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Raltegravir-Based HAART Regimen in a Patient with Large B-Cell Lymphoma

Clinical Pharmacy Specialist in Internal Medicine/HIV; Clinical Associate Professor of Pharmacy; Clinical Assistant Professor of Internal Medicine/Division of Infectious Diseases, Department of Pharmacy, Virginia Commonwealth University Health System, Richmond, VA

Lauren Hynicka, PharmD

Assistant Professor of Pharmacotherapy, School of Pharmacy, University of Maryland, Baltimore, MD

Dwight Rackley, NP

Infectious Diseases/HIV Clinic, Virginia Commonwealth University Health System

Reprints: Dr. Fulco, Virginia Commonwealth University Health System, 401 N. 12th St., PO Box 980042, Richmond, VA 23298, fax 804/225-3920, pfulco{at}mcvh-vcu.edu

OBJECTIVE: To describe the antiretroviral management of a patient diagnosed simultaneously with HIV/AIDS and diffuse large B-cell lymphoma, focusing on the drug-drug interactions between highly active antiretroviral therapy (HAART) and concomitant cancer chemotherapy.

CASE SUMMARY: A 55-year-old white man was recently diagnosed with HIV/AIDS and presented 1 month later with complaints of nausea, vomiting, abdominal pain, double vision, right eye discomfort/swelling, and a 3.6-kg weight loss. An excisional biopsy of a right inguinal lymph node confirmed a new diagnosis of diffuse large B-cell lymphoma. HAART and a chemotherapeutic regimen, including cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with intrathecal methotrexate, was to be initiated. As the potential for multiple drug-drug interactions existed, raltegravir, abacavir, and lamivudine were chosen for the initial HAART regimen. The patient achieved and maintained an undetectable viral load throughout 6 CHOP cycles.

DISCUSSION: HAART improves the chemotherapeutic response in patients with HIV and lymphoma. Multiple drug-drug interactions are possible in patients who are to receive CHOP and HAART. Cyclophosphamide and vincristine are metabolized via the CYP3A4 isoenzyme. Protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors both inhibit and induce CYP3A4, with the potential for altered chemotherapeutic and cytotoxic effects. When PIs are combined with CHOP, mortality is reduced, but increased adverse effects are demonstrated. Raltegravir, an integrase inhibitor, is eliminated via glucuronidation and results in minimal drug-drug interactions. Raltegravir improves virologic and immunologic responses in HAART-naïve patients and thus would be a suitable alternative for preventing chemotherapeutic-HAART interactions.

CONCLUSIONS: There is limited information published regarding the potential for interactions between HAART and cancer chemotherapy. While further research is necessary, it is important for clinicians to consider the potential for drug-drug interactions when designing a HAART regimen concurrently with chemotherapy.

Key Words: abacavir, antiretroviral therapy, CYP3A4, diffuse large B-cell lymphoma, drug interactions, highly active antiretroviral therapy, integrase inhibitor, lamivudine, nonnucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, protease inhibitors, raltegravir, tumor lysis syndrome

Published Online, December 29, 2009. www.theannals.com, DOI 10.1345/aph.1M370