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Produced by | Huxiu Technology Medical Group

Author | Chen Guangjing

Editor | Miao Zhengqing

Header image | Visual China

Have humans found a cure for AIDS?

On July 20, the news that "the world's seventh AIDS patient may be cured" topped the hot search list on multiple social platforms.

According to reports from many well-known domestic and foreign media, a 60-year-old German man has not had any symptoms or detected any surviving HIV since receiving a stem cell transplant in 2015. He may be the seventh AIDS patient in the world to be "cured" after receiving a stem cell transplant.It has been nearly 10 years since the transplant and about 6 years since I stopped antiviral treatment.

Researcher Dr. Christian Gaeble still publicly stated that the longer the patients are in remission, the more confident they are. "We may have really eradicated all HIV."

A domestic infectious disease expert has also publicly stated that seven patients have been "cured" using this method, which also shows the feasibility of this method. He believes that on this basis, researchers are expected to use related principles to explore safer treatment options.

As we can see, recently, good news has been frequently reported in the field of curing and preventing AIDS. Even the "cure" of AIDS by stem cell transplantation, which is involved in this hot event, is not new - since 2007, this therapy has created six such miracles in Berlin, London, New York, City of Hope, Düsseldorf, and Geneva.

Behind these good news that have made the public and capital unable to help but celebrate, a true cure for AIDS seems to be on the verge of being revealed.

The greatest significance may be to reveal the code of "healing"

Although the emergence of the world's seventh AIDS cured patient has caused quite a stir in China, virology experts do not believe that stem cell transplantation therapy can truly conquer AIDS.

"The greatest significance of this type of case is to discover the underlying principles by studying related cases.。”Virology expert Chang Rongshan told Huxiu that, judging from the current situation, the stem cell transplantation therapy, which has been successful seven times, is of little significance in itself and cannot be used as a widely promoted AIDS treatment method.

According to more public information, like five of the six previously "cured" patients, the 60-year-old German male patient also received a bone marrow transplant containingCCR5 gene mutationResearchers believe that people who carry this gene mutation are naturally resistant to HIV, and their stem cells entering the patient's body will also make it difficult for HIV to enter the latter's somatic cells.

More studies believe that CCR5 is the main auxiliary receptor used by HIV, which is responsible for viral transmission and is mainly expressed in memory T cells, macrophages and immature dendritic cells (which can be understood as encoding and generating a certain protein - Tiger Sniff Note).

If the human body has a specific CCR5 mutation, such as the CCR5△32 gene mutation, the T cells will be defective and can only encode an incompetent truncated protein that cannot be transported to the cell surface, and cannot assist the HIV virus to enter the T cells, and corresponding infection and viral replication cannot proceed.

The patients who were “cured” above received transplants of stem cells carrying the relevant defects, which actually reshaped their immune systems. This is the basic logic of their cure.

Now, CCR5 has also become a therapeutic target for various inflammatory diseases such as anti-AIDS drugs.

Timothy Ray Brown, known as the "Berlin Patient", set up a foundation to promote AIDS treatment research.

From: Visual China

However, there is still much room for further research regarding bone marrow transplantation therapy and CCR5.

For example, not every transplant of stem cells containing a CCR5 gene mutation has a good outcome. According to an article by an expert from the Chinese Center for Disease Control and Prevention, the early cured patients, the "Berlin patient" and the "London patient," both had graft-versus-host disease, and even had multiple infections and weight loss. The "New York patient" was discharged quickly without any obvious complications.

Does this individual difference mean that patients with certain characteristics are more suitable for this type of treatment?

Another example: The stem cells received by the fifth "cured" patient did not contain the CCR5 gene mutation. Does this mean that the CCR5 mutation is not necessary? The mechanism of "curing" is still unclear.

"These all need further research," Chang Rongshan pointed out to Huxiu.

In addition, even if the CCR5 gene mutation is indeed helpful for cure, too few stem cell donors is also a big problem. According to the article by the experts of the Chinese Center for Disease Control and Prevention, there are only about 3‰ people with CCR5Δ32 gene mutation in China, and they are mainly ethnic minorities, with almost no Han people; in Europe, the average mutation rate is about 10%.

Moreover, the success rate of current antiviral "cocktail" therapy is already relatively high, and few patients are willing to take the risk of undergoing stem cell transplantation for the purpose of cure.

Based on the above reasons, in fact, although professionals highly recognize the significance of their research, they still have doubts about the prospects of cell transplantation therapy.

Who is the real potential for "cure"?

"In the next 5 to 10 years, it is expected that there will be a functional cure for AIDS," Chang Rongshan told Huxiu.

