title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: AIDS Clinical Trials Unit, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Wohl
authors.affiliation: AIDS Healthcare Foundation, Beverly Hills, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bhatti
authors.affiliation: New York Medical College, Valhalla, NY, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Small
authors.affiliation: Alameda County Medical Center, Oakland, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Edelstein
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Research Triangle Park, NC, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Zhao
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Research Triangle Park, NC, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Margolis
authors.affiliation: Orlando Immunology Center, Orlando, FL, USA.
authors.forename: E
authors.initials: E
authors.lastname: DeJesus
authors.affiliation: Kaiser Foundation Health Plan of Georgia, Inc., Atlanta, GA, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Weinberg
authors.affiliation: ViiV Healthcare, Research Triangle Park, NC, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Ross
authors.affiliation: ViiV Healthcare, Research Triangle Park, NC, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Shaefer
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004338:Drug Combinations; D057915:Drug Substitution / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D019259:Lamivudine / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood*; D019438:Ritonavir / Q000009:adverse effects*; D016896:Treatment Outcome; D019562:Viral Load; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D015415:Biomarkers; D015224:Dideoxynucleosides; D004338:Drug Combinations; D019259:Lamivudine; D008055:Lipids; D012367:RNA, Viral; D019438:Ritonavir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir
keywords: HIV; abacavir; bone biomarkers; renal biomarker; tenofovir