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De Luca A 1,2 , Bracciale L 1 , Doino M 1 , Fabbiani M 1 , Sidella L 1 , Marzocchetti A 1 , Farina S 1 , D’Avino A 1 ,

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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De Luca A 1,2 , Bracciale L 1 , Doino M 1 , Fabbiani M 1 , Sidella L 1 , Marzocchetti A 1 , Farina S 1 , D’Avino A 1 ,

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  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. Population: baseline characteristics (n=40) Values are expressedas n (%) exceptfor*median (IQR)

  8. 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%

  9. 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)

  10. Laboratory toxicity • 14 patients with baseline grade 3 elevation of total bilirubin • New grade 3 laboratory toxicities were observed in 18 pts

  11. Cholesterol changes from baseline +21 +20 P<0.01 forallparameters at alltimepoints +18 +17 +13 Meanchange (mg/dL) +9 +4 +4 +3

  12. Triglycerides changes from baseline P=0.442 P=0.126 P=0.342

  13. 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

  14. 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

  15. Changes in ATV plasma levels (C24h or C12h) P=0.664 P=0.469 P=0.925

  16. 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

  17. 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.

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