Fig. 1

Shock and kill therapies to cure HIV infection require the inhibition of Nef activity. Shock therapies aim to reactivate latent HIV (shock and to eliminate virus-producing cells (kill). Viral reactivation will enhance Nef activity to evade the immune surveillance system by decreasing cell surface levels of MHC-I on CD4⁺ T cells (+Nef). Evasion: the interaction between Nef and a Src Family Kinase (SFK) results in the intracellular retention of MHC-I. Subsequently, a CD8⁺T lymphocyte (CTL) will fail to recognize an HIV infected cell. Killing: conversely, the inhibition of Nef’s activity using molecular adjuvants, such as 2c-like compounds (red hexagon) that block the interaction between Nef and SFKs (−Nef) will restore cell surface levels of MHC-I which in turn will promote HIV antigen presentation (purple dot) and enhance susceptibility to HIV specific CD8⁺-CTL