title: Safety of raltegravir-based antiretroviral therapy in HIV-infected patients receiving multi-kinase inhibitors.
abstract: 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/mm3after 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.
authors.affiliation: Teaching Hospital Cochin, CIC Cochin-Pasteur, INSERM CIC1417, Assistance Publique - Hôpitaux de Paris, University Paris Descartes, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Loulergue
authors.affiliation: Department of Emergency and Ambulatory Care, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Mansouria
authors.initials: M
authors.lastname: Merad
authors.affiliation: Department of Gastroenterology and Digestive Oncology, Teaching Hospital Cochin, Assistance Publique - Hôpitaux de Paris, University Paris Descartes, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Coriat
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94800, Villejuif, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94800, Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94800, Villejuif, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Boige
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94800, Villejuif, France.
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.affiliation: Department of Orthopaedic Surgery, Teaching Hospital Avicenne, Assistance Publique - Hôpitaux de Paris, University Paris XIII, Bobigny, France.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Gregory
authors.affiliation: Department of Pharmacology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Vianney
authors.initials: V
authors.lastname: Poinsignon
authors.affiliation: Department of Pharmacology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.affiliation: Department of Cancer Medicine, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94800, Villejuif, France. olivier.mir@gustaveroussy.fr.|Department of Pharmacology, Gustave Roussy Cancer Campus, Villejuif, France. olivier.mir@gustaveroussy.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mir
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068898:Raltegravir Potassium / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068898:Raltegravir Potassium
keywords: CYP3A4; Cancer; Drug-drug interactions; HIV; Pharmacokinetics; Raltegravir; Tyrosine kinase inhibitors