SPIRIT STUDY Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen - - PowerPoint PPT Presentation

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

SPIRIT STUDY

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Study Design

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

Immediate Switch Arm

RPV-TDF-FTC QD

(n = 317)

Delayed Switch Arm PI/r + 2 NRTIs x 24 weeks, then RPV-TDF-FTC QD

(n = 159)

Study Design: SPIRIT STUDY

• Background: Open label, randomized phase 3b

trial evaluating switching from ritonavir-boosted PI plus 2 NRTIs to single-tablet regimen of rilpivirine-tenofovir DF-emtricitabine once daily

• Inclusion Criteria (n = 476)
• Age >18 years
• HIV RNA <50 copies/mL for >6 months
• On PI/r >6 months
• No known resistance to study drugs
• Treatment Arms
• Rilpivirine-tenofovir DF-emtricitabine
• Ritonavir-boosted PI + 2 NRTIs x 24 weeks,

then rilpivirine-tenofovir DF-emtricitabine

1x 2x

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Study Design

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

Baseline Antiretroviral Regimens Immediate Switch Arm

(n = 317)

Delayed Switch Arm

(n= 159)

NRTI at Screening TDF-FTC 80.4% 81.8% ABC-3TC 13.2% 13.2% Ritonavir-Boosted PI at Screening Atazanavir 38.5% 34.0% Lopinavir 30.6% 36.5% Darunavir 19.9% 20.8% Fosamprenavir 7.9% 7.5% Saquinavir 1.9% 1.3%

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Week 24 Virologic Response (Intent-to-Treat Analysis)

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

94 95 95 90 89 92 20 40 60 80 100 Overall ≤100,000 copies/mL >100,000 copies/mL HIV RNA <50 copies/mL (%)

Baseline HIV RNA Level RPV-FTC-TDF PI/r + 2NRTIs

297/317 143/159 155/163 83/93 125/131 48/52

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Virologic Failure (HIV RNA ≥50 copies/mL) at Weeks 24 and 48

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

0.9 2.5 5.0 1.3 2 4 6 8 24 Weeks 48 Weeks

Virologic Failure (%) Study Week Immediate switch Delayed switch

3/317 8/159 8/317 2/152

Week 24: Change in Plasma Lipids from Baseline

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

• 25
• 16
• 53
• 6
• 1

3 1

• 80
• 60
• 40
• 20

20 Total Cholesterol LDL Triglycerides HDL

Mean change from baseline (mg/dl)

RPV-FTC-TDF PI/r + 2NRTIs

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Week 48: Change in Plasma Lipids from Baseline

Source: Palella FJ, et al. AIDS. 2014;28(3):335-44.

• 24
• 16
• 64
• 2
• 24
• 14
• 80
• 4
• 100
• 80
• 60
• 40
• 20

Total Cholesterol LDL HDL Triglycerides

Mean change from baseline (mg/dl)

Immediate switch Delayed switch

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Week 48 Virologic Outcomes in Patients with Resistance Mutations*

Source: Porter DP, et al. HIV Clin Trials. 2016;17:29-37.

83 6 11 20 40 60 80 100 Virologic Suppression Virologic Failure No Data in Window

Patients (%) RPV-FTC-TDF-treated patients

*Pre-existing NRTI or NNRTI resistance mutations by baseline proviral DNA or historical RNA genotype

29/35 2/35 4/35

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Conclusions

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

Conclusion: “Switching to the STR RPV/FTC/TDF from an RTV- boosted protease inhibitor regimen in virologically suppressed, HIV-1- infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL, and triglycerides.”

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Patient-Reported Outcomes

38 17 29 9 19 28 29 25 19 21 28 23 13 46 17 34 12 50 36 31 30 27 35 32 36 17

10 20 30 40 50 60

Fatigue Fever Memory Loss Nausea Diarrhea Sadness Anxiety Skin Problems Headache Bloating Muscle pain Sex problems Weight loss

Occurrence of HIV-Related Symptoms (%)

PI/r + 2NRTIs RPV-TDF-FTC

Source: Brunetta J, et al. Patient. 2015;8:257-67.

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Conclusions

Source: Brunetta J, et al. Patient. 2015;8:257-67.

Conclusions: “These data suggest that switching to the STR RPV/FTC/TDF from a PI-based multi-pill regimen is associated with greater patient-reported treatment satisfaction and improved tolerability in HIV-1-infected, virologically suppressed individuals.”

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.