The ASSURE study: HIV-1 suppression is maintained with bone and renal biomarker improvement 48 weeks after ritonavir discontinuation and randomized switch to abacavir/lamivudine + atazanavir

HIV Med. 2016 Feb;17(2):106-17. doi: 10.1111/hiv.12281. Epub 2015 Jul 14.


Objectives: HIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy-experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long-term adverse events (AEs). This open-label, multicentre, noninferiority study enrolled HIV-1-infected, treatment-experienced adults with confirmed HIV-1 RNA ≤ 75 HIV-1 RNA copies/mL currently receiving tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC + ATV/r) for ≥ 6 months with no reported history of virological failure.

Methods: Participants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Endpoints included the proportion of participants with HIV-1 RNA < 50 copies/mL by time to loss of virological response (TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers.

Results: After 48 weeks, 76% (152 of 199) of ABC/3TC + ATV-treated and 79% (77 of 97) of TDF/FTC + ATV/r-treated participants had HIV-1 RNA < 50 copies/mL (TLOVR; P = 0.564). Other efficacy analyses yielded similar results. Rates of new grade 2-4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment-emergent grade 3-4 laboratory abnormalities higher with TDF/FTC + ATV/r (36%) compared with ABC/3TC + ATV (19%). Most fasting lipid levels remained stable over time; high-density lipoprotein (HDL) cholesterol increased modestly in ABC/3TC + ATV-treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC + ATV and were stable in participants taking TDF/FTC + ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.

Conclusions: The ABC/3TC + ATV treatment-switch group had similar viral suppression rates up to 48 weeks to the TDF/FTC + ATV/r comparator group, with lower rates of moderate- to high-grade hyperbilirubinaemia and improvements in bone and renal biomarkers.

Keywords: HIV; abacavir; bone biomarkers; renal biomarker; tenofovir.

Publication types

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

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Atazanavir Sulfate / therapeutic use*
  • Biomarkers / blood
  • Bone Density / drug effects*
  • CD4 Lymphocyte Count
  • Dideoxynucleosides / therapeutic use*
  • Drug Combinations
  • Drug Substitution / methods
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology
  • Humans
  • Kidney / drug effects*
  • Lamivudine / therapeutic use*
  • Lipids / blood*
  • Male
  • Middle Aged
  • RNA, Viral / blood*
  • Ritonavir / adverse effects*
  • Treatment Outcome
  • Viral Load


  • Anti-HIV Agents
  • Biomarkers
  • Dideoxynucleosides
  • Drug Combinations
  • Lipids
  • RNA, Viral
  • abacavir, lamivudine drug combination
  • Lamivudine
  • Atazanavir Sulfate
  • Ritonavir