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Nine of 11 people living with HIV maintained a "beautiful and long-lasting" viral suppression after receiving two highly neutralizing antibodies (BNAbs) against HIV, almost tripling the average viral rebound observed in single BNAb studies.
"This research confirms what we all thought we knew: we need a combination antibody therapy to suppress HIV," said Trevor Crowell, MD, Ph.D., of the Johns Hopkins School of Medicine in Baltimore. and the US military program. l & # 39; study.
"We learned this lesson with ART and are now seeing it with an immune intervention for HIV treatment," he said. Medscape Medical News.
This could mean that the future of remission without treatment will be more similar to current antiretroviral therapy than a single injection that indefinitely removes HIV.
The combination of bNAb has been described in two recent publications (Nature. 2018; 561: 479-484 and Nat Med. Posted online September 26, 2018).
Coevolution of HIV B cells
When a person gets HIV, the immune system is usually silent. But he wakes up with time and starts to launch an attack against the virus. This attack, announced by B cells, is in the form of antibodies designed to block or stop different stages of HIV infection.
The problem is that, just as an antibody starts to gain a foothold, the virus is transformed, eliminating the stain on its sweet outer shell where the antibody acts. B cells try another antibody, and another, trying each time to stop HIV and each time to work a little before the virus evolves to escape the system.
The bad news is that the immune system is rarely noticed. The good news, though, is that scientists have examined these B cells to identify antibodies that are both potent and work on various HIV viruses.
This is how researchers at the Rockefeller University of New York, who examined hundreds of anti-HIV envelopes, found 3BNC117 and 10-1074, two antibodies that target two different points on these envelopes.
Both antibodies were studied individually and each time they suppressed the virus, at least in some patients. But every time the virus has rebounded, as it has done in previous monotherapy studies, it has sometimes developed resistance to this antibody.
"It sounds like what happened when simple antiretroviral drugs were administered several years ago," said investigator Marina Caskey, MD. "Thus, it was not necessarily surprising that patients treated with combined antibodies maintain successful viral suppression similar to that achieved with antiretroviral therapy."
What surprised him, says Caskey, is how long we have been able to maintain the repression.
Triple the time and always go
An earlier study demonstrated that HIV was suppressed for 10 weeks without antiretroviral therapy in patients who received 3BNC117 alone (Nature. 2016: 535: 566-560). And in patients with detectable viral load who received 10 to 1074 unattached individuals, the mean half-life was 12.8 days (Nat Med. 2017 23: 185-191). The administration of VRC01, another widely studied antibody, suppressed HIV for approximately 5.6 weeks (N Engl J Med. 2016 375; 2037-2050).
For the combination of 3BNC117 plus 10-1074, administered three times in 6 weeks, the mean viral rebound time was 21 weeks. "It's been 4 months since the last dose of antibodies," Caskey said.
But that's not all. As with all antibody studies, different people have reacted to antibodies in different ways. Two people bounced back – one to five weeks and one to seven weeks – and later proved to be resistant to one or the other of the antibodies.
"There seems to be a higher bar at 3BNC117 resistance than at a resistance of 10-1074," Caskey said. "What we saw in this study was that for the people who responded, the virus did not manifest until 3BNC117 was eliminated."
Determining who is subject to resistance to these antibodies could lead to more effective treatment. "This is one of the most difficult areas to solve," she said.
A "glimmer of hope"
When the study ended at 30 weeks, two of the 11 participants were again removed virally. These are the ones that "give an idea of how HIV remission really is possible," said Crowell.
Participants chose to stay out of treatment and the team continues to follow them.
What made these two people allow them to stay virally blocked? Caskey explained that this could be a combination of the person's particular virus, the specificities of that person's immune system and how the antibody's administration itself modifies the way the immune system sees the virus.
"We are at the beginning of understanding that," she added. When these antibodies bind to the virus, "they mark and signal to the rest of the immune system that it is something that it must eliminate, so even if it is not a vaccine in itself, it can have a vaccine effect ".
So even if it's not a vaccine in itself, it can have a vaccine effect.
But that does not mean that everyone should miss and start asking for the 4-month treatment for HIV. Much remains to be done, Caskey said.
Much larger studies with more diverse populations (only one woman was involved in the trial) are needed to determine whether the results were participant-specific or more generalizable. And a test is needed to identify people at risk of resistance before administering LABAs.
In fact, Caskey and his colleagues are conducting larger studies, which are currently in the registration phase.
This is not a cure, she said. But this is also not the end of the development of combined therapy by bNAb, said Anthony Fauci, MD, of the National Institutes of Allergy and Infectious Diseases.
"These are standard antibodies, and they suppressed the virus for a median of 21 weeks," said Fauci. "If you use the same proof of principle and long-acting antibodies, it means that it's possible that you can give an antibody twice a year, nothing else, and continue to remove the virus. "
This study was funded by the Bill and Melinda Gates Foundation, the European Research Council, the German Center for infection research, the DFG Heisenberg program and the National Institutes of Health. Crowell, Caskey and Fauci did not reveal any relevant financial relationship.
Follow Medscape on Twitter @Medscape and Heather Boerner @Ankle
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