HIV感染 z-bo 2020-11-13 360

　　"Excellent", "Exactly for the first time", "Attractive", "Too shocking and therefore very unreal", these are the controversial and puzzling researcher The monkey’s research results show that monoclonal antibodies used to treat human inflammatory bowel disease may have a "functional" cure for HIV infection.

　　HIV treatment has been greatly improved. The combined use of antiretroviral (ARV) drugs can routinely eliminate the HIV virus. This therapy is so effective that standard tests in the blood cannot detect the virus. Researchers are looking for a long-term treatment strategy that allows the infected person to stop taking antiretroviral drugs while the HIV virus does not re-emerge, because antiretroviral drug treatment is only a functional cure, far from a complete cure, and the virus is still latent in the patient's body , These viruses can integrate their genes into the DNA of the host cell. However, with the exception of a few notable cases, the vast majority of patients who stop taking antiretroviral drugs will have their virus counts spiked to high levels after a few weeks. Therefore, in order to suppress the growth of the virus, AIDS-infected patients must take antiretroviral drugs for life.

　　Today in Science, a team led by Aftab Ansari, an immunologist at Emory University School of Medicine in Atlanta, described eight monkeys infected with SIV. SIV is the monkey's form of HIV. They allowed eight monkeys to receive antiretroviral drug treatment and at the same time inject them with an antibody that is similar to an approved drug for the treatment of Crohn’s disease and ulcerative colitis. Its target receptor is The surface of immune cells is called α4ß7. The combination of antiretroviral drugs and antibodies was discontinued after nine months of treatment. Eight monkeys had only low levels of HIV detected in their blood or undetectable monkeys. Seven monkeys infected with SIV in the control group received the same dose of placebo antibody, and the virus count would rebound to a high level within two weeks of stopping antiretroviral drugs. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, immunologist and co-author of the paper, said: "The results shocked us. They are so amazing."

　　Ansari emphasized: Animals treated with anti-α4ß7 may still be infected. "They have not been cured, and they are far from being completely cured," Ansari preached. In addition, he and Fauci do not yet know how effective this treatment strategy is. "It made us think more than 10 times, ‘what exactly happened in this system?’" Ansari said. "This is really a mystery."

　　Ansari, Fauci, and other AIDS researchers are fascinated by α4ß7 because it is found on the surface of CD4 cells, which are the main targets of the HIV virus. This protein helps CD4 cells to gather in the intestine and reach a high cell mass. Unfortunately, α4ß7 can also bind to HIV cell surface proteins, making CD4 cells more susceptible to infection, which explains why the virus destroys intestinal cells in the early stages of infection. Ansari and Fauci were also attracted by the results of their early monkey experiments, which showed that the α4ß7 antibody can prevent SIV infection. They proposed a simple and easy-to-understand protection mechanism: the antibody reduces the tendency of CD4 cells to accumulate in the intestine, thereby making the AIDS virus attack fewer targets in the intestine.

　　Strangely, in the new experiment, the CD4 cells in the monkey’s intestine are inlaid with higher levels of α4ß7. A new positron emission tomography/computed tomography technology reveals that by displaying labeled viruses: animals treated with anti-α4ß7 have higher levels of SIV virus in certain parts of the body than control animals, such as the small intestine . The treated monkeys did show signs of immune response, which helped them control the SIV virus, but these immune responses were not very strong.

　　Steven Deeks, a clinician who conducts research on HIV treatment at the University of California in San Francisco, said: "Everything they expected did not happen, but what has happened is very interesting." "The immune system is unknowable, dynamic, and complex. , It always surprises you."

　　Although there is no clear mechanism, immunologist Rafick-Pierre Sékaly of Case Western Reserve University in Cleveland, Ohio predicts that this remarkable success will trigger a new batch of research. "That paper will give new directions for this type of research," he said. Sharon Lewin, a leading AIDS treatment researcher at the Doherty Institute of Infection and Immunity in Melbourne, Australia, said: This research work "has very convincing data" and it is "a very impressive Discovered.” But Lewin added a warning statement, which has been echoing in the hearts of many people, including the author of this study. She said: "We don't know whether this is a coincidence that happened on the monkey model," she said.

　　However, it is also possible that anti-α4ß7 is really effective, because this experimental design cannot reflect typical HIV infection. On the one hand, Ansari and Fauci's team started antiretroviral therapy 5 weeks after monkey infection, which is much earlier than most people start treatment. Louis Picker is an immunologist who developed an AIDS vaccine at Oregon Health and Science University in the United States. He was also curious whether the SIV virus used in this experiment may have been weakened, because his own experiment also used the same virus strain. Higher peak levels of virus were produced in the blood of untreated animals.

　　Picker suspected that some uncertain immune responses could explain the control of the virus in the monkey model. He said: "This experiment seems to be done to bring the host body close to a virus/immune balance, rather than simply controlling the virus level." He suspected that if you apply an antibody that acts on CD4 and then do the same experiment, you can see the same result.

　　But Picker admits that no other research team has published similar results. Perhaps more importantly, unlike the CD4 monoclonal antibody, anti-α4ß7 also exists in a form unique to humans and different from monkeys. A monoclonal antibody called vedolizumab has been approved for clinical use. In fact, three weeks ago, the National Institute of Allergy and Infectious Diseases in the United States has begun research in HIV-infected patients and hopes to enroll 20 patients. This experiment is mainly used for safety assessment. Participants will stop antiretroviral drug treatment, and researchers will closely monitor whether their HIV levels are elevated or are still suppressed. Fauci said: "We will soon find out whether these are nonsense or real and effective work."