Though many are familiar with human immunodeficiency virus (HIV) for its role in causing acquired immunodeficiency syndrome (AIDS), patients on antiretroviral therapy (ART) still show immune symptoms even with undetectable viral load. In this journal club, a presenter discusses landmark papers revealing that certain types of HIV infection can trigger pyroptosis, a highly pro-inflammatory programmed cell death pathway. Infection can also lead to depletion of CD4+ T cells in the gut and disrupt integrity of the epithelium in the lamina propria, causing infiltration of the microbiota. The resulting inflammation can cause severe issues even for patients who have their HIV infection under control with ART. The presenter proposes new therapeutics that inhibit caspase-1 or other components of the pyroptosis pathway to alleviate this inflammation.