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

作者：Adams Jessica; Patel Nimish; Mankaryous Nancy; Tadros Mariam; Miller Christopher D^*

来源：Annals of Pharmacotherapy, 2010, 44(1): 157-165.

DOI：10.1345/aph.1M359

• diarylpyrimidine
• etravirine
• HIV
• NNRTI
• resistance
• rilpivirine

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.

• 出版日期2010-1