A 31-year-old man with a CD4 count of 386 cells/mm³ took the antiretroviral regimen efavirenz-tenofovir DF-emtricitabine and did well on this regimen for about 18 months, with persistently undetectable HIV RNA levels. Subsequently, he had a 6-month period of problems with adherence and the HIV RNA level increased to 1,456 copies/mL. A genotype was performed and two significant mutations were identified: M184V and K103N. No other mutations are reported.