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

Slides:



Advertisements
Similar presentations
M ANAGING ARV REGIMEN FAILURE IN THE HIV INFECTED CHILD Dr L Keet Centre of Excellence HIV Directorate.
Advertisements

Switch to EVG/c/FTC/TDF  STRATEGY-PI Study  STRATEGY-NNRTI Study.
Initiating Antiretroviral Therapy in Treatment-Naive Patients Charles B. Hicks, MD Associate Professor of Medicine, Division of Infectious Diseases and.
Comparison of INSTI vs PI  FLAMINGO  GS  ACTG A5257.
Salvage Antiretroviral Therapy Guiding Principles, Strategies and the Role of Resistance Testing.
Comparison of PI vs PI  ATV vs ATV/r BMS 089  LPV/r mono vs LPV/r + ZDV/3TC MONARK  LPV/r QD vs BID M M A5073  LPV/r + 3TC vs LPV/r + 2.
Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir in GT1 or GT4 and HIV Coinfection ION-4 Phase 3 Treatment Naïve and Treatment Experienced.
Switch to ATV/r-containing regimen  ATAZIP. Mallolas J, JAIDS 2009;51:29-36 ATAZIP ATAZIP Study: Switch LPV/r to ATV/r  Design  Endpoints –Primary:
1 Atazanavir (ATV) With Ritonavir (RTV) or Saquinavir (SQV) vs Lopinavir/Ritonavir (LPV/RTV) in Patients With Multiple Virologic Failures 24-Week Results.
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.
Switch to LPV/r monotherapy  Pilot LPV/r  M  LPV/r Mono  KalMo  OK  OK04  KALESOLO  MOST  HIV-NAT 077.
Comparison of NNRTI vs PI/r  EFV vs LPV/r vs EFV + LPV/r –A5142 –Mexican Study  NVP vs ATV/r –ARTEN  EFV vs ATV/r –A5202.
Switch to LPV/r monotherapy  Pilot LPV/r  M  LPV/r Mono  KalMo  OK  OK04  KALESOLO  MOST  HIV-NAT 077.
Maintenance therapy with Trizivir® after 6 months induction with Trizivir® plus either efavirenz or lopinavir/r in naïve patients. Trizefal study J. Mallolas*
Switch to LPV/r monotherapy  Pilot LPV/r  M  LPV/r Mono  KalMo  OK  OK04  KALESOLO  MOST  HIV-NAT 077.
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
Comparison of NNRTI vs NNRTI  ENCORE  EFV vs RPV –ECHO-THRIVE –STAR  EFV vs ETR –SENSE.
Superior Outcome for Tenofovir DF (TDF), Emtricitabine (FTC) and Efavirenz (EFV) Compared to Fixed Dose Zidovudine/Lamivudine (CBV) and EFV in Antiretroviral.
Long-Term Comparison of Nevirapine Versus Efavirenz When Combined with Other Antiretroviral Drugs in HIV-1 Positive Antiretroviral-Naïve Persons- The NNRTI.
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.
Weekly Alendronate Safe and Effective at Increasing Bone Mineral Density in HIV-Infected Persons on Antiretroviral Therapy Slideset on: McComsey GA, Kendall.
Comparison of NNRTI vs NNRTI  ENCORE  EFV vs RPV –ECHO-THRIVE –STAR  EFV vs ETR –SENSE.
HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Slideset on: Hecht FM, Wang L, Collier A, et al. A.
Neurologic Effects Associated With Efavirenz Generally Mild, Transient Slideset on: Clifford DB, Evans S, Yang Y, et al. Impact of efavirenz on neuropsychological.
Efavirenz Use Not Associated With Depressive Episodes, According to Analysis of Randomized Clinical Trial Outcomes Slideset on: Journot V, Chene G, De.
Previous SVR With Interferon-Based Therapy for HCV Lowers Risk of Hepatotoxicity in HIV/HCV-Coinfected Individuals on Antiretroviral Therapy Slideset on:
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.
Slideset on: Emery S, Neuhaus JA, Phillips AN, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving.
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.
Tipranavir/Ritonavir Superior to Comparator PI/Ritonavir at Week 48 in Multiclass-Experienced Patients Slideset on: Hicks CB, Cahn P, Cooper DA, et al.
Adefovir Suppresses HBV DNA Levels in Lamivudine-Resistant HIV/HBV Patients Slideset on: Benhamou Y, Thibault V, Vig P, et al. Safety and efficacy of adefovir.
Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC STaR Trial
Comparison of PI vs PI ATV vs ATV/r BMS 089
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
Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen SPIRIT STUDY
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
Once Daily Etravirine versus Efavirenz in Treatment-Naive SENSE Trial
Dolutegravir versus Raltegravir in Treatment Experienced SAILING Study
Atazanavir + ritonavir vs. Lopinavir-ritonavir CASTLE Study
Darunavir/r versus Other PIs in Treatment Experienced POWER 1 and 2
Saquinavir + RTV versus Lopinavir-RTV in Treatment-Naïve GEMINI Trial
LPV-RTV versus LPV-RTV + ZDV-3TC in Treatment-Naïve MONARK Trial
Phase 3 Treatment Naïve and Treatment Experienced HIV Coinfection
Long-Term Clinical and Immunologic Outcomes Are Similar in HIV-Infected Persons Randomized to NNRTI versus PI versus NNRTI+PI-based Antiretroviral Regimens.
Switch to DRV/r monotherapy
Switch to LPV/r monotherapy
Comparison of NNRTI vs PI/r
Comparison of PI vs PI ATV vs ATV/r BMS 089
Comparison of INSTI vs EFV
Switch to LPV/r monotherapy
Comparison of NNRTI vs NNRTI
Comparison of NNRTI vs PI/r
Comparison of PI vs PI ATV vs ATV/r BMS 089
Comparison of NNRTI vs NNRTI
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 LPV/r monotherapy
Comparison of NRTI combinations
Comparison of NRTI combinations
ARV-trial.com Switch to FTC + ddI + EFV ALIZE 1.
Comparison of NNRTI vs NNRTI
Presentation transcript:

