Coronary artery disease (CAD) is amongst the leading causes of death in human immunodeficiency virus (HIV)-infected persons. Severe left main disease (LMD) occurs in approximately five percent of HIV-infected patients, with chronic total occlusion (CTO) of this vessel being an even rarer phenomenon. We describe a non-adherent HIV-infected patient with a left main coronary artery (LMCA) CTO that presented with heart failure with mildly reduced ejection fraction (HFrEF) and ventricular tachycardia (VT).