The human immunodeficiency virus (HIV) belongs to the lentivirus a subgroup of Retroviruses belongs to the Retroviridae family that attacks the immune system. The last stage of HIV infection is AIDS. HIV is absurdly simple, albeit surprisingly complex. The virus is composed of nine genes encoding 15 different proteins. The literature has reported a large number of protein interactions of HIV and human proteins. Accordingly, many human host factors have been described to be important for HIV infection and replication. Systems biology (also known as Systeomics) is an approach to study systematically complex interactions within biological systems, and to integrate and analyze complex data sets from multiple experimental sources. Long-term non progressors are patients who remain AIDS-free for more than 10 years. In this group there are two subgroups: 1. virologic controllers who maintain the viral load below 2,000 RNA copies/mL and 2. elite controllers who have undetectable viral load or below 50 RNA copies/mL. Systems biology study of elite controllers provides an opportunity to analyze the immune system response which is uniquely endowed with the capacity to retain a long-term control of HIV replication.