An HIV treatment strategy that combines CRISPR gene editing with antiretroviral drugs has proven effective in eliminating infection in mice, according to a study appearing in the Proceedings of the National Academy of Sciences this week. A functional cure of HIV has been documented in at least three cases, all of which involved allogenic hematopoietic stem-cell transplants, making them impractical for widespread use. Current standard HIV treatments comprise antiretroviral therapy (ART) with broadly neutralizing antibodies that can reduce infectious virus but not eliminate it since the virus establishes latency in certain immune cells. Aiming to overcome this barrier to a cure, a Temple University-led team led developed CRISPR-based drugs that target a key HIV coreceptor and a protein involved in viral assembly. They treated mouse models of human HIV infection with ART to suppress viral replication, followed by the CRISPR agents, which lead to viral elimination in tissue reservoirs of the infected animals with no signs of gene editing-related off-target effects. These results, the study's authors write, suggest that the approach could be translated to the clinic.