NEAT001/ANRS 143 Trial Darunavir/r + Raltegravir versus Darunavir/r - PowerPoint PPT Presentation

Raltegravir plus Ritonavir-Boosted Darunavir NEAT001/ANRS 143 Trial

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Study Design Study Design: NEAT001/ANRS 143 • Background : Randomized, open-label, non- inferiority trial study to evaluate the efficacy and safety of a NtRTI-sparing regimen of raltegravir Darunavir + Ritonavir QD and boosted darunavir vs. combination tenofovir + Raltegravir BID DF-emtricitabine and boosted darunavir. (n = 401) • Inclusion Criteria (n = 805) - Age ≥18 years - Antiretroviral-naïve - HIV RNA >1,000 copies/mL Darunavir + Ritonavir QD - CD4 <500 cells/mm 3 + TDF-FTC QD - No major resistance mutations (n = 404) • Treatment Arms - Darunavir 800 mg QD + Ritonavir 100 mg QD + Raltegravir 400 mg BID - Darunavir 800 mg QD + Ritonavir 100 mg QD + TDF-FTC QD Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Result Week 96: Treatment Failure, by Baseline HIV RNA* Darunavir/r + Raltegravir Darunavir/r + Tenofovir DF-Emtricitabine 50 Treatment failure (%) 40 37 27 30 18 20 14 7 10 7 0 ≥100,000 copies/mL Overall <100,000 copies/mL Baseline HIV RNA Level *Kaplan-Meier estimates of proportion of patients reaching endpoints) Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Result Week 96: Treatment Failure, by Baseline CD4 Count* Darunavir/r + Raltegravir Darunavir/r + Tenofovir DF-Emtricitabine 50 43 Treatment Failure (%) 40 30 21 18 20 14 14 12 10 0 CD4 count ≥200 Overall CD4 count <200 Baseline CD4 count (cells/mm 3 ) *Kaplan-Meier estimates of proportion of patients reaching endpoints) Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Result Week 96: Treatment Failure, by HIV RNA and CD4 Count (combined effects) Darunavir/r + Raltegravir Darunavir/r + Tenofovir DF-Emtricitabine 80 Treatment failure (%) 60 60 40 30 28 27 20 9 9 7 7 0 CD4 ≥200 and CD4 ≥200 and CD4 <200 and CD4 <200 and HIV RNA ≥100,000 HIV RNA ≥100,000 HIV RNA <100,000 HIV RNA <100,000 Baseline CD4 count (cells/mm 3 ) and HIV RNA (copies/ml) Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Result Week 96: Change in Lipids from Baseline Raltegravir + Darunavir/r Darunavir/r + Tenofovir DF-Emtricitabine 1.2 Mean Change in Cholesterol 1.0 0.9 0.8 (mmol/L) 0.6 0.5 0.5 0.4 0.4 0.2 0.2 0.1 0.0 Total Cholesterol LDL Cholesterol HDL Cholesterol Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Result Week 96: Change in Creatinine Clearance from Baseline Raltegravir + Darunavir/r Darunavir/r + Tenofovir DF-Emtricitabine 7 Mean Change in Creatinine 5 Clearance (mL/min) 3 0.8 1 -1 -3 -5 -4.6 -7 Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Substudy Result Week 48: Changes in Spine and Hip Bone Mineral Density from Baseline Raltegravir + Darunavir/r Darunavir/r + Tenofovir DF-Emtricitabine 0 Mean % Change in BMD -1 -0.73 -1.00 -2 -2.49 -3 -3.30 -4 -5 Lumbar Spine Hip Source: Bernardadino JI, et al. Lancet HIV. 2015;2(11):e464-73.

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Result Analysis of Virologic Failures and Emerging Genotypic Resistance Genotype Resistance Testing in NEAT001/ANRS143 RAL + DRV/r DRV/r + TDF/FTC Resistance Testing and Results (n = 401) (n = 404) Patients who underwent genotype 29 13 resistance testing at virological failure Major resistance mutations detected 6 0 Reverse transcriptase 1* 0 Protease 0 0 Integrase 5** 0 *K65R mutation; **N155H mutation Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC NEAT001/ANRS143: Conclusions Interpretation : “ Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL.” Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Acknowledgment The National HIV Curriculum is an AIDS Education and Training Center (AETC) Program supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $800,000 with 0% financed with non-governmental sources. This project is led by the University of Washington’s Infectious Diseases Education and Assessment (IDEA) Program. The content in this presentation are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS, or the U.S. Government.