Science and Education Publishing American Journal of Medical Case Reports 2374-216X 3 7 2015 06 10 Response to a Dolutegravir-based Regimen in an HIV-Infected Woman with Multiple Comorbidities and a Highly Resistant Strain 201 204 EN Amedeo Capetti 1st Division of Infectious Diseases, Luigi Sacco University Hospital, Milano, Italy Laura Carenzi Noemi Astuti Valeria Cozzi Valeria Micheli Maria Vittoria Cossu AJMCR2015375 10.12691/ajmcr-3-7-5 2015 02 27 2015 05 01 2015 06 10 HIV-infected patients have a higher burden of comorbidities than the general population and drug-drug interactions limit the choice of antiretroviral compounds, also limiting the possibility of drug sequencing in case of toxicity or failure. In our patient, affected by HIV-related pulmonary hypertension (HIV-PAH), the use of sildenafil and ambrisentan excluded the possibility of using two of the main classes of antiretrovirals, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Having failed a combination regimen based on raltegravir, while awaiting the results of genotypic testing for drug resistance she was switched to dolutegravir, a brand new integrase strand transfer inhibitor (INSTI) with high genetic barrier, and in one month her HIV-1 viremia dramatically dropped to undetectable levels. The genotypic test revealed resistance to all the drugs she was taking including dolutegravir. The backbone was changed to a dual regimen including rilpivirine and viral suppression was maintained at three months. Unprecedented pharmacokinetic data are provided for the two antiviral drugs in combination with sildenafil and ambrisentan.