Drug interactions between HIV-associated lymphoma treatment and antiretroviral therapy
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Date
2019-11
Authors
Meyer, Lana
Journal Title
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Publisher
University of the Free State
Abstract
Despite the large-scale roll-out of ART in the mid-1990s, HIV and HIV-associated diseases remain a major health problem in South Africa. HIV-associated lymphoma contributes significantly to the morbidity and mortality of the HIV-positive population. The majority of HIV associated lymphomas are diffuse large B cell lymphomas (DLBCL), which have been reported to occur 60 to 200 times more commonly in patients with HIV than in the general population. Drug interactions are inevitable when treating HIV-associated lymphoma and can alter the efficacy of treatment and ultimately patient outcomes. Therapeutic questions have been raised pertaining to the need to find a balance between the administration of effective cytotoxic treatment and the effect it has on immune function. Complications such as infections and chemotherapeutic toxicity can occur. Dosing schedules may need to be adapted and certain combinations may be prohibited. The aim of this study was to conduct a critical overview of drug interactions between antiretroviral therapy used in the treatment of HIV and antineoplastic drugs used in the treatment of HIV-associated lymphoma. The purpose was to develop a quick reference tool to serve as a guide for clinicians to assist in identifying important drug interactions. Known drug interactions between 19 antiretroviral drugs and 13 antineoplastic agents used in the treatment of HIV and HIV-associated lymphoma respectively were investigated. Standard antiretroviral therapy (ART) regimens proposed by the national protocol were compared to drugs used in the following antineoplastic regimens: ABVD, CODOX-M-IVAC, CALGB9251, hyper- CVAD, dose adjusted R-EPOCH and R-CHOP. Data were obtained during March and April 2019 from three different internet-based drug interaction checkers, namely Medscape Drug Interaction Checker (https://reference.medscape.com/drug-interactionchecker), Lexicomp Online (https://www.wolterskluwercdi.com/lexicomp-online/) and RxList (https://www.rxlist.com/druginteraction-checker.htm). Interactions were classified as not clinically significant, no interaction, decreased or increased effect, contraindicated, increased toxicity, increased toxicity of both drugs due to synergism and loss of virological response. In total, 117 drug interactions were identified, of which 105 were deemed clinically significant. No interactions were found when the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine, abacavir and emtricitabine were used. The integrase inhibitors raltegravir and dolutegravir and the fusion inhibitor enfuvirtide also had no documented drug interactions. Chemotherapeutic agents that were found to have no significant drug reactions include cytarabine, rituximab and dacarbazine. Important drug interactions between the non- nucleoside reverse transcriptase inhibitors (NNRTIs) tenofovir and zidovudine and antineoplastic drugs were noted. Toxicity of tenofovir may be increased with concomitant use of bleomycin and ifosfomide. Caution must be taken when using zidovudine in combination with methotrexate, ifosfamide, vincristine and vinblastine, as the toxicity of both drugs is increased when used in combination. Efavirenz, a NNRTI, was found to have many interactions with antineoplastic drugs, the most significant being decreased levels of doxorubicin. Many drug interactions were noted between protease inhibitors and antineoplastic drugs. Anthracycline-associated cardiomyopathy may be induced when used concurrently with protease inhibitors. In general, rilpivirine is known to have a good side-effect profile. However, it must be noted that when combined with dexamethasone, this combination may lead to a loss of virologic response. Other significant interactions with drugs not included as standard ART is discussed in the article. Tailoring drug therapy according to individuals' specific requirements and proper medication reconciliation is critical when treating patients with HIV-associated lymphomas. Clinicians need to be aware of important interactions between antiretroviral therapy and antineoplastic drugs. Therapeutic monitoring and close interaction between role-players in the management of these patients is crucial. Communication between the clinic issuing the antiretroviral therapy, the attending haematologist or oncologist and the patient is vital to continuity of care. A quick referencing tool was developed as a guide to clinicians involved in the treatment of HIV associated lymphoma.
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Keywords
Dissertation (M.Med. (Internal Medicine) -- University of Free State, 2019, HIV-associated lymphoma, Chemotherapy, Drug interactions, Treatment regimens, Antiretroviral Therapy (ART), HIV/AIDS treatment and care