Darunavir/r versus Other PIs in Treatment Experienced POWER 1 and 2

Slides:

Advertisements

Similar presentations

Comparison of INSTI vs PI  FLAMINGO  GS  ACTG A5257.

Advertisements

TMC125 Safety and Tolerability: 24-week Results of the Pooled DUET-1 and -2 Trials R Haubrich, M Schechter, S Walmsley, M Peeters, M Janssens, G De Smedt.

Switch to ATV/r + RAL  HARNESS Study. ATV/r 300/100 mg qd + TDF/FTC N = 37 N = 72 ATV/r 300/100 mg qd + RAL 400 mg bid  Design Randomisation 2: 1 Open-label.

Switch to ATV/r + 3TC  SALT Study. ATV/r 300/100 mg qd + 2 NRTI (investigator-selected) N = 143 ATV/r 300/100 mg + 3TC 300 mg qd  Design Randomisation*

Comparison of INSTI vs PI  FLAMINGO  GS  ACTG A5257  WAVES.

TITAN = TMC114/r In Treatment-experienced pAtients Naïve to lopinavir

1 Atazanavir (ATV) With Ritonavir (RTV) or Saquinavir (SQV) vs Lopinavir/Ritonavir (LPV/RTV) in Patients With Multiple Virologic Failures 24-Week Results.

Combined PI and NNRTI Resistance Analysis of the Pooled DUET Trial: Towards a Regimen-Based Resistance Interpretation J. M. Schapiro, J. Vingerhoets, S.

A prospective, randomized, Phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection – ACTG 5142 Riddler S.A.,

Switch to DRV/r monotherapy  MONOI  MONET  PROTEA  DRV600.

Efficacy and Safety of Maraviroc in Treatment- Experienced (TE) Patients Infected with R5 HIV-1: 96-week Combined Analysis of the MOTIVATE 1 & 2 Studies.

Enfuvirtide for Drug-Resistant HIV Infection in North and South America Simon R. Bababeygy.

Clinical development programme for Second-Line treatment Anton Pozniak World AIDS Conference, July 2014.

DIONE – 24 week efficacy, safety, tolerability and pharmacokinetics of DRV/r QD in treatment-naïve adolescents, 12 to

SAILING Efficacy and safety of dolutegravir (DTG) in treatment- experienced INI-naïve patients DK/DLG/0041/14c September 2015.

Design of the RESIST Study Program Dr Kevin Curry Boehringer Ingelheim, Bracknell, UK.

Results From DUET-1 and DUET-2: ETR Plus DRV/RTV Associated With High Rates of Viral Suppression in Treatment-Experienced Patients This program is supported.

POWER 3 Study Confirms Safety and Efficacy of Darunavir/Ritonavir in Treatment-Experienced Patients Slideset on: Molina JM, Cohen C, Katlama C, et al.

Slideset on: Gathe J, da Silva BA, Cohen DE, et al. A once-daily lopinavir/ritonavir-based regimen is noninferior to twice-daily dosing and results in.

ACTG 5142: First-line Antiretroviral Therapy With Efavirenz Plus NRTIs Has Greater Antiretroviral Activity Than Lopinavir/Ritonavir Plus NRTIs Slideset.

First-Line Treatment of HIV Infection With Either NNRTI- or PI-Based Regimens Effective for Long-term Disease Control Slideset on: MacArthur RD, Novak.

KLEAN Study: Fosamprenavir/Ritonavir Associated With Similar Efficacy and Safety as Lopinavir/Ritonavir SGC in Treatment- Naive Patients Slideset on: Eron.

Comparison of INSTI vs PI  FLAMINGO  GS  ACTG A5257.

Tipranavir/Ritonavir Superior to Comparator PI/Ritonavir at Week 48 in Multiclass-Experienced Patients Slideset on: Hicks CB, Cahn P, Cooper DA, et al.

Phase 3 Treatment-Naïve and Treatment-Experienced

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC STaR Trial

Phase 3 Treatment Experienced

Sofosbuvir-Velpatasvir-Voxilaprevir in GT 3 and Cirrhosis POLARIS-3

Phase 3 Treatment-Naïve and Treatment-Experienced

RAL + MVC + DRV/r + TDF-FTC

EFV versus ATV + RTV, both with ABC-3TC or TDF-FTC ACTG 5202

Dolutegravir plus Rilpivirine as Maintenance Dual Therapy SWORD-1 and SWORD- 2: Design

TDF-FTC vs. ABC-3TC, each with Atazanavir + RTV or Efavirenz ACTG 5224s (Bone Effects): Study Design

undetectable (undetectable-6.25)

Lopinavir-RTV + TDF-FTC versus Maraviroc + TDF-FTC for PEP MARAVI-PEP: Study Design

Figure 1 Inclusion criteria, exclusion criteria, and criteria for virologic failure. CDC, Centers for Disease Control and Prevention; ddC, zalcitabine;

