In this review, immune response and possible causes of depletion of CD4⁺ T-cell counts in patients with human immunodeficiency (HIV)-1 infection, have been documented. HIV has been recognized as a global problem; however, the developing countries are the most affected by epidemic diseases. Countries in the sub-Saharan Africa seem to bear the bulk of the HIV burden among the developing countries with about 24.7 million (≈ 63%) of all people living with HIV globally in 2006. The major factor obstructing progress towards an effective vaccine to prevent or modulate HIV - 1 infection is that the critical features needed for a protective immune response are not fully understood. Although, it has been found that potent neutralizing antibodies can protect against experimentally acquired HIV infection in animal models, they are scarcely generated in vivo in the infected person and neutralization resistant viral variants have been monitored to develop rapidly in chronic infection. It is generally believed that cellular immune responses, particularly specific cytotoxic T lymphocytes (CTL), are significant in the host response to HIV - 1 infection. Scientists have observed that CTL develop very early in acute HIV - 1 infection, coincident with a rapid fall in plasma vireamia, whereas in chronic infection their levels are inversely related to viral load. However the potent HIV-specific CTL response ultimately fails to control HIV replication. This could be as a consequence of the emergence of viral variants that escape CTL recognition or impairment of CTL function.