Antiretroviral therapy (ART) has saved millions of lives, but is associated with numerous drawbacks including side-effects, drug resistance, and affordability. Thus, a high priority for the HIV field is the search for strategies to eliminate or control cellular HIV reservoirs, leading to long-term ART-free HIV remission. However, a number of challenges currently hinder our ability to design and test such novel therapies. Two of the most important problems are that: 1) It is unclear what the optimal surrogate endpoint should be for early-phase interventional HIV reservoir trials given our incomplete understanding of the relationship between HIV reservoir measures and the kinetics of viral rebound after treatment interruption;and 2) While there are individuals who can delay/control viremia after ART interruption, we have not yet identified the mechanisms underlying their post-treatment HIV control. Through the proposed studies, we plan to determine the combination of key viral reservoir measurements that best predict HIV rebound and provide an in-depth understanding of the virologic and immunologic mechanisms behind a remarkable cohort of post-treatment controllers. The results may accelerate the evaluation of novel HIV therapeutics and identify new targets for the next generation of HIV therapeutics focused on long-term drug-free HIV remission.
The persistence of HIV within long-lived reservoirs has far-reaching public health consequences, including the need for life-long antiretroviral treatment and the chronic inflammation that contributes to an increased risk of cardiovascular disease and other non-AIDS-defining conditions. One of the most important challenges to the HIV field is the development of drugs that deplete these HIV reservoirs with the eventual goal of achieving drug-free HIV remission. This study will determine factors that predict the timing and extent of HIV rebound after treatment interruption, which could lead to early markers of treatment efficacy and novel therapeutics aimed at a functional HIV cure.