116 http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&language=J).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Darunavir
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Emtricitabine
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • Humans
  • Kidney / drug effects
  • Kidney / physiology
  • Kidney Function Tests
  • Lopinavir / adverse effects
  • Lopinavir / therapeutic use*
  • Male
  • Middle Aged
  • Organophosphonates / adverse effects
  • Organophosphonates / therapeutic use*
  • Pyrrolidinones / adverse effects
  • Pyrrolidinones / therapeutic use*
  • Raltegravir Potassium
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Tenofovir
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Organophosphonates
  • Pyrrolidinones
  • Sulfonamides
  • Deoxycytidine
  • Lopinavir
  • Raltegravir Potassium
  • Tenofovir
  • Emtricitabine
  • Adenine
  • Darunavir

Associated data

  • ClinicalTrials.gov/NCT01294761

Grants and funding

This work was supported by a Grant-in-Aid for the research on HIV/AIDS (H22-AIDS-001) from the Ministry of Health, Labor, and Welfare of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.