Combination of broadly neutralizing HIV antibodies and viral inducers
The present invention relates to methods and agents for preventing the establishment of HIV-1 latent reservoirs or for reducing the size of the reservoirs. Specifically, the disclosure provides methods and agents for preventing the establishment of HIV-1 latent reservoirs or for reducing the size of the reservoirs, the methods comprising administering to the subject a therapeutically effective amount of an isolated anti-HIV antibody, and administering to the subject two or more viral transcription inducers in effective amounts to induce transcription of an HIV provirus in the cells. Further provided are antibodies and viral transcription inducers used in the methods.
1. A method for decreasing the size of or preventing the establishment of a latent reservoir of HIV infected cells in a subject in need thereof, comprising
administering to said subject a therapeutically effective amount of an isolated anti-HIV antibody selected from the group consisting of 3BNC117 and 10-1074, and
administering to said subject two or more viral transcription inducers in effective amounts to induce transcription of an HIV provirus in said cells.
2. The method of claim 1 , wherein the antibody is a human antibody, a humanized antibody, a humanized antibody, or a chimeric antibody.
3. The method of claim 1 , wherein the transcription inducers are selected from the group consisting of vorinostat, an HDAC inhibitor, I-BET151, a BET bromodomain inhibitor, αCTLA4, and a T-cell inhibitory pathway blocker.
4. The method of claim 1 , wherein said cells comprise CD4 + T cells.
5. The method of claim 1 , wherein the antibody or antibodies are administered to the subject within about 96 hours after exposure to HIV.
6. The method of claim 1 , further comprising administering to said subject an antiviral agent.
7. The method of claim 5 , wherein the antiviral agent is selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an entry or fusion inhibitor, and an integrase inhibitor.
8. A method for preventing the establishment of a latent reservoir of HIV infected cells in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of an isolated anti-HIV antibody, wherein the isolated anti-HIV antibody is selected from the group consisting of 3BNC117 and 10-1074.
9. The method of claim 8 , wherein the antibody is a human antibody, a humanized antibody, or a chimeric antibody.
10. The method of claim 8 , wherein two or more of said antibodies 3BNC117 or 10-1074are administered to said subject.
11. The method of claim 8 , wherein the antibody or antibodies are administered to the subject within about 96 hours after exposure to HIV.