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Immagini + Colonna sonora
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tarix | 05.10.2018 | ölçüsü | 5,91 Mb. | | #72229 |
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Immagini + Colonna sonora Dialoghi + Colonna sonora Immagini + Dialoghi
Hypothesis Hypothesis - FTC/TDF with ATV/r, RAL, or DRV/r will be equivalent in terms of virologic efficacy and tolerability over 96 weeks
Primary Endpoints* - Time to HIV-1 RNA >1000 c/mL wk 16 to before wk 24, or >200 c/mL at or after wk 24 (VF)
- Time to discontinuation of randomized component for toxicity (TF)
Pre-planned Composite Endpoint - The earlier occurrence of either VF or TF in a given participant
Equivalence shown if 97.5% CI on the pairwise difference in 96-week cumulative incidence falls entirely within -10% and +10%. Equivalence shown if 97.5% CI on the pairwise difference in 96-week cumulative incidence falls entirely within -10% and +10%. If equivalence not demonstrated, superiority shown if 97.5% CI excludes zero.
ATV/r, RAL, and DRV/r were equivalent for virologic efficacy ATV/r was less well tolerated than DRV/r or RAL - Largely due to cosmetic hyperbilirubinemia
RAL was superior to both PI/r regimens for combined tolerability and virologic efficacy - DRV/r was superior to ATV/r
VF with resistance was rare - More frequently observed with RAL
Analyses are ongoing to evaluate: - Cardiovascular, metabolic, skeletal, fat, inflammatory biomarkers, behavior, adherence, and key subgroup differences
Testo testo, testo
CKD is associated with higher risk of AMI and CVA CKD is associated with higher risk of AMI and CVA - HR for AMI: 2.41 (95% CI: 1.73-3.36)
- HR for CVA: 1.80 (95% CI: 1.44-2.24)
Phase III, randomised, open-label, multicenter, parallel-group, non-inferiority, strategic trial Phase III, randomised, open-label, multicenter, parallel-group, non-inferiority, strategic trial 78 sites, 15 countries (Austria, Belgium, Denmark, France, Germany, Great Britain, Greece, Hungary, Ireland, Italy, Netherlands, Poland, Portugal, Spain, Sweden)
Primary endpoint : Time to failure, as the first occurrence of any of the following components: Primary endpoint : Time to failure, as the first occurrence of any of the following components: Virological - V1. change of treatment before W32 because of insufficient virologic response
- HIV-1 RNA reduction < 1 log10 c/ml by W18*
- or HIV-1 RNA ≥ 400 c/ml at W24*
- V2. HIV-1 RNA ≥ 50 c/ml at W32*
- V3. HIV-1 RNA ≥ 50 c/ml at any time after W32*
- Clinical
- C1 death due to any cause
- C2. any new or recurrent AIDS defining event**
- C3. any new serious non AIDS defining event**
All patients followed-up until last patient reached W96, events recorded until end of F-U Non-inferiority margin: absolute difference of at most 9% for the failure rate of RAL vs. TDF/FTC by W96 (estimated by Kaplan-Meier methods) in the ITT analysis Major secondary endpoints: safety, changes in CD4 and HIV RNA, genotypic resistance
In this well powered, open-label randomised study In this well powered, open-label randomised study Overall twice daily RAL was well tolerated and had comparable efficacy to once daily TDF/FTC, when co-administered with once daily DRV/r, over 96 weeks in first-line ARV therapy - Primary endpoint incidence over 96 weeks was 17.4 % (RAL) vs. 13.7 % (TDF/FTC); adjusted absolute difference was 3.7%
- The upper 95% CI of 8.6% was below the pre-specified non-inferiority margin
- In a planned subgroup analysis of the outcome for patients with low CD4 (<200/mm3) RAL + DRV/r was inferior to TDF/FTC + DRV/r
Comparable safety between the 2 strategies - Similar rate of SAE, Grade 3-4 AE, AE leading to treatment modification
Treatment-emergent resistance was seen in 5/28 (RAL) vs. 0/13 (TDF/FTC) patients with available genotype at failure RAL + DRV/r represents an alternative option to TDF/FTC + DRV/r for first line therapy, particularly in patients with CD4 > 200/mm3
Anamnesi Anamnesi Algoritmi interpretativi Studio laboratoristico Studio morfometrico, QUS, DXA
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