A method of treating a subject at risk for having an HIV-1 virus infection, by administering to the subject a prophylactically effective amount of a composition comprising a CRISPR-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of the virus that is unique from the genome of the host cell, 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 and preventing HIV-1 retroviral infection.
