Targeted therapies to treat non-AIDS-defining cancers in patients with HIV on HAART therapy: treatment considerations and research outlook

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Abstract
Purpose of review Highly active antiretroviral therapy has led to a dramatic improvement in the prognosis of patients diagnosed with HIV and AIDS. This includes a significant decline in the rates of AIDS-related cancers, including Kaposi's sarcoma and non-Hodgkin's lymphoma. Unfortunately, rates of non-AIDS-defining cancers are on the rise, and now exceed the rates of AIDS-related cancers in patients with HIV. Treating non-AIDS-defining cancers in patients who are on highly active antiretroviral therapy is an open and complicated clinical question. Recent findings Newer targeted therapies are now available to treat cancers which were historically refractory to traditional cytotoxic chemotherapy. Highly active antiretroviral therapy agents are notorious for causing drug–drug interactions. The co-administration of targeted chemotherapies with highly active antiretroviral therapy could well impede the efficacy or increase the toxicity of these targeted therapies. Unfortunately little is known about possible drug–drug interactions because HIV patients are typically excluded from clinical trials. Summary We highlight what is known about how and why highly active antiretroviral therapy agents can affect drug metabolism. We then present the clinical and pharmacological data for nine recently approved targeted therapies – imatinib, dasatinib, nilotinib, erlotinib, sunitinib, lapatinib, bortezomib, sorafenib, and temsirolimus. We conclude with considerations on how to use these new agents to treat non-AIDS-defining cancers, and discuss a future research agenda to better understand and predict potential highly active antiretroviral therapy-targeted therapy interactions.