Purpose of review: More than two decades after the recognition of HIV-1, not a single person has been cured. Although dramatic decreases in morbidity and mortality have been obtained with therapy, life-long antiretroviral therapy remains unrealistic for most patients. Replication-competent HIV-1 remains present in cellular and anatomical reservoirs even after years of undetectable viremia, leading to replication rebound each time therapy is interrupted. Advances have been made over the past few years in designing new potentially therapeutic avenues to overcome HIV persistence.
Recent findings: Although the first results obtained with non-specific immune stimulation, such as IL-2, have been disappointing in reducing the reservoir, several new drugs have been tested in vitro that could be of outstanding interest. These promising molecules include IL-7, prostratin, and HDAC inhibitors. The first clinical results using this last class of drugs have renewed optimism. Beside this approach, improvements have also been made in designing new tools to kill infected cells (immunotoxins), block HIV expression (RNA silencing), or control it (gene therapy).
Summary: This review focuses on the latest developments in the biology of HIV persistence, and envisages possible strategies to target HIV reservoirs. Currently available data allow the proposal of a combined and stepwise approach to be tested in several proof-of-concept trials.