Nonnucleoside Reverse Transcriptase Inhibitor Resistance and the Role of the Second-Generation Agents

被引：64

作者：

Adams, Jessica ^{[2
]}

Patel, Nimish

Mankaryous, Nancy ^{[1
]}

Tadros, Mariam ^{[1
]}

Miller, Christopher D. ^{[1
,3
]}

机构：

[1] Albany Coll Pharm & Hlth Sci, Dept Pharm Practice, Albany, NY 12208 USA

[2] Henry Ford Hosp, Detroit, MI 48202 USA

[3] Albany Med Coll, Div HIV Med, Albany, NY 12208 USA

来源：

ANNALS OF PHARMACOTHERAPY | 2010年 / 44卷 / 01期

关键词：

diarylpyrimidine; etravirine; HIV; NNRTI; resistance; rilpivirine; EXPERIENCED HIV-1-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS TYPE-1; TENOFOVIR DISOPROXIL FUMARATE; PLACEBO-CONTROLLED TRIAL; TREATMENT-NAIVE PATIENTS; CROSS-RESISTANCE; POSITIONAL ADAPTABILITY; ANTIRETROVIRAL THERAPY; ANTIVIRAL ACTIVITY; TMC125; ETRAVIRINE;

D O I：

10.1345/aph.1M359

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

OBJECTIVE: To review the current state of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance, discuss the promising role of second-generation NNRTIs, and provide insight into their clinical utility. DATA SOURCES: Articles were identified through searches of MEDLINE (May 2000-August 2009) and International Pharmaceutical Abstracts (May 1998-August 2009), using the key words etravirine, rilpivirine, TMC125, TMC278, diarylpyrimidine, NNRTI, and resistance. STUDY SELECTION AND DATA EXTRACTION: Clinical trials, resistance studies, and pharmacokinetic data were selected for review. DATA SYNTHESIS: NNRTIs are an integral class of antiretroviral agents utilized for the treatment of HIV-1 infection. These agents have become preferred therapy options for treatment-naive individuals per treatment guideline recommendations and have gained increased popularity over protease inhibitor-based antiretroviral therapy. However, available NNRTIs possess inherent characteristics, such as low genetic barrier to resistance and high degree of cross-resistance, that limit their use in HIV therapy. Due to the growing utilization of this highly efficacious antiretroviral class and the increased capability for resistance development, many HIV-infected patients have experienced treatment failure of an NNRTI. Cross-resistance makes other first-generation NNRTI agents unavailable for future use. Etravirine and rilpivirine are second-generation NNRTIs that are not significantly hampered by cross-resistance and possess potent antiretroviral activity against current NNRTI-resistant viral strains. These agents provide new and important therapy options for many HIV-infected patients. CONCLUSIONS: NNRTI resistance is an increasing problem that may impair the chances for therapeutic success in HIV-infected patients. Novel agents such as etravirine and rilpivirine provide new, sensitive options for patients and significantly improve the rate of virologic suppression when appropriately applied. KEY WORDS: diarylpyrimidine, etravirine, HIV, NNRTI, resistance, rilpivirine.

引用

页码：157 / 165

页数：9

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