Safety of raltegravir-based antiretroviral therapy in HIV-infected patients receiving multi-kinase inhibitors
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Background The risk of pharmacokinetic interaction is important in HIV-infected cancer patients receiving concomitantly highly active antiretroviral therapy (HAART) and anti-cancer systemic treatments. We aimed to evaluate the safety profile of raltegravir-based HAART in cancer patients receiving multi-kinase inhibitors (MKIs). Patients and Methods We conducted a retrospective medical record review of adult, HIV-infected cancer patients treated in our institutions from January 2010 to December 2015. Patients eligible for the present analysis were those receiving a raltegravir-based HAART at the time of the initiation of a MKI for the treatment of advanced solid tumors. Treatment-related toxicity, virological outcomes and pharmacokinetic profile of MKIs were examined. Results Twelve patients (7 males, median age 55 years) were identified. Seven had sarcoma/GIST, 3 had hepatocellular carcinoma, one had pancreatic neuroendocrine tumor, and one had NSCLC. Patients received the following MKIs: imatinib (n = 3), sorafenib (n = 3), pazopanib (n = 3), sunitinib (n = 2) and erlotinib (n = 1). The mean CD4+ count at baseline was 929 cells/mm3, and 860 cells/mm3 after completion of MKI treatment. In all patients, HIV viral loads remained below the limit of detection (40 copies/ mm3) during the whole MKI treatment. No virological failure occurred. No unexpected or serious adverse event related either to raltegravir-based HAART or to MKIs was observed. The trough plasma concentrations of MKIs were assessed in 8 patients, and were found normal in all but one case (not related to raltegravir-based HAART). Conclusions The present data represent the first documentation of the concomitant use of raltegravir-containing HAART and MKIs in HIV-infected adult patients with advanced non-AIDS defining malignancies, with a reassuring safety profile.
KeywordsCancer HIV Raltegravir Tyrosine kinase inhibitors Drug-drug interactions CYP3A4 Pharmacokinetics
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Conflicts of interest statement
Dr. Loulergue has acted as consultant for Pfizer.
Dr. Merad, Dr. Poinsignon and Prof. Gregory have no conflict of interest to declare.
Prof. Coriat has acted as consultant for Amgen, Bayer, Merck Serono, Novartis, Pfizer, Sanofi and Roche.
Prof. Ducreux has acted as consultant for Roche, Celgene, Merck Serono, Amgen, Sanofi, Novartis, Pfizer, Lilly, Servier.
Dr. Planchard has acted as consultant for Roche, GSK, Novartis, BMS and Astra-Zeneca.
Dr. Boige has acted as consultant for Merck Serono, Amgen, Sanofi-Aventis, Novartis and Bayer.
Dr. Le Cesne has acted as consultant for Amgen, Bayer, GSK, Lilly, Novartis, Pfizer, and PharmaMar.
Prof. Paci has acted as consultant for Amgen, BMS and Pierre Fabre.
Dr. Mir has acted as consultant for Astra-Zeneca, Amgen, Bayer, BMS, GSK, Lilly, Novartis, Pfizer and Roche.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.