A 39-year-old transgender woman with HIV and hepatitis B virus (HBV) coinfection starts on an antiretroviral regimen of dolutegravir plus tenofovir alafenamide-emtricitabine. She has not previously received antiviral treatment for either HIV or HBV. Baseline laboratory studies show a CD4 count of 102 cells/mm³, HIV RNA level of 86,000 copies/mL, HBV DNA level of 1,983,000 IU/mL, alanine aminotransferase (ALT) level of 58 U/L, and immunity to hepatitis A virus. Eight weeks after starting therapy, the HIV RNA level is 74 copies/mL, CD4 count is 255 cells/mm³, HBV DNA 88,560 is copies/mL, and ALT level is 126 U/L. Two weeks later, the ALT level increased to 168 U/L. At this point, she is asymptomatic. Immune reconstitution inflammatory syndrome (IRIS) is suspected as the cause of the increase in ALT levels.