Antiretroviral therapy (ART) is the gold standard for HIV treatment. But patients need to take their medicines every day or risk a rapid virus rebound. That makes the drugs hard to adhere to in a lifelong battle. Scientists at Rockefeller University now suggest that combining HIV antibodies could keep the virus in check for months, potentially relieving patients of their daily pill-taking routine.
In a small phase 1b trial, the researchers combined two broadly neutralizing antibodies (bNAbs), dubbed 3BNC117 and 10-1074. These antibodies were found in "elite controllers," or people whose bodies successfully fight off HIV without the help of drugs. They work by targeting proteins on HIV’s surface so that the body’s immune system can seek out and destroy the virus.
Participants whose viral load had already been controlled stopped taking their antiretroviral drugs and received three infusions of the bNAbs three weeks apart.
Among nine individuals who had viruses that were sensitive to both antibodies, the treatment suppressed their viral load for a median of 21 weeks—or 15 weeks after their last injection. Two of them maintained virologic control at the 30-week follow-up. The team reported the results in the journal Nature.
In a separate study, seven patients who hadn’t received ART and had viruses still circulating in their bloodstream were treated with bNAbs and maintained significant viral reduction for up to three months, according to results published in Nature Medicine.
The new findings from the Rockefeller researchers were encouraging, because previous studies using a single bNAb only reduced the levels of virus for a short time. By contrast, 3BNC117 and 10-1074 attack HIV from two different angles, so administering them together might reduce the likelihood of resistance, the researchers believe.
The two antibodies offer other advantages, too. "The expectation is that these new variants will have three- to four-fold longer half-lives," said Rockefeller’s Michel Nussenzweig, a co-leader in both bNAb studies, in a statement. "So we may be able to give the antibodies once or twice a year."
Moreover, Nussenzweig said that bNAb therapy could help the body produce HIV-fighting antibodies on its own, much like anti-cancer antibody therapies that boost the natural immune system.
Other efforts are underway in the HIV community to develop safe therapies that require less frequent dosing. A partnership between GlaxoSmithKline’s HIV unit ViiV Healthcare and Johnson & Johnson’s Janssen has demonstrated in a phase 3 trial that a combination of cabotegravir and rilpivirine could be a monthly ART, and the two companies are also testing the regimen as a bi-monthly injectable.
Of course, the once-and-for-all approach would be to clear "reservoirs" where HIV hides from ARTs and bide its time to bounce back. Scientists at the University of North Carolina at Chapel Hill recently showed that a T-cell therapy was well tolerated in a small group of patients, teeing up further studies that combine it with latency-reversing drugs.
According to the Rockefeller researchers, bNAbs also hold the potential to prevent HIV. Gilead Sciences’ Truvada is approved for pre-exposure prophylaxis (PrEP) but requires daily administration. A team from the International AIDS Vaccine Initiative and the Scripps Research Institute recently identified potent bnAbs that could block most HIV strains by targeting a "site of vulnerability."
Promising as they are, bNAb treatments do have their limitations. HIV virus has many variants and is prone to mutation especially when it’s not properly suppressed. In some patients, antibodies are unable target all of them. In the Nature study, for example, two participants who experienced viral rebound at 12 weeks were found to host HIV variants that were resistant to at least one bNAb.
"These two antibodies are not going to work for everyone," said the studies’ co-leader, Marina Caskey, in a statement. "But if we start to combine this therapy with other antibodies or with antiretroviral drugs, it could be effective in more people—and that's something we hope to look at in future studies."
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