Cure and Long-Term Remission Strategies

The majority of virally suppressed individuals will experience rapid viral rebound upon antiretroviral therapy (ART) interruption, providing a strong rationale for the development of cure strategies. Moreover, despite ART virological control, HIV infection is still associated with chronic immune activation, inflammation, comorbidities, and accelerated aging. These effects are believed to be due, in part, to low-grade persistent transcription and trickling production of viral proteins from the pool of latent proviruses constituting the viral reservoir. In recent years there has been an increasing interest in developing what has been termed a functional cure for HIV. This approach entails the long-term, durable control of viral expression in the absence of therapy, preventing disease progression and transmission, despite the presence of detectable integrated proviruses. One such strategy, the block-and-lock approach for a functional cure, proposes the epigenetic silencing of proviral expression, locking the virus in a profound latent state, from which reactivation is very unlikely. The proof-of-concept for this approach was demonstrated with the use of a specific small molecule targeting HIV transcription. Here we review the principles behind the block-and-lock approach and some of the additional strategies proposed to silence HIV expression.