ACTG 5142: First-line Antiretroviral Therapy With Efavirenz Plus NRTIs Has Greater Antiretroviral Activity Than Lopinavir/Ritonavir Plus NRTIs Slideset on: Riddler SA, Haubrich R, DiRienzo AG, et al. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008;358: This program is supported by educational grants from Jointly sponsored by Postgraduate Institute for Medicine and Clinical Care Options, LLC

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Background  Combination of 2 NRTIs plus either EFV or LPV/RTV included among “preferred” regimens for first-line ART in current practice guidelines [1,2] –No previous adequately powered, randomized clinical trials comparing efficacy of EFV- and LPV/RTV-based regimens  Some NRTIs associated with lipoatrophy and other toxicities –Possibly avoided by combining LPV/RTV plus efavirenz [3]  Present study compared safety and efficacy of 3 first-line treatment regimens in antiretroviral-naive participants [4] –EFV plus 2 NRTIs –LPV/RTV plus 2 NRTIs –LVP/RTV plus EFV 1. Hammer SM, et al. JAMA. 2006;296: Department of Health and Human Services. Available at: Accessed August 18, Allavena C, et al. J Acquir Immune Defic Syndr. 2005;39: Riddler SA, et al. New Engl J Med. 2008;358:

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Study Design Riddler SA, et al. N Engl J Med. 2008;358: Antiretroviral-naive HIV-infected patients with HIV-1 RNA ≥ 2000 copies/mL (N = 753) EFV 600 mg once daily + 2 NRTIs* (n = 250) LPV/RTV 400/100 mg twice daily + 2 NRTIs* (n = 253) EFV 600 mg once daily + LPV/RTV 533/133 mg twice daily (n = 250) Week 96 Stratified by HIV-1 RNA < or ≥ 100,000 copies/mL, presence or absence of chronic hepatitis infection (B, C, or both), and NRTI selection *NRTIs = 3TC 150 mg twice daily or 300 mg once daily plus either ZDV 300 mg twice daily, d4T extended release 100 mg once daily (participants < 60 kg received 75 mg once daily), or TDF 300 mg once daily.

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Eligibility  Inclusion criteria –13 years of age or older –Antiretroviral naive –HIV-1 RNA ≥ 2000 copies/mL within previous 60 days –Compliant with contraceptive use  Exclusion criteria –Previous ART for ≥ 7 days –Previous use of NNRTIs or lamivudine –Peripheral neuropathy ≥ grade 2 –Use of immunomodulators, vaccines, investigational therapies, human growth hormone, or within previous 30 days (exception: prednisone dose < 10 mg) –Drug/alcohol use/dependence affecting adherence –Recent drug-resistant HIV infection –Systemic treatment and/or hospitalization for severe medical illness within previous 14 days Riddler SA, et al. N Engl J Med. 2008;358:

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Main Findings  Significantly longer time to virologic failure for efavirenz plus 2 NRTIs vs lopinavir/ritonavir plus 2 NRTIs  No significant differences in time to virologic failure with either NRTI-containing regimen vs efavirenz plus lopinavir/ritonavir Riddler SA, et al. N Engl J Med. 2008;358: Time to Virologic Failure EFV + 2 NRTIs vs LPV/RTV + 2 NRTIs EFV + 2 NRTIs vs EFV + LPV/RTV LPV/RTV + 2 NRTIs vs EFV + LPV/RTV Hazard ratio (95% CI) 0.63 ( ) 0.86 ( )1.30 ( ) P value

