Head-to-head comparative trials for first line ART since 2006

Comparison of NRTI combos
Study ASSERT : ABC/3TC vs TDF/FTC
Original article : J Acquir Immune Defic Syndr. 2010 Sep;55(1):49-57 - FA Post, Antivir Ther. 2013;18(7):905-13 - GJ Moyle, Clin Infect Dis. 2010 Oct 15;51(8):963-72 HJ Stellbrink
Last update : 08/10/2014

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • No difference in estimated glomerular filtration rate between ABC/3TC + EFV and TDF/FTC + EFV
    • However, increases in markers of tubular dysfunction in the TDF/FTC arm
    • No differences in markers of glomerular dysfunction over 96 weeks
  • Significant higher virologic efficacy for TDF/FTC + EFV
    • Emergence of resistance to NNRTI and NRTI on virological failure with ABC/3TC + EFV but not with TDF/FTC + EFV
  • Incidence of grade 4 adverse events and serious adverse events was higher in the ABC/3TC arm, mainly because of drug hypersensitivity or hypersensitivity
  • Smaller increases in serum lipids with TDF/FTC
  • Greater increases in bone turnover and decreases in hip and vertebral bone mineral density with TDF/FTC + EFV compared to ABC/3TC + EFV

Design :

Primary analysis :

  • Intention to treat, exposed analysis : 2-sided significance level of 5%, with 90% power to detect a difference of 10 mL/min in eGFR (MDRD) change from baseline between arms

Baseline characteristics and patient disposition :

Adjusted mean change from baseline in eGFR by MDRD (ml/min/1.73 m2),
ITT-e population :


Repeated measures mixed model analysis

Secondary renal endpoints :

  • No differences between arms in proportion with significant declines in eGFR or with renal failure
  • Percentage change from baseline at week 48
  • Urinary retinol-binding protein/creatinine ratio : TDF/FTC = + 50% vs ABC/3TC = 0% (p < 0.0001)
  • Urinary b2-microglobulin/creatinine ratio : TDF/FTC = + 24% vs ABC/3TC = - 47% (p < 0.0001)
  • No proximal renal tubular dysfunction over 96 weeks

Changes in bone density (DXA) at week 48 :

Bone turnover markers : increased in both groups over the first 24 weeks (significantly greater with TDF/FTC), stabilizing or decreasing thereafter

Efficacy at week 48 :

Protocol-defined virologic failure (< 1 log10 c/mL reduction in HIV RNA by W4, confirmed rebound ≥ 400 c/mL after confirmed HIV RNA < 400 c/mL by W24 or confirmed HIV RNA > 400 c/mL after W24)

  • 6 on ABC/3TC + EFV
  • Emergence of resistance : 3/6
    • 2 patients with NNRTI mutations
    • 1 patient with NNRTI mutation and K65R + D67N
  • 2 on TDF/FTC + EFV = no resistance emergence

Median CD4/mm3 increase at W48 : + 150 in both groups

Safety at W48 :


 

 

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