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

Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Darunavir + Ritonavir QD + Raltegravir BID

(n = 401)

Darunavir + Ritonavir QD + TDF-FTC QD

(n = 404)

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 and boosted darunavir vs. combination tenofovir DF-emtricitabine and boosted darunavir.

• Inclusion Criteria (n = 805)
• Age ≥18 years
• Antiretroviral-naïve
• HIV RNA >1,000 copies/mL
• CD4 <500 cells/mm3
• No major resistance mutations
• 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

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC

NEAT001/ANRS143: Result

Week 96: Treatment Failure, by Baseline HIV RNA*

Source: Raffi F, et al. Lancet. 2014;384:1942-51.

18 7 37 14 7 27

10 20 30 40 50

Overall <100,000 copies/mL ≥100,000 copies/mL

Treatment failure (%) Baseline HIV RNA Level

Darunavir/r + Raltegravir Darunavir/r + Tenofovir DF-Emtricitabine

*Kaplan-Meier estimates of proportion of patients reaching endpoints)

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC

NEAT001/ANRS143: Result

Week 96: Treatment Failure, by Baseline CD4 Count*

Source: Raffi F, et al. Lancet. 2014;384:1942-51.

18 14 43 14 12 21

10 20 30 40 50

Overall CD4 count ≥200 CD4 count <200

Treatment Failure (%)

Baseline CD4 count (cells/mm3) Darunavir/r + Raltegravir Darunavir/r + Tenofovir DF-Emtricitabine

*Kaplan-Meier estimates of proportion of patients reaching endpoints)

9 7 60 27 9 7 30 28 20 40 60 80

CD4 <200 and HIV RNA <100,000 CD4 ≥200 and HIV RNA <100,000 CD4 <200 and HIV RNA ≥100,000 CD4 ≥200 and HIV RNA ≥100,000

Treatment failure (%) Baseline CD4 count (cells/mm3) and HIV RNA (copies/ml)

Darunavir/r + Raltegravir Darunavir/r + Tenofovir DF-Emtricitabine

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC

NEAT001/ANRS143: Result

Week 96: Treatment Failure, by HIV RNA and CD4 Count (combined effects)

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

Source: Raffi F, et al. Lancet. 2014;384:1942-51. 0.9 0.5 0.2 0.5 0.4 0.1 0.0 0.2 0.4 0.6 0.8 1.0 1.2 Total Cholesterol LDL Cholesterol HDL Cholesterol

Mean Change in Cholesterol (mmol/L) Raltegravir + Darunavir/r Darunavir/r + Tenofovir DF-Emtricitabine

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC

NEAT001/ANRS143: Result

Week 96: Change in Creatinine Clearance from Baseline

Source: Raffi F, et al. Lancet. 2014;384:1942-51. 0.8

• 4.6
• 7
• 5
• 3
• 1

1 3 5 7

Mean Change in Creatinine Clearance (mL/min) Raltegravir + Darunavir/r Darunavir/r + Tenofovir DF-Emtricitabine

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC

NEAT001/ANRS143: Substudy Result

Week 48: Changes in Spine and Hip Bone Mineral Density from Baseline

Source: Bernardadino JI, et al. Lancet HIV. 2015;2(11):e464-73.

• 1.00
• 0.73
• 2.49
• 3.30
• 5
• 4
• 3
• 2
• 1

Lumbar Spine Hip

Mean % Change in BMD Raltegravir + Darunavir/r Darunavir/r + Tenofovir DF-Emtricitabine

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC

NEAT001/ANRS143: Result

Analysis of Virologic Failures and Emerging Genotypic Resistance

Source: Raffi F, et al. Lancet. 2014;384:1942-51.

Genotype Resistance Testing in NEAT001/ANRS143 Resistance Testing and Results RAL + DRV/r

(n = 401)

DRV/r + TDF/FTC

(n = 404)

Patients who underwent genotype resistance testing at virological failure

29 13

Major resistance mutations detected

6

Reverse transcriptase

1*

Protease Integrase

5**

*K65R mutation; **N155H mutation

Darunavir/r + Raltegravir versus Darunavir/r + TDF-FTC

NEAT001/ANRS143: Conclusions

Source: Raffi F, et al. Lancet. 2014;384:1942-51.

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.”

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.