Data shows that the global AIDS drug market will reach about 46 billion US dollars by 2028. In this market, curative drugs have an absolute competitive advantage. In order to achieve this goal, research institutions and enterprises are very enthusiastic about development.

In addition to the aforementioned CCR5 targets, other hot research and development targets include Gilead's capsid inhibitors, which were previously very popular, and research on "elite controllers".——It is estimated that among 300 to 500 HIV-infected people, there is one person with a very low viral load. The virus cannot be detected in multiple tests within half a year, or the virus cannot be detected in 90% of tests for more than 10 years. This type of "chosen one" also has multiple mutations, which is of great inspiration for the development of new drugs.Specific therapies also cover multiple fields such as immunotherapy and gene therapy.

Stem cell transplantation from xenogeneic donors has been successful in treating leukemia, but the indications for cure are still extremely limited.Chang Rongshan believes that the genetically modified "T cell vaccine" is the most promising therapy.He believes that in-depth research on the possible "mechanism" behind this seventh AIDS cure patient in the world will promote the successful launch of "therapeutic T cell vaccines" in the future.

If further research can confirm the role of CCR5, and/or superimpose the role of unknown gene products, it will be possible to create a universal T cell vaccine with therapeutic effects in vitro through gene editing and then return it to the patient, similar to CAR-T therapy. The industry calls it a therapeutic T cell vaccine.

In addition to AIDS, it can also cure many diseases caused by viral infections with extensive immunosuppression, such as AIDS, hepatitis B, human papillomavirus, herpes zoster, human herpes virus type 2, and other refractory chronic infectious diseases.“Compared to cancer, these diseases have a much larger patient population and represent the largest unmet medical need.demand." Chang Rongshan told Huxiu.

In fact, in May this year, Chinese researchers published relevant research results in the authoritative journal Cell Discovery.

According to the research results, CAR-T cells developed by Xu Jianqing, Zhang Xiaoyan, Zhang Renfang from Shanghai Public Health Clinical Center of Fudan University, Sun Yongtao from Tangdu Hospital of Fourth Military Medical University, and Leng Jing from Guangxi University of Chinese Medicine have been successfully used in Phase 1 clinical trials.Clinical TrialsIn the study, the peak HIV titer of the subjects was reduced by 74.3%, and the viral load was reduced by an average of 67.1%. This result shows the potential of this therapy.

Earlier, a research team from the University of California, Los Angeles, also achieved lasting results in using CAR-T to fight HIV.

Generally speaking, the cure for AIDS can be divided into two types.One is to completely eliminate the virus, which is called "eradication cure". The other is the so-called "functional cure", which means that after treatment, without the need for continued antiviral drug treatment, the patient's viral load level is so low that it cannot be detected, and there are no symptoms related to HIV infection and no risk of HIV transmission.

HIV infection is a chronic infection. The virus can integrate its own genetic material into human cells, and its main target of attack is also human immune cells.After infection, once the incubation period has passed, these HIV genes integrated into human cells are almost impossible to eliminate. According to the current level of biological research, it is extremely difficult to completely eliminate these viruses.Hepatitis B also has this characteristic. For these two chronic infections, there is no hope for eradication of the disease, but there is still hope for a functional cure.

As mentioned earlier, Chang Rongshan optimistically estimates that there will likely be a breakthrough in the field of functional cure for AIDS in five years, which will also benefit other chronic infectious diseases.

From: Visual China

According to data from the United Nations AIDS Program in 2023, there are 39 million people living with HIV worldwide, of which 29.8 million are receiving antiretroviral treatment. In the previous year, there were 1.3 million new HIV infections and 630,000 deaths from AIDS-related diseases worldwide.

Behind these infected people, there are a large number of family members who are worried about infection and live in panic. How to ensure that they can live a normal life is also a problem that requires time, energy and money to properly solve.

It can be said that AIDS remains one of the world's most serious public health challenges.

Similarly, there are many infectious diseases that need treatment worldwide. Among them, there are about 296 million people with chronic hepatitis B virus infection alone, and nearly 900,000 people die each year from diseases such as cirrhosis and liver cancer caused by hepatitis B virus infection. Eliminating these diseases is also an urgent goal for all mankind. The experience of curing AIDS is also of reference significance for the treatment of such diseases.

Today, AIDS has gone from being a deadly disease to being preventable and treatable. Drugs are also being continuously updated, with side effects gradually decreasing, and becoming more and more suitable for lifelong use. Despite this, we still cannot relax our vigilance against HIV and take it lightly.Whether there is a cure or not, prevention is always the best weapon.