Immagini + Colonna sonora

Immagini + Colonna sonora

• 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, 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

• 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

• Esame obiettivo

• Algoritmi interpretativi

• Studio laboratoristico

• Studio morfometrico, QUS, DXA