Oral oncolytic and antiretroviral therapy administration: dose adjustments, drug interactions, and other considerations for clinical use

Abstract

The rise in non-AIDS defining cancers (NADCs) is emerging as a leading cause of death for HIV and cancer patients. To address this, current literature and guidelines suggest the continuation of antiretroviral therapy (ART) with oral oncolytic agents to prevent adverse complications associated with HIV disease progression. However, such an approach has the potential for drug–drug interactions and adverse events for patients on such therapy. Further, recommendations on how to adjust these medications, when used concomitantly, are limited. As such, our purpose is to evaluate existing literature through such means as drug databases (e.g. Micromedex, Lexi-Comp, etc.) and package inserts along with PubMed/Medline, Embase, and Google Scholar databases to develop a reference tool for providers to utilize when there is a decision to treat a patient with ART and oral oncolytic agents concurrently. Our findings suggest that there are many drug interactions that should be taken into consideration with dual therapy. Metabolism is a key determinant of dose adjustment, and many oncolytic agents and ART agents must have their dose adjusted as such. Most notably, several tyrosine kinase inhibitors require dose increases when used with non-nucleoside reverse transcriptase inhibitors (NNRTIs) but must be decreased when used concomitantly with protease inhibitors (PIs) and cobicistat. Further findings suggest that certain agents should not be used together, which include, but are not limited to, such combinations as bosutinib with NNRTIs, cobicistat, or PIs; idelalisib with maraviroc or PIs; neratinib with NNRTIs, cobicistat, or PIs; and venetoclax with NNRTIs. Overall, the most prominent oncolytic drug interactions were discovered when such agents were used concomitantly with PIs, cobicistat-boosted elvitegravir, or NNRTIs. Future studies are necessary to further evaluate the use of these agents together in disease therapy to generate absolute evidence of such findings. However, from the studies evaluated, much evidence exists to suggest that concomitant therapy is not without drug interactions. As such, clinical decisions regarding concomitant therapy should be evaluated in which the risk and benefit of dual therapy are assessed. Dose adjustments must be made accordingly and in consultation with both HIV and oncology clinicians and pharmacists to reduce the risk for adverse outcomes and disease progression for those with cancer and HIV/AIDS.

Safety and efficacy of pharmacotherapy containing INSTIs and chemotherapy drugs in people living with HIV and concomitant colorectal cancer

“…Only 1 patient on the regimen of Lamivudine/Tenofovir/Lopinavir/Ritonavir developed severe nausea/vomiting and myelosuppression. Therefore, protease inhibitor-based regimens should be taken with caution in these patients, which is consistent with other findings [ 33 , 34 ].…”

Potential interactions between antineoplastic agents and medicines used to treat Covid-19

“…29 Lopinavir and ritonavir are potent inhibitors of CYP3A4, 30,31 which is the most abundant cytochrome P450 isoform in the human body and responsible for the metabolism of many drugs, 30 significantly affecting TKIs, particularly those used for the treatment of advanced lung cancer with activating mutations, malign hematologic neoplasms and breast cancer. 32 The findings show that atazanavir has one of the highest numbers of "contraindicated" and "major" DDI interactions when used in combination with antineoplastic agents. The drug is a protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV.…”

“…29 Lopinavir and ritonavir are potent inhibitors of CYP3A4, 30 , 31 which is the most abundant cytochrome P450 isoform in the human body and responsible for the metabolism of many drugs, 30 significantly affecting TKIs, particularly those used for the treatment of advanced lung cancer with activating mutations, malign hematologic neoplasms and breast cancer. 32 …”

Renal dysfunction among HIV patients under highly active antiretroviral therapy attending Kibagabaga district

“…Renal dysfunction among HIV patients under antiretroviral therapy The first described patient who was treated with tenofovir and developed reversible Fanconi syndrome, nephrogenic diabetes insipidus and ARF, Renal biopsy demonstrated cytoplasmic vacuolization, apical localization of nuclei and reduction of the brush border on proximal tubule epithelial cells [9].…”