Switching to lopinavir/ritonavir with or without abacavir/lamivudine in lipoatrophic patients treated with zidovudine/abacavir/lamivudine

J Antimicrob Chemother. 2013 Jun;68(6):1373-81. doi: 10.1093/jac/dks540. Epub 2013 Feb 5.


Background: Discontinuation of thymidine nucleoside reverse transcriptase inhibitors (tNRTIs) is the only proven strategy for improving lipoatrophy. It is unclear whether switching to NRTI-sparing or to non-thymidine NRTI-containing therapy has differential effects on body fat recovery.

Methods: This was a 96 week, open-label, randomized study in suppressed patients with moderate/severe lipoatrophy and no prior virological failure while receiving a protease inhibitor and who had their triple NRTI regimen (zidovudine/lamivudine/abacavir) switched to lopinavir/ritonavir plus abacavir/lamivudine for a 1 month run-in period and then randomized to lopinavir/ritonavir plus abacavir/lamivudine versus lopinavir/ritonavir monotherapy. The KRETA trial is registered with ClinicalTrials.gov (number NCT00865007).

Results: Of 95 patients included, 88 were randomized to lopinavir/ritonavir plus abacavir/lamivudine (n = 44) or lopinavir/ritonavir monotherapy (n = 44). Median (IQR) baseline limb fat was 2.5 (1.6-3.7) kg in the lopinavir/ritonavir plus abacavir/lamivudine group and 2.5 (2.0-5.4) kg in the lopinavir/ritonavir monotherapy group. Six patients in the triple therapy group and 13 in the monotherapy group had discontinued study drugs by week 96. Although there were limb fat gains in each group at weeks 48/96 (+324/+358 g in lopinavir/ritonavir plus abacavir/lamivudine, P = 0.09/0.07, versus +215/+416 g in the lopinavir/ritonavir monotherapy group, P = 0.28/0.16), differences between groups were not significant [difference +109 g (95% CI -442, +660)/-57 g (95% CI -740, +625)].

Conclusions: In lipoatrophic patients treated with zidovudine/lamivudine/abacavir, switching to lopinavir/ritonavir monotherapy had no additional benefit in limb fat recovery relative to switching to lopinavir/ritonavir with abacavir/lamivudine. These data suggest that non-thymidine nucleosides such as abacavir/lamivudine are not an obstacle to limb fat recovery.

Keywords: HIV; NRTI-sparing regimen; lipoatrophy; lopinavir/ritonavir monotherapy; thymidine nucleoside analogues.

Publication types

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

MeSH terms

  • Absorptiometry, Photon
  • Adipose Tissue / pathology*
  • Adult
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Antiretroviral Therapy, Highly Active / methods*
  • Atrophy
  • Body Composition / physiology
  • Chemistry, Pharmaceutical
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Intention to Treat Analysis
  • Lamivudine / adverse effects
  • Lamivudine / therapeutic use*
  • Lipids / blood
  • Lipodystrophy / complications*
  • Lopinavir / adverse effects
  • Lopinavir / therapeutic use*
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Ritonavir / adverse effects
  • Ritonavir / therapeutic use*
  • Treatment Failure


  • Dideoxynucleosides
  • HIV Protease Inhibitors
  • Lipids
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • Lamivudine
  • Ritonavir
  • abacavir

Associated data

  • ClinicalTrials.gov/NCT00865007