A new study of the effects of a new antibody treatment suggests it may offer a long-term solution for the control of HIV.
There is no doubt that antiretroviral therapy (ART) for HIV has transformed what used to be a death sentence into a chronic condition, allowing infected people to live decades longer.
But ART has its drawbacks, not only in terms of physical side effects such as decreased bone density and kidney problems, but also in that stopping treatment or just missing a few doses causes the virus to resurge.
The new study, published in the journal Science, concerns a different and potentially superior approach, in the form of a lasting immunotherapy that triggers an infected person's immune system to make antibodies against HIV and clear it from the body.
Dr. Till Schoofs, one of the study's first authors, and a researcher in molecular immunology at Rockefeller University in New York, NY, says:
"This study provides evidence that a single dose of an antibody stimulates patients' immune response, enabling them to make new or better antibodies against the virus."
Last year, the team reported that the same treatment, based on a molecule called 3BNC117, can greatly reduce the amount of virus present in a patient's blood.
Patients making new antibodies 6 months later
The new study reports the results of following the patients for a longer period of time to see how their immune systems are coping with the new therapy, explains Dr. Schoofs.
- More than 1.2 million Americans are infected with HIV
- Nearly one in eight are unaware they have HIV
- By race, HIV is more prevalent in black Americans.
3BNC117 is called a broadly neutralizing antibody because it can fight more than 80 percent of the over 200 strains of HIV that infect people around the world.
The molecule was isolated several years ago from a patient whose immune system showed exceptional ability in stopping the virus from infecting and killing CD4 immune cells, the destruction of which is a hallmark of AIDS.
For the phase I clinical trial, the researchers gave 15 patients with high blood levels of HIV a single injection of 3BNC117.
Then, 6 months later, 14 of the patients were making new antibodies that were able to neutralize a number of different strains of HIV.
Another group of untreated patients - whose HIV was controlled with ART - showed little change in their neutralizing activity over the same period, note the authors, who conclude that "3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1."
HIV-1 is the predominant strain of HIV that causes the vast majority of global HIV infections. When people talk about HIV, they usually mean HIV-1.
Dr. Schoofs suggests that since it usually takes years for the body to start making good antibodies against HIV, it could be that the effect of 3BNC117 increases with time, especially if the patient receives more than one dose.
Potential to clear latent HIV reservoirs
In another study published at the same time in the same journal, researchers investigate whether 3BNC117 offers further benefits compared with ART.
They put the trial results through a mathematical model and found that the drop in virus counts could not be explained just by 3BNC117 neutralizing HIV in the blood and stopping it infecting new cells.
Their analysis suggests something else is also going on, and further tests in mice revealed that the molecule appears to target already infected cells.
"This shows that the antibody not only can exert pressure on the virus, but also can shorten the survival of infected cells."
First author Ching-Lan Lu
The researchers suggest 3BNC117 therapy could address a major obstacle in treating HIV, how to clear the latent reservoir that allows the virus to hide out in the body and evade treatment.
The researchers now plan to test the molecule with other anti-HIV antibodies to see if it can produce an even stronger antiviral effect. They are also going to carry out a phase II trial involving patients switching from ART to the new therapy.