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.