Etravirine in Treatment Experienced DUET-2 (TMC125-C216)

Switch from TDF-based to Elvitegravir-Cobicistat-TAF-FTC Study 109

Phase 3 Treatment Experienced

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

Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir in GT1b TURQUOISE-III

Lopinavir-ritonavir mg BID (n = 354)

Etravirine versus Protease Inhibitor in ARV-Experienced TMC 125-C227

Switch to Etravirine from Efavirenz due to CNS Toxicity SSAT-029 STUDY

Switch RPV-TDF-FTC from NVP-Based Regimen NEAR-Rwanda Trial

Sofosbuvir-Velpatasvir in HIV-HCV Coinfected Patients ASTRAL-5

Once Daily Etravirine versus Efavirenz in Treatment-Naive SENSE Trial

Dolutegravir versus Raltegravir in Treatment Experienced SAILING Study

Etravirine in Treatment Experienced DUET-1 (TMC125-C206)

Atazanavir + ritonavir vs. Lopinavir-ritonavir CASTLE Study

Saquinavir + RTV versus Lopinavir-RTV in Treatment-Naïve GEMINI Trial

Switching to TDF-FTC from ABC-3TC for Hyperlipidemia ROCKET II

LPV-RTV versus LPV-RTV + ZDV-3TC in Treatment-Naïve MONARK Trial

Switching the NRTI Backbone to Tenofovir DF-Emtricitabine TOTEM

Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE

Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4 PEARL-I

Phase 2b Treatment Naïve and Treatment Experienced

Phase 3 Treatment Naïve and Treatment Experienced HIV Coinfection

Switch to E/C/F/TAF + DRV

Impact of Baseline NNRTI Mutations on the Virologic Response to TMC125 in the Phase III Clinical Trials DUET-1 and DUET-2 J Vingerhoets, A Buelens, M.

Switch to DRV/r monotherapy

Switch to LPV/r monotherapy

Switch to ATV- or ATV/r-containing regimen

Switch to RAL-containing regimen

Comparison of NNRTI vs PI/r

NRTI-sparing SPARTAN PROGRESS RADAR NEAT001/ANRS 143 A VEMAN

Telaprevir in Treatment Experienced GT-1 PROVE3

A prospective, randomized, Phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection – ACTG 5142 Riddler S.A.,

NRTI-sparing SPARTAN PROGRESS RADAR NEAT001/ANRS 143 A VEMAN

Presentation transcript:

Darunavir/r versus Other PIs in Treatment Experienced POWER 1 and 2

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Study Design Study Design: POWER 1 and 2 Background: Two randomized, phase 2b trials to compare the efficacy and safety of ritonavir-boosted darunavir with other protease inhibitors in treatment- experienced HIV-infected patients with PI resistance Inclusion Criteria (n = 155) - Age ≥18 - HIV RNA >1000 copies/mL - On PI-containing regimen - History of taking >1 NRTI, and ≥1 NNRTI as part of failing regimen - At least 1 primary PI mutation at screening Treatment Arms - Darunavir 600 mg BID + Ritonavir 100 mg bid + OBR* - Investigator-selected control PI + OBR* Darunavir BID + RTV BID + OBR (n = 131) Control PI + RTV + OBR (n =124) *OBR = Optimized background regimen: ≥2 NRTIs +/- enfurvirtide Source: Clotet B, et al. Lancet. 2007;369:1169-78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 48: Virologic Response 67/110 18/120 50/110 12/120 Source: Clotet B, et al. Lancet. 2007;369:1169-78.

Baseline HIV RNA (copies/mL) Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 48: Virologic Response ( ITT-TLOVR) Baseline HIV RNA (copies/mL) Source: Clotet B, et al. Lancet. 2007;369:1169-78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 48: Virologic Response, by Primary PI Mutations at Baseline Source: Clotet B, et al. Lancet. 2007;369:1169-78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 48: Virologic Response, by DRV-Associated Mutations at Baseline Source: Clotet B, et al. Lancet. 2007;369:1169-78.

Control PI + RTV + OBR (n = 124) Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result ACTG Grade 3 or 4 Adverse Events (≥ 1% incidence regardless of causality) Data given for Number of Patients DRV + RTV + OBR (n = 131) Control PI + RTV + OBR (n = 124) Abdominal pain 3 Neutropenia 2 Diarrhea Injection site reaction (2° enfuvirtide) 1 Acute renal failure Hip arthroplasty Peripheral neuropathy Anemia Weight decreased Pneumonia Fatigue Hyperbilirubinemia Herpes zoster Source: Clotet B, et al. Lancet. 2007;369:1169-78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Conclusions Interpretation: “Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.” Source: Clotet B, et al. Lancet. 2007;369:1169-78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 24: Virologic Response, by Viral Susceptibility at Baseline Darunavir + RTV + OBR Control PIs Source: Posniak A, et al. AIDS Res Hum Retroviruses. 2008;24:1275-80.