PMID- 24825167
OWN - NLM
STAT- MEDLINE
DCOM- 20150106
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 5
DP  - 2014
TI  - Simplification to abacavir/lamivudine + atazanavir maintains viral suppression 
      and improves bone and renal biomarkers in ASSURE, a randomized, open label, 
      non-inferiority trial.
PG  - e96187
LID - 10.1371/journal.pone.0096187 [doi]
LID - e96187
AB  - OBJECTIVE: Simplification of antiretroviral therapy in patients with suppressed 
      viremia may minimize long-term adverse effects. The study's primary objective was 
      to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV) was 
      virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir 
      (TDF/FTC+ATV/r) over 24 weeks in a population of virologically suppressed, HIV-1 
      infected patients. DESIGN: This open-label, multicenter, non-inferiority study 
      enrolled antiretroviral experienced, HIV-infected adults currently receiving a 
      regimen of TDF/FTC+ATV/r for >/= 6 months with no history of virologic failure and 
      whose HIV-1 RNA had been </= 75 copies/mL on 2 consecutive measurements including 
      screening. Patients were randomized 1 ratio 2 to continue current treatment or 
      simplify to ABC/3TC+ATV. METHODS: The primary endpoint was the proportion of 
      patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic 
      Response (TLOVR) algorithm. Secondary endpoints included alternative measures of 
      efficacy, adverse events (AEs), and fasting lipids. Exploratory endpoints 
      included inflammatory, coagulation, bone, and renal biomarkers. RESULTS: After 24 
      weeks, ABC/3TC+ATV (n = 199) was non-inferior to TDF/FTC+ATV/r (n = 97) by both 
      the primary analysis (87% in both groups) and all secondary efficacy analyses. 
      Rates of grade 2-4 AEs were similar between the two groups (40% vs 37%, 
      respectively), but an excess of hyperbilirubinemia made the rate of grade 3-4 
      laboratory abnormalities higher in the TDF/FTC+ATV/r group (30%) compared with 
      the ABC/3TC+ATV group (13%). Lipid levels were stable except for HDL cholesterol, 
      which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers 
      improved significantly between baseline and Week 24 in patients taking 
      ABC/3TC+ATV, and the difference between groups was significant at Week 24. No 
      significant changes occurred in any inflammatory or coagulation biomarker within 
      or between treatment groups. CONCLUSIONS: After 24 weeks, simplification to 
      ABC/3TC+ATV from TDF/FTC+ATV/r maintained viral suppression was well-tolerated, 
      and led to improvements in bone and renal biomarkers and HDL cholesterol. TRIAL 
      REGISTRATION: ClinicalTrials.gov NCT01102972 GlaxoSmithKline Clinical Study 
      Register #113734.
FAU - Wohl, David A
AU  - Wohl DA
AD  - AIDS Clinical Trials Unit, University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina, United States of America.
FAU - Bhatti, Laveeza
AU  - Bhatti L
AD  - AIDS Healthcare Foundation, Beverly Hills, California, United States of America.
FAU - Small, Catherine B
AU  - Small CB
AD  - New York Medical College, Valhalla, New York, United States of America.
FAU - Edelstein, Howard
AU  - Edelstein H
AD  - Alameda County Medical Center, Oakland, California, United States of America.
FAU - Zhao, Henry H
AU  - Zhao HH
AD  - GlaxoSmithKline, Research Triangle Park, North Carolina, United States of 
      America.
FAU - Margolis, David A
AU  - Margolis DA
AD  - GlaxoSmithKline, Research Triangle Park, North Carolina, United States of 
      America.
FAU - DeJesus, Edwin
AU  - DeJesus E
AD  - Orlando Immunology Center, Orlando, Florida, United States of America.
FAU - Weinberg, Winkler G
AU  - Weinberg WG
AD  - Kaiser Foundation Health Plan of Georgia, Inc, Atlanta, Georgia, United States of 
      America.
FAU - Ross, Lisa L
AU  - Ross LL
AD  - ViiV Healthcare, Research Triangle Park, North Carolina, United States of 
      America.
FAU - Shaefer, Mark S
AU  - Shaefer MS
AD  - ViiV Healthcare, Research Triangle Park, North Carolina, United States of 
      America.
LA  - eng
SI  - ClinicalTrials.gov/NCT01102972
GR  - P30 AI050410/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140513
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (Drug Combinations)
RN  - 0 (Lipids)
RN  - 0 (Oligopeptides)
RN  - 0 (Pyridines)
RN  - 0 (abacavir, lamivudine drug combination)
RN  - 2T8Q726O95 (Lamivudine)
RN  - 4MT4VIE29P (Atazanavir Sulfate)
SB  - IM
EIN - PLoS One. 2014;9(7):e103925. Dosage error in article text
MH  - Adult
MH  - Aged
MH  - Anti-HIV Agents/adverse effects/pharmacology/*therapeutic use
MH  - Antiretroviral Therapy, Highly Active/adverse effects
MH  - Atazanavir Sulfate
MH  - Biomarkers/blood
MH  - Dideoxynucleosides/adverse effects/pharmacology/*therapeutic use
MH  - Drug Combinations
MH  - Female
MH  - HIV Infections/blood/*drug therapy
MH  - Humans
MH  - Lamivudine/adverse effects/pharmacology/*therapeutic use
MH  - Lipids/blood
MH  - Male
MH  - Middle Aged
MH  - Oligopeptides/adverse effects/pharmacology/*therapeutic use
MH  - Pyridines/adverse effects/pharmacology/*therapeutic use
MH  - Treatment Outcome
MH  - Viral Load/*drug effects
MH  - Young Adult
PMC - PMC4019479
COIS- Competing Interests: The EPZ113734 study was sponsored by ViiV Healthcare 
      (www.viivhealthcare.com) which along with Dr. Wohl developed the study design 
      with input from study investigators who were contracted by ViiV Healthcare to 
      collect and assist in the analyses of the clinical data, and contracted with 
      GlaxoSmithKline to collect and analyze the clinical data. H.H.Z. and D.A.M. are 
      employed by GlaxoSmithKline. L.L.R. and M.S.S. are employed by ViiV Healthcare 
      (the makers of the fixed dose formulation of abacavir and lamivudine). All four 
      have retirement benefits that include GlaxoSmithKline stock or options. D.W. and 
      C.B.S. previously had grants from ViiV Healthcare. E.D. has received payment for 
      lectures (including Speakers Bureaus) from Gilead Sciences and Janssen as has 
      L.B. from BristolMyersSquibb, Janssen, Merck and ViiV. L.B. holds stock in Gilead 
      Sciences and has served on advisory boards for Boehringer Ingelheim, 
      BristolMyersSquibb, Genentech, and Gilead Sciences. There are no further patents, 
      products in development or marketed products to declare. This does not alter the 
      authors' adherence to all the PLOS ONE policies on sharing data and materials, as 
      detailed online in the guide for authors.
EDAT- 2014/05/16 06:00
MHDA- 2015/01/07 06:00
PMCR- 2014/05/13
CRDT- 2014/05/15 06:00
PHST- 2013/10/03 00:00 [received]
PHST- 2014/04/03 00:00 [accepted]
PHST- 2014/05/15 06:00 [entrez]
PHST- 2014/05/16 06:00 [pubmed]
PHST- 2015/01/07 06:00 [medline]
PHST- 2014/05/13 00:00 [pmc-release]
AID - PONE-D-13-41850 [pii]
AID - 10.1371/journal.pone.0096187 [doi]
PST - epublish
SO  - PLoS One. 2014 May 13;9(5):e96187. doi: 10.1371/journal.pone.0096187. eCollection 
      2014.