A personalized method of inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus, by determining a nucleic acid sequence of the HIV-1 proviral DNA harbored by a subject, designing two or more different multiplex guide RNAs (gRNAs) complementary to the HIV-1 proviral DNA sequences in the subject, administering to the subject a therapeutically effective amount of a composition comprising a CRISPR-associated endonuclease, and the two or more different multiplex gRNAs, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, and eradicating the HIV-1 proviral DNA from the host cell.
