Scientists never give up searching A complete cure for AIDS.
Writing| Ling JunSource | “Medical Community” Public Account< /span>On July 27 at the International AIDS Conference(AIDS 2022) in Montreal, Canada, scientists announced Two blockbuster cases are again driving AIDS “cure research”. In one case, a 66-year-old HIV-positive (HIV)infected persons may have been cured by stem cell transplantation. The unnamed patient has been living with HIV for more than 30 years and is the fourth person in the world to be declared cured of HIV. Currently, he has not received HIV antiretroviral therapy for 17 months, but there is still no sign of HIV replication in his body. 
The donor is a donor who was born with an “anti-HIV” gene called CCR5Δ32. CCR5 protein is a coreceptor for HIV to invade human immune cells. If it is compared to the “entrance”, when CCR5 has a specific mutation to become CCR5Δ32, the “entrance” is closed, and people may be immune to HIV for life. Stem cell transplantation is to seek out donors with CCR5Δ32 and transplant their stem cells into HIV-infected patients to rebuild the patient’s immune system and make them resistant to HIV. “It is equivalent to replacing the immune system of the “HIV-infected” with the immune system of the “naturally resistant to HIV.” Researchers at the City of Hope Medical Center say that AIDS will no longer pose a threat. However, studies have shown that only those who carry the homozygous CCR5Δ32 gene mutation can prevent the HIV virus from invading target cells, while the heterozygous CCR5-Δ32 gene mutation can only reduce and delay the disease progression. The former accounts for only about 1 percent of whites and almost zero elsewhere. “It is extremely difficult to find matching donors from the population, so we can try to use gene editing technology to transform first, and then carry out stem cell transplantation.” Professor Lu Hongzhou, President of Shenzhen Third People’s Hospital, told “Medical Medicine” Boundary” indicates. In September 2019, the New England Journal of Medicine reported that researchers used CRISPR/Cas 9 gene editing technology to knock out the CCR5 gene in donor hematopoietic stem cells, and then transplanted them into HIV-infected cells. In adult patients with acute lymphoblastic leukemia. “In the study, the in vitro knockout efficiency of CCR5 was low, only 17.8%. After the patient stopped antiretroviral drugs, the amount of HIV virus in the body also increased dramatically.” Professor Lu Hongzhou said to the “medical community” “Analysis, “However, since the gene-edited stem cells did not cause adverse effects on patients, and no gene mutation was found, it shows that this technology still has certain feasible prospects.”New cure CasesAIDS is no longer a terminal illness. In the late 1990s, with the advent of “highly active antiretroviral therapy”(HAART), or cocktail therapy, HIV-infected patients The virus level in the body can be effectively controlled, and it can even reach the “non-infectious” level on clinical indicators. However, the disadvantage is that the drug needs to be taken for life. In addition to the difference in compliance from person to person, there is also the hidden danger of long-term side effects, which creates the possibility for the emergence of drug-resistant viruses. As a result, scientists have never given up on finding a cure for AIDS. In 2007, the world’s first cured “Berlin patient” appeared, which caused a sensation in the academic world. Since then, “London patients”, “New York patients” and this time “City of Hope” patients have gradually entered the public eye. The commonality of the four infected persons is that they suffer from both AIDS and leukemia. To a certain extent, they are more like in the process of curing cancer, by the way to cure AIDS. In this treatment method, doctors must first destroy the patient’s original immune system with radiotherapy, chemotherapy and other means, kill a large number of HIV-infected immune cells, and then pass Stem cell transplantation to rebuild the immune system is a process full of risks, and may also require lifelong anti-rejection drugs after surgery. The current consensus in the academic community is that stem cell transplants would have been required if they were not suffering from lethal cancer, and it would be unethical to try this therapy on ordinary HIV-infected patients. “The first thing a transplant does is destroy your immune system, but you would never do that without cancer,” said Steven Deeks, an HIV specialist at the University of California, San Francisco, in an interview. . “Hematopoietic stem cell transplantation is a dangerous technique mainly used to treat leukemia. These HIV cured patients all suffer from malignant leukemia at the same time, so this method cannot be promoted on a large scale.” Lu Hongzhou The professor told the “medical community”. It is reported that “City of Hope” patients have been receivingRoutine HAART, until 2018 when he was diagnosed with acute myeloid leukemia, was allowed to try new treatments. It is also worth noting that the CCR5 protein is not the only receptor for HIV. If there are HIV strains that are addicted to the CXCR4 receptor, even implanting CCR5Δ32 may be ineffective. 