Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat 
HIV-1-infected individuals; indeed most first-line antiretroviral therapies 
typically include one NNRTI in combination with two nucleoside analogs. In 2008, 
the next-generation NNRTI etravirine was approved for the treatment of 
HIV-infected antiretroviral therapy-experienced individuals, including those 
with prior NNRTI exposure. NNRTIs are also increasingly being included in 
strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to 
prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test 
whether a vaginal ring containing dapivirine can prevent HIV-1 infection in 
women; (3) a microbicide gel formulation containing the urea-PETT derivative 
MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, 
pharmacodynamics and acceptability; and (4) a long acting rilpivirine 
formulation is under-development for pre-exposure prophylaxis. Given their 
widespread use, particularly in resource-limited settings, as well as their low 
genetic barriers to resistance, there are concerns about overlapping resistance 
between the different NNRTIs. Consequently, a better understanding of the 
resistance and cross-resistance profiles among the NNRTI class is important for 
predicting response to treatment, and surveillance of transmitted 
drug-resistance.