125 Progress Toward A Cure for HIV

Combined antiretroviral therapy (cART) has dramatically increased life expectancy during HIV infection but must be taken life-long. Consequently, it carries problems of compliance, resistance, toxicity and cost. Finding a cure against HIV would resolve these issues. In theory, it could be either a “functional” or a “sterilizing” cure, but its main goal would be to keep HIV replication at bay without continuing cART. A couple of situations already exist where this has been achieved: -The Berlin patient who is free of cART more than 5 years following an allogenic bone marrow transplant from a donor with the delta 32 mutation on the CCR5 gene; -The “Mississippi child” who received cART within 31 hours after birth; -The “VISCONTI” patients who received cART at acute HIV infection and remained aviremic when this therapy was stopped a few years later; -Two patients who received allogenic stem cell transplantation for lymphomas and have no trace of HIV, although cART is still continued. Developing therapeutic strategies toward a HIV cure needs a deep understanding of the mechanisms that allow HIV persistence in reservoirs despite cART. Using current knowledge, approaches trying to purge the HIV reservoir have reached clinical trials using vorinostat. These trials showed the need of more potent activators combined with an immunologic intervention to eliminate cells where latent HIV has been activated. However, as the HIV reservoir is probably more complex than initially thought, others strategies than reactivation have to be pursued, including gene therapy.