The invention pertains to compositions and methods for identifying gRNAs that are effective in treating a latent HIV infection. An embodiment of the invention provides a cell having incorporated into its genome: a gene that expresses a CRISPR-Cas protein and an HIV pseudovirus genome, wherein the HIV pseudovirus genome has a first marker gene encoding a first marker protein under the control of HIV-1 LTR promoter and a second marker gene inserted into the nef gene of the HIV pseudovirus and encoding a second marker protein under the control of a constitutive promoter. Screening methods for identifying gRNAs that can treat a latent HIV infection are also provided. Further, compositions comprising a CRISPR-Cas protein and gRNAs that can treat a latent HIV infection are provided. Furthermore, a method for treating a latent HIV infection in a subject by administering the compositions of CRISPR-Cas protein and gRNAs are described.
