The NEAT Study: A 48-Week Open-Label Study to Compare the Antiviral Efficacy and Safety of GW433908 Versus Nelfinavir in Antiretroviral Therapy???Naive HIV-1-Infected Patients

Rodríguez-French, A; Boghossian, Jack; Gray, Glenda; Nadler, Jeffrey P.; Quinones, Arnaldo R; Sepulveda, Gladys; Millard, Judith; Wannamaker, Paul

doi:10.1097/00126334-200401010-00003

Cited by 130 publications

(81 citation statements)

References 11 publications

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“…FPV can replace APV based upon comparable plasma APV exposures achieved for molar equivalent FPV and APV dosage regimens (5), comparable plasma APV exposures achieved for molar equivalent FPV-RTV and APV-RTV dosage regimens (as demonstrated in this study), data supporting the hypothesis that metabolic drug interactions established for APV can be extrapolated to FPV (as demonstrated in this study), similar antiviral activity over 4 weeks of dosing with FPV or APV in antiretroviral-naïve HIV-1-infected patients (5), robust clinical trials demonstrating the safety and efficacy of FPV (2,3), and an adverse event profile for FPV that is similar to or better than that observed with APV (2,3,5).…”

Section: Fosamprenavir (Fpv) Is a Human Immunodeficiency Virus Type 1supporting

confidence: 79%

Ritonavir Increases Plasma Amprenavir (APV) Exposure to a Similar Extent when Coadministered with either Fosamprenavir or APV

Wire

Baker

Jones

et al. 2006

Antimicrob Agents Chemother

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To compare the effect of ritonavir on plasma amprenavir pharmacokinetics, healthy adults received either fosamprenavir (700 mg twice a day [BID]) or amprenavir (600 mg BID) alone and in combination with ritonavir (100 mg BID). Ritonavir increased plasma amprenavir pharmacokinetic parameters to a similar extent when coadministered with either fosamprenavir or amprenavir.Fosamprenavir (FPV) is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor approved in the United States (as Lexiva), the European Union (as Telzir), and in other countries for the treatment of HIV-1 infection in combination with other antiretroviral agents. FPV has demonstrated antiviral efficacy, durability, and tolerability in antiretroviral therapy-naïve (2, 3) and protease inhibitor-experienced subjects (R. C. Elston, P. Yates, M. Tisdale, N. Richards, S. White, and E. DeJesus, Abstr. XV Int. AIDS Conf., abstr. MoOrB1055, 2004. FPV, the phosphate ester prodrug of amprenavir (APV), is rapidly and extensively converted to APV in vivo (1, 5). FPV was developed to replace the large capsule, high pill burden, and undesirable excipient requirements associated with the previous soft-gelatin capsule formulation of APV (Agenerse).Similar plasma APV exposures are observed for equimolar FPV-ritonavir (RTV) and APV-RTV regimens across pharmacokinetic studies (4, 6), suggesting that RTV has similar effects on plasma APV pharmacokinetics when coadministered with either FPV or APV; however, the specific drug interaction between FPV and RTV had not been tested formally. Thus, this study was designed to assess the effect of RTV on plasma APV pharmacokinetics following coadministration with FPV at 700 mg twice a day (BID) and following coadministration with APV at 600 mg BID.In this randomized, open-label, two-period, 2 ϫ 2 crossover study, healthy subjects received either FPV at 700 mg BID and FPV at 700 mg BID plus RTV at 100 mg BID or APV at 600 mg BID and APV at 600 mg BID plus RTV at 100 mg BID for 14 days during confinement, with a 28-day washout between treatments. On day 14, fasting plasma pharmacokinetic samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, and 12 h after morning dosing. Samples were analyzed for APV and FPV concentrations by Advion Biosciences (Ithaca, NY) using validated high-performance liquid chromatography with tandem mass spectrometry for detection following solid-phase extraction (lower limit of quantification of 10 ng/ml for APV; bias, Յ11% [accuracy], and coefficient of variation, Ͻ8% [precision]; lower limit of quantification of 5 ng/ml for FPV; bias, Յ2% [accuracy], and coefficient of variation,Pharmacokinetic analysis of plasma APV concentration-time data was conducted using the noncompartmental model 200 (for extravascular administration) of WinNonlin (version 3.1) Software (Pharsight Corporation, Mountain View, CA). Plasma APV area under the curve at steady state (AUC ,ss ), maximum concentration at steady state (C max,ss ), time to C max (T max,ss ), and concentration at the end o...

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Section: Fosamprenavir (Fpv) Is a Human Immunodeficiency Virus Type 1supporting

confidence: 79%

Ritonavir Increases Plasma Amprenavir (APV) Exposure to a Similar Extent when Coadministered with either Fosamprenavir or APV

Wire

Baker

Jones

et al. 2006

Antimicrob Agents Chemother

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“…Incidence of diarrhea with FPV was significantly less than with NFV when the 2 agents were compared as part of combination therapy. 48,50,51 The incidence of all other reported adverse effects were similar between FPV and NFV. Tolerability of FPV was comparable to that of APV.…”

Section: Adverse Drug Reactionsmentioning

confidence: 83%

“…In both trials FPV was compared with twice-daily NFV when either agent was given as part of combination therapy with ABC and 3TC. 50,51 In one trial, a greater proportion of patients receiving FPV twice daily achieved the desired virologic response when compared with NFV twice daily. 50 In the second trial, the desired antiretroviral response was similar when oncedaily FPV plus low-dose RTV was compared with twice-daily NFV; however, more patients in the NFV group experienced virologic failure.…”

Section: Efficacymentioning

confidence: 99%

New Antiretroviral Therapies for Pediatric HIV Infection

Morris¹,

Kraus

2005

The Journal of Pediatric Pharmacology and Therapeutics

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Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection.

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“…The NEAT trial 49 was an international, multicenter, randomized, open-label study that compared the efficacy, durability, and tolerability of unboosted fos-amprenavir (f-AMV) Dovepress 1400 mg twice daily, with nelfinavir (NFV) 1250 mg twice daily, in antiretroviral therapy (ART)-naive HIV-infected adults with plasma viral load at screening greater than or equal to 5000 copies/mL. Patients were randomly assigned to f-AMV or NFV (2:1) for a minimum of 48 weeks, with a background of ABC and 3TC.…”

Section: Abc/3tc As Separate Agents Combined With a Pi Or Nnrtimentioning

confidence: 99%

Abacavir/lamivudine combination in the treatment of HIV: a review

Sivasubramanian

Frempong-Manso

MacArthur

2010

TCRM

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The NEAT Study: A 48-Week Open-Label Study to Compare the Antiviral Efficacy and Safety of GW433908 Versus Nelfinavir in Antiretroviral Therapy???Naive HIV-1-Infected Patients

Abstract: Administration of 908 BID resulted in a potent and sustained antiretroviral response, notably in ART-naive patients with advanced HIV disease. GW433908 was generally well tolerated and provides a convenient dosing option without food or fluid restrictions.

Cited by 130 publications

References 11 publications

Ritonavir Increases Plasma Amprenavir (APV) Exposure to a Similar Extent when Coadministered with either Fosamprenavir or APV

Ritonavir Increases Plasma Amprenavir (APV) Exposure to a Similar Extent when Coadministered with either Fosamprenavir or APV

New Antiretroviral Therapies for Pediatric HIV Infection

Abacavir/lamivudine combination in the treatment of HIV: a review

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