Enhanced Susceptibility of Human Immunodeficiency Virus Type 1 to Tipranavir in Treatment-Experienced Patients

Abstract

Abstract

We describe 2 highly treatment-experienced patients with unusual tipranavir susceptibility profiles. Patient 1 had a 5-year history of protease inhibitor exposure, and his genotype revealed multiple protease mutations interpreted as possible resistance to darunavir and tipranavir. Phenotypic testing, however, demonstrated susceptibility to darunavir and hypersusceptibility to tipranavir. Initiation of a new regimen of tenofovir/emtricitabine, efavirenz, tipranavir/ritonavir, and raltegravir provided a sustained immunologic and virologic response.

Patient 2 also had extensive prior protease inhibitor exposure and evolved high-level resistance to darunavir but maintaining full phenotypic sensitivity to tipranavir. Initiation of a new regimen (tipranavir/ritonavir and raltegravir, recycled zidovudine, lamivudine, tenofovir, and maraviroc) provided a fully suppressive virologic response.

The genotypic profiles of both patients included mutations that predict hypersusceptibility and improved response to tipranavir (24I, 50L/V, 54L, and 76V). In addition to using novel agents from new classes, clinicians should use updated resistance information for existing classes to create effective salvage regimens.