15 years after drug withdrawal, no HIV viral load rebound has been foundin At the International AIDS Conference yesterday, scientists from the University of Barcelona in Spain also presented a report that a 59-year-old woman was considered to be in HIV remission, that is, to achieve a functional cure for HIV. In 2006, this woman participated in a clinical trial in Barcelona where she received antiviral therapy along with multiple immunomodulatory therapies, including an 8-week course of cyclosporine, to enhance immune cell control capacity of the HIV virus. After the trial, the woman stopped taking all related medications. Fifteen years later, no rebound in HIV viral load has been detected. But unlike “completely cured”, she still carries replicable HIV in her body. “It is unclear whether the immunomodulatory therapy the woman was using would work for other HIV-infected people,” a scientist involved in the study told ABC. “Why did the therapy work so well in her? All the other participants in the clinical trial failed,” he said. “Right now we’re trying to identify her genes, to see if there is a certain type, Help better relieve from HIV treatment, and whether it can be found in other people.”Professor Lu Hongzhou told the “medical community” that, unlike targeted drugs, immunomodulators have a broader spectrum of immunity The regulatory effect can play a comprehensive effect of enhancing the immune state or function of the host. “For immune checkpoint inhibition therapy, more emphasis is placed on precise genetic detection before treatment, and then the selection of immune checkpoints is optimized to achieve the best immune regulation effect.” “But the treatment method depends on the immune status of HIV-infected patients. The most important thing is that antiviral treatment is an indispensable prerequisite.” Professor Lu Hongzhou emphasized. Returning HIV-infected people to normal lifeWhether stem cell transplantation or immunomodulatory therapy, the ultimate goal of AIDS treatment research is to develop safe, Effective, but more importantly, “universal” therapies to help millions of people living with HIV around the world. On June 1, 2022, a study published in the top issue of “Nature” showed that after the combination of two broad-spectrum neutralizing monoclonal antibodies, the drug was stopped for up to 43 weeks , HIV virus levels in infected people are controlled and do not rebound. Researchers believe that in the future, HIV-infected patients may not need to take daily medication, but only need to administer monoclonal antibodies at a low frequency (such as once every two years). to return to normal life. There are also advances in the field of gene therapy. At the beginning of 2022, the US company Excision BioTherapeutics announced the initiation of a human phase 1/2 clinical trial of EBT-101, a therapy based on CRISPR gene editing technology, which completely smashes the HIV virus genome through “multiple cleavage”. “Including the Shock and Kill therapy proposed in recent years and various genetically engineered T cell transformation strategies are promising and promising directions for functional HIV cure,” said Professor Lu Hongzhou. In fact, in the presence of cost-effective HAART therapy, in addition to the limited increase in absolute health benefits, high prices, and difficulty in “mass production”, all further restrict the popularization of various cutting-edge therapies. Professor Lu Hongzhou believes that successful or good treatment cases provide a good idea for the follow-up research and the formulation of clinical treatment plans. To achieve a functional cure for the HIV-infected population, continuous scientific exploration and research are still needed. At present, this path has bright prospects, but it may not take a few years, but a few decades. “Existing HAART treatments cannot effectively address the problems of viral reservoirs, drug withdrawal rebound, and incomplete immune reconstitution. Therefore, even if there is a huge investment in other treatment strategies, it is a must for the academic community. “Professor Lu Hongzhou said. Want more hot features? Is one shot of the HPV vaccine enough? What is the difference between inactivated vaccines and mRNA vaccines? US FDA announces “1291 side effects of new crown vaccine”, is the truth? The “doctor” hand information you want to seeDoctor Station “Medical Feature” columns have