If the past four decades have taught us anything about HIV, it's to adjust our expectations-despite enormous progress in controlling the virus, no treatment can yet completely eradicate HIV once it has taken hold. But promising results from a recent clinical trial suggest that broadly neutralizing antibody therapy (bNAbs) may be able to accomplish the next best thing.
Data from the trial-a collaboration led by Rockefeller, Imperial College London and the University of Oxford (RIO)-was recently presented at the Conference on Retroviruses and Opportunistic Infections. The results suggest that most participants who received a treatment of two bNAbs just once, in lieu of daily antiretroviral therapy, were able to keep the virus at undetectable levels for up to 20 weeks. Participants who maintained suppression were given the option to receive a second dose of the bNAbs at 20 weeks or later.
As the researchers continued to follow the participants, this latter group showed even more promise. At 48 weeks, half of the participants were still undetectable, and one third remained so even at 72 weeks-roughly a year after their last treatment. The results suggest that, where an HIV cure may not be possible, something equivalent to remission or treatment-free long-term control may be within reach.
"Current antiretroviral therapy is unable to target the so-called 'reservoir' of HIV infection-which is why there is no cure," says Michel Nussenzweig, Rockefeller's Zanvil A. Cohn and Ralph M. Steinman Professor and a co-principal investigator. "Our trial has shown, for the first time, that long-acting bNAbs significantly reduced the size of this reservoir, even reaching undetectable levels in some participants." adds Marina Caskey, professor of clinical investigation at Rockefeller.
Currently, individuals living with HIV must take a daily antiretroviral pill to maintain an undetectable viral load. When therapy is stopped, the virus quickly ramps back up. The RIO trial, led by Sarah Fidler of Imperial College, John Frater of the University of Oxford, Nussenzweig and Caskey, is the latest advance toward what might be termed HIV remission-not quite a cure, but a state that keeps patients healthy for a long time without medication. This trial stands on the shoulders of prior work from Caskey and Nussenzweig, published in Nature in 2022, which demonstrated that bNAbs administered to 18 patients over five months yielded prolonged viral suppression.
The RIO trial, funded by the Gates Foundation and Rockefeller's Stavros Niarchos Institute of Infectious Diseases, randomized 68 participants to receive either bNAbs or a placebo. They then stopped taking their daily pills. Regular follow-up allowed the researchers to test each participant's viral load and, 20 weeks later, individuals who had received bNAbs were 91 percent less likely to have experienced viral rebound than those who had received the placebo. At 72 weeks-a year or nearly a year and a half from receiving their last treatment-one in three participants were still undetectable.
"This is the first time a long-acting immune-based therapy has shown sustained viral control in multiple participants, allowing them to discontinue daily medication for over a year," Fidler says.
The study remains ongoing. Caskey and Nussenzweig suggest that a cure may now be back on the table. Work from their lab demonstrates that the bNAbs in the RIO trial directly reduced the elusive HIV reservoir. "Since eliminating the reservoir is crucial for curing HIV, these findings represent a significant step forward," Nussenzweig says.
