429. Clinical Significance of Drug-Drug Interactions in Patients Receiving HIV Antiretroviral Therapy & Cancer Chemotherapy
Session: Poster Abstract Session: HIV - Antiretroviral Therapy
Friday, October 21, 2011
Room: Poster Hall B1
Background: Patients with Human Immunodeficiency Virus (HIV) have an increased risk for malignancies due to underlying immunosuppression.  Also, as the lifespan of HIV patients has increased due to antiretroviral therapy (ART), age-related malignancies have increased.  Key ART components, protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRT) are associated with significant drug-drug interactions (DDI) due to inhibition and/or induction of cytochrome P450 (CYP) isoenzymes. However, limited information is available about the clinical significance of DDI between ART and antineoplastic agents. 

Methods: Study objectives were to identify potential DDI between ART and antineoplastic agents, evaluate the clinical significance of these DDI, and propose recommendations to mitigate such DDI.  Records of patients receiving concurrent ART and chemotherapy at Yale-New Haven Hospital were reviewed for modifications to chemotherapy and/or ART due to DDI. 

Results: Fifty-eight HIV patients receiving ART and chemotherapy from January 2000-July 2010 were retrospectively evaluated.  Patients received one or more of the following agents metabolized via CYP isoenzymes:  vinca alkaloids, taxols, capecitabine, cyclophosphamide, dacarbazine, etoposide and/or ifosfamide.  Ritonavir-boosted PI’s could inhibit CYP 3A4, 3A5, 2B6 and 2C8 and induce CYP 1A2 and 2C9.  Similarly, NNRTI’s could inhibit CYP 2C9 and 2B6 and induce CYP 3A4.  However, 80% of patients completed all cycles of chemotherapy without dose modification.  Ten patients had adjustments to chemotherapy or ART, but only two were directly attributed to DDI.  One patient’s ART was changed from an NNRTI to an integrase inhibitor to avoid a potential DDI of reduced chemotherapy efficacy. The other patient’s chemotherapy dose was reduced 50% due to severe mucositis and neutropenia attributed to a DDI between vincristine and ritonavir boosted PI-based ART. 

Conclusion: The majority of the putative drug-drug interactions were not observed.  To mitigate DDI, an integrase-based ART regimen in lieu of PI or NNRTI would avoid alterations in CYP activity. Prospective, controlled trials with pharmacokinetic sub-studies are needed to assess the impact of ART and chemotherapy DDI.


Subject Category: H. HIV/AIDS and other retroviruses

Kejal Patel, PharmD1, Joan Rivington, PharmD2, Trinh Pham, PharmD3, Osama Abdelghany, PharmD1 and Jeffrey Topal, MD4,5, (1)Pharmacy, Yale-New Haven Hospital, New Haven , CT, (2)Pharmacy, Yale-New Haven Hospital, New Haven, CT, (3)Pharmacy, University of Connecticut/Yale-New Haven Hospital, New haven, CT, (4)Yale-New Haven Hospital, New Haven, CT, (5)Section of Infectious Diseases, Yale School of Medicine, New Haven, CT

Disclosures:

K. Patel, None

J. Rivington, None

T. Pham, None

O. Abdelghany, None

J. Topal, None

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