The investigation of novel and innovative treatment approaches for long-term management of HIV-infection has intensified due to the growing number of infected individuals worldwide and the constraints of resistance, toxicity and inconvenience associated with lifelong therapy. Current treatment relies entirely on antiretroviral drugs targeting various stages of the life cycle of HIV, rather than on leveraging the immune system. However, the boosting of HIV-specific immune responses in chronic infection offers a vast potential for synergy with antiretroviral drugs, thereby contributing to durable control of viral replication. A novel immunotherapeutic agent that delivers plasmid DNA to dendritic cells after topical skin application is the first therapeutic vaccine that has demonstrated immunological and clinical benefit in chronically infected rhesus macaques in combination with antiretroviral therapy.