The present study evaluated the frequency and receptor expression pattern of invariant natural killer T (iNKT) cells in human immunodeficiency virus (HIV)-infected individuals. Further, the effect of IL-15 + IL-12 stimulation on iNKT cells was also assessed. The study included 15 individuals each from normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals, and patients with HIV and tuberculosis coinfection (HIV-TB). The frequency of iNKT cells and the expression of phenotype, cytotoxic and chemokine receptors were studied by flow cytometry. The number of iNKT cells was significantly depleted in HIV and HIV-TB patients, which upon IL-15 + IL-12 stimulation expanded in HIV. The constitutively expressed natural cytotoxicity receptor, NKp46 was increased in HIV and HIV-TB, which might be the host's response to HIV replication. The distinct expression patterns of chemokine and adhesion receptors suggest that iNKT subsets might traffic to different microenvironment and tissues. High expression of chemokine receptor CCR5 by most iNKT cells suggests that these cells might be more favorable targets of HIV infection. Our results show that IL-15 and IL-12 combination has the ability to expand the selective depletion of iNKT cells in vitro in HIV-infected individuals, but of limited value when coinfected with TB.