title: Nonnucleoside reverse transcriptase inhibitor resistance and the role of the second-generation agents.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  Clinical trials, resistance studies, and pharmacokinetic data were selected for review.
  
  
  RESULTS
  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.
authors.affiliation: Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Adams
authors.forename: Nimish
authors.initials: N
authors.lastname: Patel
authors.forename: Nancy
authors.initials: N
authors.lastname: Mankaryous
authors.forename: Mariam
authors.initials: M
authors.lastname: Tadros
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Miller
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors