Toward the Cure of HIV-1 Infection: Lessons Learned and Yet to be Learned as New Strategies are Developed.

Here, we review the progress that has been made in achieving a cure of HIV-1 infection. To date, this has only occurred in one person after he received allogeneic stem cell transplants from a CCR5 ∆32 homozygous donor in addition to chemotherapy and radiation to treat his acute myelocytic leukemia. The general consensus is that achieving a sustained remission of infection in the absence of antiretroviral therapy will involve a combination of strategies that involve both the targeting of the latent proviral genome and the induction of more effective anti-HIV-1 immune responses. Efforts to reverse HIV-1 proviral DNA integration in the host cell genome and those to enhance anti-HIV immunity have been disappointing thus far. The lack of clinically validated assays to measure both effects has hampered the development of effective therapies. We suggest the consideration of genome editing as a new approach to reduce the latently integrated proviral genome. In addition, new approaches to therapeutic immunization, alterations of immunoregulatory pathways, anti-HIV-1 antibodies, and anti-HIV-1 chimeric antigen receptor T lymphocytes are in development.