The role of immunodeficiency in the pathogenesis of both AIDS-defining and non-AIDS defining cancers cannot be over-emphasized. Multiple studies and meta-analyses show that risk of these malignancies exponentially rises as the CD4 cell counts fall. Furthermore, treatment of these cancers in patients who have HIV/AIDS is complex and challenging due to the underlying immunosuppression and risk for infections. Often, the diagnosis of some of these malignancies is made at the same time as the diagnosis of HIV/AIDS, which further complicates treatment decisions, especially when CD4 counts are extremely low. The risks of giving chemotherapy in the setting of severe immunosuppression warrants a paradigm shift in how we should be treating malignancies in patients with HIV/AIDS. We hypothesize and propose that alongside combination antiretroviral therapy (cART), some patients with HIV/AIDS associated malignancies should be treated with immunotherapy targeting PD-1/PD-L1 pathway rather than chemotherapy. The rationale and basis for the new approach is presented.
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