Targeting the latent reservoir to achieve functional HIV cure

Abstract

While highly active anti-retroviral therapy has greatly improved the lives of HIV-infected individuals, current treatments are unable to completely eradicate the virus. This is due to the presence of HIV latently infected cells which harbor transcriptionally silent HIV. Latent HIV does not replicate or produce viral proteins, thereby preventing efficient targeting by anti-retroviral drugs. Strategies to target the HIV latent reservoir include viral reactivation, enhancing host defense mechanisms, keeping latent HIV silent, and using gene therapy techniques to knock out or reactivate latent HIV. While research into each of these areas has yielded promising results, currently no one mechanism eradicates latent HIV. Instead, combinations of these approaches should be considered for a potential HIV functional cure.

Keywords: HIV; gene therapy; host defense mechanisms; latent HIV; targeting latent HIV; viral reactivation.

Figure 1.. Four main approaches that target the latent reservoir of HIV

Four research areas, which reactivate HIV (1. shock), eliminate HIV (2. kill), silence HIV (3. silence), or alter the immune system to resist HIV (4. gene therapy) should contribute to the functional or complete cure of HIV in infected individuals. Within each area are individual components of that therapy. They can be applied individually or in combinations, which should decrease their doses and deleterious effects. Most likely, there will be additional approaches in the future.