Original Lingjun medical field
The study once again suggests that monoclonal antibody combined therapy is one of the most promising methods to completely cure AIDS.
Author | Ling Jun
Source | "Medical" WeChat official account
On June 1, 2022, the top magazine Nature published a heavy research on AIDS treatment.
In the experiment, as an alternative therapy to conventional antiretroviral therapy (ART), the HIV level in the infected person was controlled for up to 43 weeks after the combination of two broad-spectrum neutralizing monoclonal antibodies.
Researchers believe that in the future, HIV-infected people may not need ART treatment every day, but only need low-frequency (such as biennial) medication, and perhaps combined with long-acting antiretroviral drugs, they can return to normal life.
Based on this research, Professor Lu Hongzhou, Dean of the Third People’s Hospital of Shenzhen, told the "medical field" that monoclonal antibody combination therapy is one of the most promising methods to completely cure AIDS. "At present, many studies have shown that low-frequency use of monoclonal antibody combination therapy can effectively maintain virus inhibition, but the virus will rebound after stopping drug use. It is expected to change this situation by further screening and developing long-acting monoclonal antibodies."
High level of HIV inhibition
Up to 43 weeks
Today, 40 years later, AIDS is no longer a "terminal disease".
With the advent of "highly effective antiretroviral therapy" (HAART), that is, cocktail therapy, the virus level in HIV-infected people has been effectively controlled, even reaching "non-infectious" in clinical indicators, and the life expectancy is close to that of ordinary people.
But the defects are also obvious. HIV-infected people need to take medicine every day and for life, and their compliance varies from person to person. Once the drug is stopped, the virus level in the body will rebound quickly. In addition, lifelong use of drugs may have long-term side effects and create the possibility for the emergence of drug-resistant viruses.
This time, the researchers conducted a small phase I clinical trial, and tested the combination therapy of two monoclonal antibodies, 3BNC117 and 10-1074, which are aimed at different targets, and are expected to bring a breakthrough in "long-term treatment".
The trial is divided into two parts. The first is a randomized, double-blind, placebo-controlled study involving 14 infected people. They first received antiretroviral therapy (ART), then stopped taking drugs and received up to eight times of "monoclonal antibody combination therapy" or placebo-twice in the first month and once a month thereafter.
The results showed that, except one infected person who secretly recovered ART for fear of illness, the HIV levels of the other six placebo subjects all rebounded 28 weeks ago, and ART treatment must be restarted immediately, with a median time of 9.4 weeks.
All 7 people in the monoclonal antibody combined treatment group did not need to restart ART. Five of them showed a very high level of HIV viremia inhibition, and the effect lasted for up to 43 weeks, that is, 19 weeks after stopping the "monoclonal antibody combination therapy".
However, it is worth noting that in the second part of the experiment, the researchers recruited another five HIV-infected people who had not received ART. After the start of "monoclonal antibody combined therapy", only two people achieved complete inhibition of HIV, and the average duration was 41.7 weeks.
Further research found that the other three infected people whose virus levels were not controlled were resistant to two kinds of monoclonal antibodies.
The same findings also appeared in the first trial. Although there was no need to restart ART treatment in the treatment group, two people had a partial rebound in virus level in the first 8 weeks, which was also due to the existence of drug-resistant viruses in the body.
The researchers pointed out, "This suggests that the premise of treatment is that there can be no virus resistant to the corresponding monoclonal antibody in the infected person before administration.
Can we finally realize the "clinical cure" of AIDS?
This is not the first time to study the treatment of AIDS with 3BNC117 and 10-1074.
As early as 2018, the team of Professor Nussenzweig from Rockefeller University published a paper in Nature: After stopping ART, using this monoclonal antibody combination can effectively inhibit HIV for 15-30 weeks (median 21 weeks).
"They can inhibit HIV in infected people for several months, and may produce new methods to prevent and treat AIDS." In 2020, Rockefeller University published a document in official website, and the antibody combination has been acquired by a large multinational pharmaceutical company in the United States.
On April 13th, 2022, Professor Nussenzweig and his team updated the research progress again. All the infected people who received the combination therapy of the monoclonal antibody for 7 times still maintained virus inhibition within 21 to 48 weeks after stopping the injection.
Professor Lu Hongzhou told the medical community that monoclonal antibody therapy has been widely studied and applied in the field of HIV prevention and treatment in recent years, and it has been proved that it can inhibit HIV-1 infection in animal models for several years.
"The breakthrough significance of the latest research is that it is further confirmed that the combination therapy of broad-spectrum neutralizing monoclonal antibody can inhibit the virus level in human body for a long time, and it shows good safety and tolerance, which is expected to become an alternative to daily ART." Professor Lu Hongzhou said.
However, combined with the latest research, Professor Lu Hongzhou said that there are still some problems to be solved urgently.
First of all, the combination therapy of monoclonal antibodies needs to screen HIV drug resistance in the infected person in advance, and the sensitivity test for monoclonal antibodies requires high test technology itself, which may limit the popularization and application of this therapy.
"HIV virus has a high frequency of mutation and a variety of immune escape strategies, and the problem of drug resistance can not be ignored. Therefore, it is also the key to develop effective extended-spectrum neutralizing antibodies and jointly identify monoclonal antibodies against different targets of the virus in the future." Professor Lu Hongzhou said.
Secondly, the study mentioned that although it is expected to greatly reduce the frequency of drug use (only twice a year), in the current course of 8 doses, once the drug is completely stopped, the virus level will eventually rebound.
"Whether the infection process can be completely changed, that is, whether the virus can be suppressed for a long time after stopping the drug, needs to be finally solved and evaluated by increasing the previous course of treatment and extending the follow-up time." The researchers said.
Professor Lu Hongzhou believes that whether "long-acting monoclonal antibody combination" can help HIV-infected people to suppress the virus in their bodies for a long time (such as several years) and achieve the final "clinical cure" by clearing the HIV virus repository still needs longer-term clinical data to support.
Source: medical profession
Editor: Song Kunlun
Proofreading: Zang Hengjia
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