Chemotherapy Toxicity Occurrence with Concomitant Antiretroviral Therapy in Patients with Lymphoma,

Patients with HIV/AIDS are at high risk for developing oncologic diseases such as lymphomas. Since the mid-1990s, the implementation of combined antiretroviral therapy (cART) has decreased the incidence of AIDS-defining malignancies; however, the advent of chronic, controlled HIV infection has increased the incidence of non-AIDS-defining malignancies such as Hodgkin Lymphoma (HL). Mortality from HL and non-Hodgkin Lymphoma (NHL) has decreased with the addition of cART to traditional and dose-adjusted chemotherapy regimens. Many antiretroviral agents affect the metabolism of antineoplastic agents via cytochrome P450 interactions. Possible complications include decreased efficacy of antineoplastic agents and increased toxicity of either or both classes of drugs. Protease inhibitors, especially ritonavir, are potent CYP3A4 inhibitors and therefore have the potential to significantly increase toxicity of multiple antineoplastic agents. Excess neutropenia has been observed in prospective studies in concomitantly treated patients when protease inhibitors are included in cART. Despite this, there is currently no clear evidence to guide clinicians on how to dose pharmacologic agents to treat HIV/AIDS and lymphoma simultaneously. The purpose of this retrospective chart review was to evaluate the significance of the drug-drug interactions experienced by HIV/AIDS patients who were treated with antiretroviral agents and high-intensity chemotherapy for lymphoma.

All patients treated at Hennepin County Medical Center from 1999–2010 were screened for the diagnoses of lymphoma and HIV/AIDS. Patients were included if they met the following criteria: age greater than 18 years; diagnosis of HIV or AIDS; diagnosis of lymphoma; and treatment with an antineoplastic regimen for lymphoma with concomitant antiretroviral therapy. Electronic medical records were systematically reviewed for patient demographics, CD4 counts, viral loads, complete blood counts, complete metabolic panels, planned chemotherapy regimens, and chemotherapy administration and discontinuation. Chemotherapy adverse drug reactions (ADRs) were recorded and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Medication profiles for each patient were screened for potential drug interactions. The primary outcomes were incidence of chemotherapy interruptions or changes due to toxicity and the time to such regimen changes. The secondary outcomes were the number of ADRs reported and the management of these events.

A total of 114 patients were identified as having both an HIV/AIDS diagnosis and an oncologic diagnosis, 31 of which were lymphomas. Eleven of the 31 patients received concomitant antiretroviral therapy and had medical records available for review, encompassing 7 chemotherapy regimens and 12 chemotherapy courses. Median age was 46 years and 9 of the patients were male. All chemotherapy courses were subject to potential drug-drug interactions with patients' cART with 10 courses potentially affected by the use of protease inhibitors in 9 patients. Delay or interruption due to chemotherapy toxicity occurred in 11 of 12 chemotherapy courses affecting 10 patients as early as before the completion of their first chemotherapy cycle and as late as their last chemotherapy cycle. The 11 patients experienced a total of 124 documented ADRs (16 grade III-V), and 10 patients had a total of 20 emergency department visits. Eight patients required hospitalization 16 times for management of their ADRs. One patient with Castleman disease died of cytokine release syndrome in spite of chemotherapy.

Chemotherapy interruptions and delays may be common in the setting of concomitant antineoplastic and antiretroviral therapy for treatment of lymphoma and HIV/AIDS. Although most chemotherapy ADRs were grade I or II, concomitant cART may have contributed to the increased hospitalization rate of these patients. Further investigation is required to determine if risk-mitigation strategies such as chemotherapy dose-reduction, avoidance of cART regimens which include protease inhibitors, and therapeutic drug monitoring should be implemented.

No relevant conflicts of interest to declare.