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Safety and efficacy of treatment simplification to Atazanavir/ritonavir plus Lamivudine in patients on two NRTIs plus Atazanavir/ritonavir with optimal virologic control: 24 weeks results from a pilot study (Atazanavir and Lamivudine Simplification Study, ATLAS).

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slide1

Safety and efficacy of treatment simplification to Atazanavir/ritonavir plus Lamivudine in patients on two NRTIs plus Atazanavir/ritonavir with optimal virologic control: 24 weeks results from a pilot study (Atazanavir and Lamivudine Simplification Study, ATLAS)

De Luca A1,2, Bracciale L1, Doino M1, Fabbiani M1,

Sidella L1, Marzocchetti A1, Farina S1, D’Avino A1,

Cauda R1, Di Giambenedetto S1

1Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy

2Infectious Diseases Unit, Siena University Hospital, Siena, Italy

introduction
Introduction
  • Long term toxicity and costs of cART highlight the need of treatment simplification strategies
  • Monotherapy with boosted PIs has been investigated with controversial results
  • Dual therapy could be a suitable option in certain patients
atazanavir ritonavir lamivudine
Atazanavir/ritonavir + lamivudine
  • Tolerability:
    • ATV is a PI with a low metabolic impact;
    • 3TC generally very well tolerated.
  • Once daily administration
  • Relatively limited pill burden
  • Relatively limited costs
atlas
ATLAS
  • Pilot study (40 patients)
    • Prospective single-arm, single center, 48 weeks
    • Safety and tolerability
    • Max allowed failure rate (confirmed VL>50 cp/mL): 12.5%
    • Enrolment June 2009 – May 2010
    • Clinicaltrials.gov NCT00885482
  • Inclusion criteria:
    • Patients on ATV/rit + 2 NRTIs from at least 3 months
    • HIV-RNA <50 copies/mL from at least 3 months
    • CD4 >200 cells/µL from at least 6 months
atlas5
ATLAS
  • Exclusion criteria:
    • Previous virological failure of 3TC or PI-containing regimens or exposure to mono-dual NRTI
    • Virological failure with other regimens but a GRT with any RAM to 3TC or ATV
    • Proton pump inhibitors co-administration
    • HBsAg positive
    • Pregnancy
atlas study procedures
ATLAS: study procedures
  • At baseline simplification to ATV/rit 300/100 mg OD + 3TC 300 mg OD
  • Follow up visits at 4, 12, 24, 36 and 48 weeks
  • At each visit: chemistry, CD4 and HIV-RNA, TDM, self reported adherence (VAS)
  • At baseline and at 48 weeks: Quality of Life, self-reported symptoms, Neurocognitive assessment, Bone density (DXA), Fat distribution (DXA, Liposound), carotid IMT and endothelial function (brachial FMD)
population baseline characteristics n 40
Population: baseline characteristics (n=40)

Values are expressedas n (%) exceptfor*median (IQR)

results of 24 weeks interim analysis
Results of 24 weeks interim analysis
  • 40/40 patients completed Week 4, 38/40 Week 12, 36/40 week 24
  • All patients maintained an HIV-RNA<50copies/mL, without viremic blips
  • No significant modifications of CD4 cells count

P=0.458

P=0.402

P=0.277

Proportionofpatientswith

HIV-RNA<50copies/mL

Changes in CD4 cellscount

100%

100%

100%

100%

severe clinical adverse events
Severe clinical adverse events

A total of 5 severe adverse events were observed in 5 patients :

  • 2 renal colic
  • 1 hypertensive crisis
  • 1 brain hemorrhage
  • 1 pregnancy (the only dropped patient)
laboratory toxicity
Laboratory toxicity
  • 14 patients with baseline grade 3 elevation of total bilirubin
  • New grade 3 laboratory toxicities were observed in 18 pts
cholesterol changes from baseline
Cholesterol changes from baseline

+21

+20

P<0.01 forallparameters at alltimepoints

+18

+17

+13

Meanchange (mg/dL)

+9

+4

+4

+3

renal function change from baseline
Renal function change from baseline

+6

P=0.097

+6

P<0.001

+4

P=0.017

Meanchange (mg/dl)

Meanchange (mL/min/1.73m2)

-0.04

P=0.020

-0.06

P=0.012

-0.08

P<0.001

slide14

Bilirubin change from baseline

+0.3

P=0.07

+0.3

P=0.04

Meanchange (mg/dL)

+0.1

P=0.7

+0.1

P=0.5

+0.1

P=0.6

+0

P=0.8

conclusions
Conclusions
  • Simplification regimen with ATV/rit+3TC maintained virological suppression through 24 weeks
  • 2 severe adverse events possibly related to drugs (renal colic); no severe laboratory adverse event; bilirubin increased temporarily.
  • TC, HDL and LDL increased (a lipid-lowering effect of TDF was recently suggested)*; TC/HDL and HDL/LDL ratios were unchanged.
  • Renal function improved significantly (probably due to TDF discontinuation)

*Tungsiripat M. AIDS. 2010 Jul 17;24:1781-4

conclusions17
Conclusions
  • 48 weeks efficacy and safety results are necessary to confirm preliminary safety and efficacy of simplification to ATV/r+3TC
  • Results will form the basis for definitive testing of this strategy in a randomized controlled trial.