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Lennox JL, Dejesus E, Berger DS, et al. Raltegravir versus Efavirenz Regimens in Treatment-Naíve HIV-1-Infected Patients: 96-Week Efficacy, Durability, Subgroup, Safety, and Metabolic Analyses. J Acquir Immune Defic Syndr 2010; 55:39-48.
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This study demonstrates the long-term antiretroviral activity of raltegravir Raltegravir was not only virologically noninferior to efavirenz but was also bettertolerated Liid abnormalities were less common in atients receiving raltegravir Patients in the raltegravir arm also gained less total body fat over 3 years
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Rockstroh JK, Lennox JL, DeJesus E, et al. Long-term Treatment With Raltegravir or Efavirenz Combined With Tenofovir/Emtricitabine for Treatment- Naive Human Immunodeficiency Virus-1-Infected Patients: 156-Week Results From STARTMRK. Clin Infect Dis 2011; 53:807-816. This study demonstrates the long-term antiretroviral activity of raltegravir. Raltegravir was not only virologically noninferior to efavirenz, but was also bettertolerated. Lipid abnormalities were less common in patients receiving raltegravir. Patients in the raltegravir arm also gained less total body fat over 3 years.
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Raltegravir (RAL)-based therapy demonstrates superior virologic suppression and immunologic response compared with efavirenz (efv)-based therapy with a favorable metabolic profile through 4 years in treatment-naíve patients: 192 Week results from startmrk [abstract 405
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DeJesus E, Rockstroh JK, Lennox JL, et al. Raltegravir (RAL)-based Therapy Demonstrates Superior Virologic Suppression and Immunologic Response Compared with Efavirenz (EFV)-based Therapy, with a Favorable Metabolic Profile, Through 4 Years in Treatment-naíve Patients: 192 Week Results from STARTMRK [Abstract 405]. In: IDSA 49th Annual Meeting. Boston; 20-23 October, 2011.
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Raltegravir once daily or twice daily in previously untreated patients with hiv-1: A randomized, active controlled, phase 3 noninferiority trial
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In this study once daily raltegravir took longer than twice-daily raltegravir to produce virologic suppression was more likely to result in virologic failure.Despite this 83.2% of participants in the once daily group achieve virologic suppression. This may be a treatment option for patients with a low viral load T-cell Count More Than 200 Cellsmlif No Other First-line Options Are Available
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Eron JJ JrRockstroh K Jr Reynes J et al. RaltegravirOnce Daily or Twice Daily in Previously Untreated Patients with HIV-1 a Randomized Active Controlled Phase 3 Noninferiority Trial. Lancet Infect Dis 2011; 11907-915. In this study once daily raltegravir took longer than twice-daily raltegravir to produce virologic suppression was more likely to result in virologic failure.Despite this 83.2% of participants in the once daily group achieve virologic suppression. This may be a treatment option for patients with a low viral load A T-cell Count More Than 200 Cellsmlif No Other First-line Options Are Available.
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Taiwo B, Zheng L, Gallien S, et al. Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262). AIDS 2011; 25:2113-2122. Once daily darunavir, when given with twice daily ritonavir, did not produce adequate virologic suppression.
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Jackson A, Watson V, Back D, et al. Plasma and intracellular Pharmacokinetics of Darunavir/Ritonavir once daily and Raltegravir once and twice daily in HIV-infected individuals. J Acquir Immune Defic Syndr 2011; 58:450-457.
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Of Noninferiority, Safety, and Tolerability of Lopinavir/ritonavir and Raltegravir Compared with Lopinavir/ritonavir and Tenofovir/Emtricitabine in Antiretroviral-Naive Subjects: The PROGRESS Study, 48-Week Results
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In This Small Trial The Fixed-dose Combination That Contained Elvitegravir Appeared Equivalent To A Fixed-dose Combination Containing Efavirenz. The Elvitegravir Containing Combination Was Also Better Tolerated. These Results Indicated That Thei 'Quad' pill had sufficient antiviral activity to move forward into larger clinical trials
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Cohen C, Elion R, Ruane P, et al. Randomized, Phase 2 Evaluation of Two Single Tablet Regimens Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Versus Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate for the initial treatment of HIV infection. AIDS 2011; 25:F7-F12. In this small trial the fixed-dose combination that contained elvitegravir appeared equivalent to a fixed-dose combination containing efavirenz. The elvitegravir containing combination was also better tolerated. These results indicated that the 'Quad' pill had sufficient antiviral activity to move forward into larger clinical trials.
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AIDS
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Cohen, C.1
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Elvitegravir cobicistatemtricitabine tenofovir (quad) has noninferior efficacy and favorable safety compared to efavirenzemtricitabinetenofovir in treatment-naíve hiv-1 Subjects [Abstract 101
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Sax P, DeJesus E, Mills A, et al. Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir (Quad) Has Noninferior Efficacy and Favorable Safety Compared to Efavirenz/Emtricitabine/Tenofovir in Treatment-Naíve HIV-1 Subjects [Abstract 101]. In: 19th Conference on Retroviruses and Opportunistic Infections. Seattle; 5-8 March, 2012.
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Week 48 results of an ongoing global phase 3 study comparing elvitegravircobicistatemtricitabine tenofovir disoproxil fumarate with atazanavirritonavir boosted plus emtricitabine tenofovir disoproxil fumarate in treatment naíve hiv-1 Subjects showing efficacy safety and pharmacokinetics [abstract 627
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DeJesus E, Rockstroh J, Henry K, et al. Week 48 Results of an Ongoing Global Phase 3 Study Comparing Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate with Atazanavir/Ritonavir Boosted Plus Emtricitabine/ Tenofovir Disoproxil Fumarate in Treatment Naíve HIV-1 Subjects Showing Efficacy, Safety, and Pharmacokinetics [Abstract 627]. In: 19th Conference on Retroviruses and Opportunistic Infections. Seattle; 5-8 March, 2012.
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In this dose ranging study, a 50 mg dose of dolutegravir given as monotherapy reduced viral load by greater than 1.5 log10. This result was achieved without any pharmacologic booster, and with once daily dosing of the dolutegravir. Lower doses of the dolutegravir were less effective, so the 50 mg dose moved forwardinto phase 2 clinical trials
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Min S, Sloan L, DeJesus E, et al. Antiviral Activity, Safety, and Pharmacokinetics/ Pharmacodynamics of Dolutegravir as 10 day monotherapy in HIV-1- infected adults. AIDS 2011; 25:1737-1745. In this dose ranging study, a 50 mg dose of dolutegravir given as monotherapy reduced viral load by greater than 1.5 log10. This result was achieved without any pharmacologic booster, and with once daily dosing of the dolutegravir. Lower doses of the dolutegravir were less effective, so the 50 mg dose moved forwardinto phase 2 clinical trials.
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van Lunzen J, Maggiolo F, Arribas JR, et al. Once Daily Dolutegravir (S/GSK 134-9572) in Combination Therapy in Antiretroviral-Naíve Adults with HIV: Planned Interim 48 Week Results from Spring-One, a Dose Ranging, Randomized, Phase 2b Trial. Lancet Infect Dis 2012; 12:111-118.
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