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HIV-1 is a retrovirus that causes AIDS in humans. The RNA genome of the virus encodes a Gag polyprotein, which is further processed into matrix, capsid and nucleocapsid proteins. These proteins play a significant role at several steps in the viral life cycle. In addition, various stages of assembly, infection and replication of the virus involve necessary interactions with a large number of supplementary proteins/cofactors within the infected host cell. This minireview focuses on the proteomics of the capsid protein, its influence on the packaging of nonviral molecules into HIV-1 virions and the subsequent role of the molecules themselves. These interactions and their characterization present novel frontiers for the design and advancement of antiviral therapeutics.