ART is a GREAT VICTORY. BUT WE NEED MORE EFFICIENT THERAPIES AND BETTER QUALITY OF LIFE
The development of antiretroviral therapy, a combination of drugs that prevents the replication of HIV in the body, has transformed the treatment of this infection. What was once a death sentence, is now a chronic condition that people can live with for decades.
But this therapy has disadvantages. There are side effects, including kidney problems, decreased bone density and gastrointestinal problems. And if a person interrupts their treatment, even if there are a few doses left, the level of virus in the body is able to return quickly.
Researchers at Rockefeller University, along with colleagues at the University of Cologne, are developing a new type of antibody-based treatment that can provide a better long-term strategy for HIV control.
Recent findings from an 1 phase clinical trial, published in 5 in May Science; offer new insights into how antibody functions.
"This study provides evidence that a single dose of an antibody stimulates an immune response in patients' allowing them to make new or better antibodies against the virus," explains Schoofs, a postdoctoral fellow and one of the first authors of the study. Schoofs is a member of the Laboratory of Molecular Immunology, led by Michel Nussenzweig, Zanvil A. Cohn and Ralph M. Steinman Professor, who is the senior author of the study.
"We reported last year that this treatment can significantly reduce the amount of virus that is present in someone's blood," Dr. Schoofs adds, "but we wanted to follow patients over a long period of time to study how their immune systems, behaved adapting to the new therapy. "
The neutralization of a deadly virus
The tests with aa molecule 3BNC117 were conducted at University Hospital RockefellerA molecule 3BNC117
The molecule used in the research, 3BNC117, is called as a broadly neutralizing antibody because it has the ability to fight against a wide range of HIV strains. Johannes Scheid, a student in the laboratory Nussenzweig, has been isolating this molecule for several years from an HIV-infected patient whose immune system had an exceptional ability to neutralize HIV in the blood by preventing the virus from infecting and destroying a specific type of immune cells called CD4 cells. immune response in patients with HIV. The destruction of CD4 cells is a hallmark of AIDS.
Early studies have shown that 3BNC117 can neutralize more than 80 percent of HIV strains that are found across the globe. The researchers therefore hypothesized that introducing this antibody (3BNC117) into patients to help fight the virus better.
The clinical trial included 15 patients who had elevated viral loads and another twelve patients whose virus levels were being monitored with antiretroviral therapy (ART). Most participants in the trials were treated at Rockefeller University Hospital. Patients received a single infusion with one dose of the molecule 3BNC117 (which is the antibody) and accompany these patients outpatient for a period of six months.
New antibodies equal to those that were infused were created by the organism that received them
The researchers found that 14 of 15 patients who had high levels of virus at the time they received the antibody were able to create new antibodies equal to those infused at baseline and to make new antibodies that were able to neutralize a number of different strains of HIV.
"It usually takes several years for the body to start making good antibodies against HIV," says Schoofs. "Therefore, there may still be a better effect later on, especially if the patient has received more than one dose of 3BNC117 (the antibody)."
The next steps in this research to test antibody 3BNC117 in combination with other antibodies that also demonstrate HIV attack specificity to determine whether it is possible to generate an even stronger antiretroviral response can be generated. The researchers will also conduct a 2 phase study with patients receiving antiretroviral therapy who will be switched to treatment with the antibodies.
Exploring the function of an antibody
In the companion study, (I followed the link and the matter is paid and dear. Can not afford it ... I'm very sorry) published that dealt with the same aspect in the journal, the researchers wanted to be able to find a way to determine what new and possible benefits of treatment with 3BNC117 might have on antiretroviral therapy.
They examined the results of the clinical trial and used a mathematical model of HIV dynamics to predict how the patient would reduce HIV levels in the blood with 3BNC117 that did nothing more than neutralize HIV in the blood and block new infections . Their analysis showed that neutralizing the virus alone did not explain the sudden drop in virus levels observed in patients, prompting scientists to suspect there must be another component to the effectiveness of the antibody.
Working on a mouse model, researchers saw evidence that 3BNC117 was able to trigger immune cells and accelerate the fight against HIV-infected cells.
"This shows that the antibody can not only exert pressure on the virus but can also shorten the survival of infected cells," says first author Ching-Lan Lu, on a student's visit to Dr. Nussenzweig's laboratory. "Our results explain why post-exposure prophylaxis" short-term treatment after exposure to HIV to reduce infection "with antibodies is more effective than ART in our models with guinea pigs."
They concluded that, in addition, there is potential property could make it possible to address a major obstacle to curing the HIV virus: stopping the ability of HIV to establish a latent reservoir soon after infection and thus hiding in the body and escaping from the treatments. A follow-up clinical study is currently underway at Rockefeller to assess whether the supply of drugs with antibodies to patients receiving antiretroviral therapy may help reduce the withdrawal of HIV from their reservoirs or alter these reservoirs of HIV.
6 May 2016
Translated by Original Claudio Souza in Antibody therapy opens the door to new treatment of HIV potential reviewed by Mara Macedo in 13 May 2016
More information: T. Schoofs et al, HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1, Science (2016). DOI: 10.1126 / science.aaf0972
C.-L. Lu et al. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo, Science (2016). DOI: 10.1126 / science.aaf1279
Reference Officer: Science
Provided by: Rockefeller University