Limited therapeutic options are available for patients with multidrug-resistant HIV. This report describes a 38-year-old female who was perinatally infected with HIV-1 and treated with 14 different antiretroviral regimens over 27 years, gradually leading to 4-class drug resistance. Despite various attempts to obtain sustained viral suppression, including the off-label administration of intravenous foscarnet and enfuvirtide, and thorough follow-up with 16 viral genotyping/phenotyping from 1999 to 2021, viral control was not maintained. Recently, the introduction of a regimen with fostemsavir and lenacapavir resulted in long-term viral suppression.