The emergence of highly active antiretroviral therapy using combinations of reverse transcriptase and protease inhibitors ushered the dawn of a new era in management of human immunodeficiency virus infection. Immune reconstitution inflammatory syndrome is an adverse consequence of the restoration of pathogen-specific immune responses during the early phase of antiretroviral therapy. Pre-existing subclinical or opportunistic infections become apparent or even "worse" as host immunological inflammatory responses are "switched on". Major reductions in plasma viral load were associated with substantial increases in circulating CD4 T-cell lymphocyte counts and restoration of immune function. The rapid reversal in immune function gives rise to paradoxical therapeutic reaction by rebuilding host immune responses. Herein, a hidden culprit responsible for tuberculosis-associated immune reconstitution characterized by severe hypercalcemia and acute renal failure is reported, illustrating the compounded therapeutic strategy in AIDS patients.