How far away is the functional cure of AIDS?

Due to the major breakthrough of anti AIDS drug treatment and the global promotion of free treatment program, AIDS has become a controllable disease from super cancer. However, drug treatment can only inhibit the virus replication, but can not eliminate the virus. Once the drug is stopped, the latent virus will replicate rapidly, so patients need to take medicine for life. The side effects, poor medication compliance and heavy economic burden caused by this have become obstacles to lifelong medication. By 2020, 38 countries in the world will not be able to afford up to $4.2 billion in drug treatment costs. The international consensus holds that the realization of functional cure of AIDS, that is, transforming life-long treatment into staged treatment, is a strategic problem of sustainable treatment to be solved urgently.

functional cure of AIDS refers to that after stopping antiviral treatment, HIV-1 in the patient’s body is still at the detection limit, and the number of CD4 + T lymphocytes and the immune function of the body maintain normal levels. Functional cure can effectively improve the immune function of patients, reduce the adverse reactions caused by long-term use of antiviral drugs, and greatly improve the quality of life of patients.

in the early stage of HIV-1 infection, a small number of infected CD4 + T cells will be transformed into memory cells, providing a latent place for HIV-1 virus and establishing a virus repository. Latent cells do not express HIV-1 virus antigen, so they can escape the pursuit of the immune system. The strategy of activating and killing HIV-1 virus is to activate latent HIV-1 virus through specific latent activator, and then use antiviral drugs or other combination therapy to kill infected cells, reduce or even eliminate the scale of HIV-1 virus repository, which is one of the research directions and hot spots of functional cure.

HIV-1 virus can attack CD4 + T lymphocytes with specific markers, resulting in massive cell death and severe immune impairment. This specific marker is known as the co receptor of HIV-1 virus. “Berlin patient” as the world recognized only cured AIDS patients, suffering from leukemia and AIDS at the same time, through the transplantation of CCR5 receptor mutation donor bone marrow, treatment of leukemia, at the same time, cured AIDS. This also gives scientists an important hint, through gene editing technology, make the body’s CD4 + T cells lack the entrance of HIV-1 virus, can resist virus infection, or can achieve the purpose of functional cure. However, the development and use of gene editing technology should take into account both ethical and security issues.

immunotherapy refers to the purpose of suppressing virus and controlling disease progression by artificially regulating the immune function of the body. As a new technology, immunotherapy has been applied in many fields, such as autoimmune diseases, tumors, and so on. Immunotherapy used in the field of AIDS includes therapeutic vaccine, broad-spectrum neutralizing antibody, HIV-1 specific T cell therapy, car-t cell therapy, immunomodulatory therapy, etc. Immunotherapy in primate animal models can effectively control the virus repository and inhibit the virus rebound after drug withdrawal. However, the existing research results show that it is difficult to completely inhibit the virus in the host by using only one immunotherapy method, and even has the risk of accelerating the replication and drug resistance of mutant strains. The combination of several immunotherapy strategies can greatly reduce the occurrence of this situation, which is conducive to achieve the purpose of functional cure.

to sum up, the main obstacle to achieve functional cure of AIDS is the existence of virus repository. With the continuous progress of research, more and more combination therapies have entered the stage of clinical trials, aiming to activate, reduce or even eliminate the virus repository, realize the functional cure of AIDS, and complete a qualitative breakthrough on the road of complete cure of AIDS. 08/16/2020