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Main Findings (cont’d)  Time to virologic failure varied between treatment arms based on baseline HIV-1 RNA levels –Patients with HIV-1 RNA ≥ 100,000 copies/mL –Longer time to virologic failure for EFV plus 2 NRTIs vs LPV/RTV plus 2 NRTIs (P =.01) –Longer time to virologic failure for EFV plus 2 NRTIs vs EFV plus LPV/RTV (P =.02) –Patients with HIV-1 RNA < 100,000 copies/mL –Longer time to virologic failure for EFV plus LPV/RTV vs LPV/RTV plus 2 NRTIs (P =.02)  Time to regimen failure not significantly different between 3 arms –Trend toward longer time to regimen failure in EFV plus 2 NRTIs arm vs LPV/RTV plus 2 NRTIs arm (P =.03) Riddler SA, et al. N Engl J Med. 2008;358:

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Main Findings (cont’d)  Percentage of patients with HIV-1 RNA < 200 copies/mL or < 50 copies/mL at Wk 96 significantly higher with EFV plus 2 NRTIs vs LPV/RTV plus 2 NRTIs in intent-to-treat analysis where switches included and missing values censored EFV + 2 NRTIs (n = 250) LPV/RTV + 2 NRTIs (n = 253) EFV + LPV/RTV (n = 250) Patients (%) < 200 copies/mL< 50 copies/mL HIV-1 RNA Levels at Week 96 P =.04 P =.003 Riddler SA, et al. N Engl J Med. 2008;358:

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Main Findings (cont’d)  All 3 arms demonstrated increased CD4+ cell count with significantly higher increases in LPV/RTV-containing arms Riddler SA, et al. N Engl J Med. 2008;358: EFV + 2 NRTIs (n = 250) LPV/RTV + 2 NRTIs (n = 253) EFV + LPV/RTV (n = 250) P =.01 Median CD4+ Cell Count Increase at Week 96 (cells/mm 3 )

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Main Findings (cont’d)  Adherence similar between treatment arms  Time to first treatment-limiting toxicity similar between arms  More grade 3/4 laboratory events in EFV plus LPV/RTV arm resulting primarily from hypertriglyceridemia (P <.01 vs either NRTI-containing arm)  Statistically significant differences in median increase in limb fat from baseline between each group –EFV plus NRTIs (+0.05 kg) < LPV/RTV plus NRTIs (+0.7 kg) < EFV plus LPV/RTV (+1.15 kg) (P ≤.01 for each pairwise comparison) Riddler SA, et al. N Engl J Med. 2008;358:

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Other Outcomes  Genotypic resistance data (180/227 patients with virologic failure) –Incidence of any drug-resistance mutation or 2-class resistance higher in patients with virologic failure on EFV-containing regimens –NNRTI mutations more common when failing on EFV + LPV/RTV vs EFV + 2 NRTIs Riddler SA, et al. N Engl J Med. 2008;358: CharacteristicEFV + NRTIs (n = 250) LPV/RTV + NRTIs (n = 253) EFV + LPV/RTV (n = 250) Virologic failures, n Genotypic assays, n Any mutation (except minor protease mutations), %* NRTI mutations, % NNRTI mutations, % † Mutations in 2 drug classes, % ‡ 2617 EFV + LPV/RTV vs LPV/RTV + NRTIs, P <.001; EFV + NRTIs vs LPV/RTV + NRTIs, P =.002. †LPV/RTV + NRTIs vs EFV + NRTIs or EFV + LPV/RTV, P <.001. ‡LPV/RTV + NRTIs vs EFV + NRTIs, P <.001; EFV + NRTIs vs EFV + LPV/RTV, P =.01.

clinicaloptions.com/hiv ACTG 5142: Efavirenz vs Lopinavir/Ritonavir in Treatment-Naive Patients Summary of Key Conclusions  Virologic failure significantly more frequent and occurred more rapidly with LPV/RTV plus 2 NRTIs vs EFV plus 2 NRTIs in first-line ART –Virologic efficacy of efavirenz plus LPV/RTV similar to EFV plus 2 NRTIs –In patients with virologic failure, EFV-containing regimens associated with significantly higher rate of any drug resistance and 2-class resistance  CD4+ cell count increases from baseline at 96 weeks significantly higher in LPV/RTV-containing arms vs EFV plus 2 NRTIs arm Riddler SA, et al. N Engl J Med. 2008;358: