Clue to HIV Cure: Antibodies ‘Train’ the Immune System for Long-Term Control

A finding has emerged that could increase the possibility of an HIV (human immunodeficiency virus) cure. A study found that broadly neutralizing antibodies “train” patients’ own immune systems to control the virus over the long term.

According to Azur Life Science on the 18th (local time), results from the RIO clinical trial, conducted jointly by Rockefeller University in the United States, Imperial College London and the University of Oxford in the United Kingdom, were published in the international journal Nature Medicine.

The researchers conducted the trial in 68 men with HIV, administering two long-acting broadly neutralizing antibodies (bNAbs) or a placebo, then interrupting antiretroviral therapy (ART).

Initial results showed that a single dose was enough for most participants to maintain undetectable virus levels for up to 20 weeks without ART. Among participants who maintained suppression, half remained undetectable for 48 weeks and one-third for 72 weeks.

Of the 29 participants who received antibodies, 38% showed a pattern of “viral blips,” in which the virus repeatedly fluctuated at low levels. This pattern lasted for up to 58 weeks.

Michel Nussenzweig, head of the Laboratory of Molecular Immunology at Rockefeller University, said, “It looks as if the antibodies teach the immune system how to control HIV,” adding, “The participants’ own immune activity acts as a second component of the antibodies.”

Laboratory analyses showed that after antibody treatment, the half-life of intact proviruses fell to about 36 weeks. During ART, it took 4–7 years.

The most notable finding was that participants who achieved long-term control were more likely to have their own neutralizing antibodies. Participants with these antibodies remained off ART for an average of 108 weeks before restarting, compared with just 27.5 weeks for those without them.

Nussenzweig compared the system to a tricycle. If the two administered antibodies are the two wheels, the patient’s own antibodies act as a third wheel that provides balance.

“It was surprising that the patients’ own immune systems maintained the balance,” he said, “because it had long been clear that their own antibody responses alone could not control anything.”

The researchers said the findings also point to a way to improve bNAb treatment: vaccinating patients to train them to produce their own antibodies, then administering therapeutic antibodies.

“The problem with this treatment is that not everyone responds,” Nussenzweig said. “We’re looking for ways to make good outcomes more common, and this study has provided a clue.”