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Titolo:
Measuring the effectiveness of antiretroviral agents
Autore:
Buss, N; Cammack, N;
Indirizzi:
F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland F Hoffmann La Roche & Co Ltd Basel Switzerland CH-4002 asel, Switzerland Roche Discovery, Welwyn Garden City, Herts, England Roche Discovery Welwyn Garden City Herts England en City, Herts, England
Titolo Testata:
ANTIVIRAL THERAPY
fascicolo: 1, volume: 6, anno: 2001,
pagine: 1 - 7
SICI:
1359-6535(200103)6:1<1:MTEOAA>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-PROTEASE INHIBITORS; BLOOD MONONUCLEAR-CELLS; IN-VITRO; ANTI-HIV; REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; PRIMARY INFECTION; RANDOMIZED TRIAL; DRUG-RESISTANCE;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
74
Recensione:
Indirizzi per estratti:
Indirizzo: Buss, N F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland F Hoffmann La Roche & Co Ltd Basel Switzerland CH-4002 itzerland
Citazione:
N. Buss e N. Cammack, "Measuring the effectiveness of antiretroviral agents", ANTIVIR TH, 6(1), 2001, pp. 1-7

Abstract

Considerable progress has been made recently in developing effective antiretroviral combination therapy that can suppress viral replication and delaydisease progression in individuals infected with HIV. A range of up to 15 approved antiretroviral agents is now available, which target two differentviral enzymes, while several agents are in clinical development. The rapiddevelopment and approval of antiretroviral agents, driven by the urgency of clinical need as well as the complexity of possible combinations, has precluded the extensive comparative clinical testing of regimens, which is necessary to establish the relative efficacy of various different agents. The lack of an appropriate animal model for HIV disease also increases relianceon in vitro measures. Several different in vitro and in vivo parameters have been defined in an attempt to quantify the effectiveness of antiretroviral agents, most importantly the 50% inhibitory and effective concentrations(IC50 and EC50). However, the clinical relevance of these measures is uncertain. Additionally, considerable variation exists in the usage of the terms 'IC50' and 'EC50' in recent publications in the literature. These issues pose interpretation problems to clinicians seeking information on the relative clinical efficacy of the agents. In this brief review, we attempt to clarify the different measures available and their potential utility for clinical decision-making, focusing particularly on the example of HIV protease inhibitors. There are many different quantifiable parameters that give information regarding the effectiveness of an antiviral drug. These include: inhibition of the viral target enzyme (inhibition constant, K-i); selectivityfor viral versus host enzymes; inhibition of viral replication in cell culture (IC50); ratio of efficacy to cytotoxicity in vitro (therapeutic index); inhibition of viral replication or symptoms in an appropriate animal model of the disease (EC50); and the effect on surrogate markers, such as viralload or CD4 cell count, after administration to humans (in vivo EC50). Each of these different parameters gives valid information about the properties of an antiretroviral agent, which can help to build up a picture of its potential clinical utility relative to other drugs. However, to gain meaningful results, it is important to apply this information intelligently, understanding the limitations of each parameter.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/06/20 alle ore 01:28:55