Attacking the HIV reservoir from the immune and viral perspective

Upon HIV infection, a subset of latently infected cells carrying transcriptionally inactive integrated proviral DNA (the HIV-1 reservoir) is rapidly established. These cells are the main force behind HIV persistence under highly active antiretroviral therapy (HAART), which only impacts on actively replicating viruses and it is therefore unable to eradicate the infection. However, the case of Timothy Brown, also known as the Berlin patient, demonstrates that eradication is possible, and recent data support the idea that latency may be reverted in vivo, suggesting that it is possible to perturb the HIV-1 reservoir. This may be achieved by implementing both pharmacological and immunological strategies to reactivate HIV-1 from latently infected cells. Nevertheless, reactivation might not be sufficient to eradicate the virus. Reinforcing HIV-1-specific immune responses and blocking potential new events of viral replication will probably help reaching the final goal of eradication or the alternative objective of a functional cure for HIV-1.