A 29-year-old man with recently diagnosed HIV infection and a CD4 cell count of 225/mm³ began treatment with atazanavir (300 mg), ritonavir (100 mg), emtricitabine (200 mg), and tenofovir (300 mg) daily. For 18 months, he was treatment adherent and his plasma HIV RNA level was below the limit of detection. He then began a relationship with a new partner, who introduced him to methamphetamines. His medication adherence became erratic, and he missed appointments in clinic. Eventually. he was hospitalized for rehabilitation, and he resumed taking his medications on schedule. Following his discharge, he was found to have a plasma HIV RNA level of 11,400 copies/ml. Genotypic resistance testing revealed only an M184V mutation associated with emtricitabine resistance. A decision regarding his next treatment regimen needs to be made.