Blocking the PD-1 immune checkpoint protein triggers interferon-driven antiviral responses that measurably reduce latent HIV reservoirs in cancer patients already receiving this therapy. The treatment reprograms both innate and adaptive immune systems, with pre-existing type I interferon signatures predicting which patients experience the greatest reservoir decline, while elevated TGFβ signaling appears to counteract these benefits. This represents a significant advance in HIV cure research, as eliminating persistent viral reservoirs remains the primary obstacle to functional cure. PD-1 inhibitors like pembrolizumab and nivolumab are already FDA-approved for multiple cancers, potentially accelerating clinical translation. The interferon mechanism suggests these drugs work differently than traditional HIV therapeutics, which suppress viral replication but cannot clear dormant infected cells. However, the study's focus on cancer patients may limit generalizability, and the immune activation could pose risks in healthy HIV-positive individuals. The identification of predictive biomarkers like interferon signatures could enable personalized treatment approaches. While promising, this represents early-stage research requiring dedicated HIV cure trials to establish safety and efficacy in broader populations before clinical implementation.