Human Immunodeficiency Virus (HIV) has evolved a number of mechanisms of evading the human immune system. One way is through a high level of mutation, which makes it difficult to develop a vaccine that stimulates protective immunity against all of the different HIV variants. Therefore, scientists are searching for a general surrogate marker that could be used to target any HIV-infected cell regardless of its mutational status. In this regard, scientists have recently turned their attention to the APOBEC machinery in HIV cells. APOBEC proteins are human proteins that modify genetic material of viruses so that they are unable to produce proteins essential for viral survival. Remarkably, HIV evades the APOBEC defense by making a protein called Vif that re-routes APOBEC proteins to proteosomes for destruction thereby reducing APOBEC's protective functions. However, this activity also increases the presentation of APOBEC antigens or peptides on the cell's surface. APOBEC peptides may be good candidates for surrogate HIV markers simply because they are present on the surface of all HIV-infected cells. In addition, in order for HIV-infected cells to stop displaying APOBEC peptides on their surface, the virus would need to evolve mutations in the region coding for the Vif protein that re-routes the APOBEC proteins. This would make the virus vulnerable to the defenses mediated by the functional APOBEC proteins. This phenomenon should result in dual pressure on the virus that should slow or prevent the evolution of viral resistance to these T-cell responses.