QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF For Our Patients Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Adams, J. Articles by Miller, C. D Search for Related Content PubMed PubMed Citation Articles by Adams, J. Articles by Miller, C. D

HIV/AIDS

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

Pharmacy Practice Resident, Henry Ford Hospital, Detroit, MI

Nimish Patel, PharmD

Infectious Diseases Research Fellow, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY

Nancy Mankaryous

PharmD Student, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences

Mariam Tadros

PharmD Student, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences

Christopher D Miller, PharmD

Assistant Professor, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences; Clinical Pharmacy Specialist, Division of HIV Medicine, Albany Medical College, Albany

Reprints: Dr. Miller, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, 106 New Scotland Ave., Albany, NY 12208, fax 518/694-7062, christopher.miller{at}acphs.edu

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-naïve 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

Published Online, December 8, 2009. www.theannals.com, DOI 10.1345/aph.1M359