The New York Times, August 8, 2024
Scientists have developed a new weapon against H.I.V.: a molecular mimic that invades a cell and steals essential proteins from the virus.
A study published in Science on Thursday reported that this viral thief prevented H.I.V. from multiplying inside of monkeys.
The new therapeutic approach will soon be tested in people, the scientists said. Four or five volunteers with H.I.V. will receive a single injection of the engineered virus. “This is imminent,” said Leor Weinberger, a virologist at the University of California, San Francisco, who led the new study.
In a normal H.I.V. infection, the virus slips into an immune cell and hijacks its host’s DNA to make copies of itself, which then burst out of the cell. After a large number of cells have been infected, the immune system collapses, causing AIDS.
For decades, scientists have developed drugs for H.I.V. that attack the virus itself. Some drugs, for example, prevent a protein called a protease from activating H.I.V. And a drug called lenacapavir blocks the proteins that form the virus’s shell. Last week, researchers reported that they could keep the virus at low levels by injecting lenacapavir into volunteers once every six months.
Twenty years ago, Dr. Weinberger set out to try an entirely different approach: creating an impostor virus that interfered with H.I.V.’s normal life cycle.
“I was worried that people would just dismiss me as a wacko, which was not completely unwarranted,” Dr. Weinberger recalled.
Over years, Dr. Weinberger and his colleagues created what they now call therapeutic interfering particles, or TIPs, which have about half of the genetic material of normal H.I.V.
Dr. Weinberger and his colleagues discovered that their TIPs could infect human immune cells in a petri dish and insert their genes into DNA. But they couldn’t get the cells to produce new viruses.
If H.I.V. particles were added to a TIP-infected cell, however, TIP could replicate. The cell also made protein shells — some filled with H.I.V. genes, and others filled with TIP genes.
Dr. Weinberger and his colleagues engineered the TIPs to do a better job of entering the shells. When the infected cells burst open, they released three times more TIPs than H.I.V. viruses.
The researchers predicted that this advantage should allow TIPs to quickly reduce H.I.V. to very low levels. To test their hypothesis, they ran an experiment on monkeys.
The scientists infected the monkeys with a primate version of H.I.V. that normally kills the animals in a matter of weeks. They then gave the animals a single injection of TIPs.
As they predicted, the treatment drove down the level of the virus by a factor of 10,000. Almost all of the monkeys that received the TIPs survived, showing no sign of AIDS. “They looked healthy in any way we could check,” Dr. Weinberger said.
Based on these promising results, Dr. Weinberger and his colleagues have been moving toward testing the experimental treatment in people. They have recruited volunteers infected with H.I.V. who are also terminally ill with cancer and other diseases.
They plan to give the volunteers a single injection of TIPs. If the volunteers fare well, Dr. Weinberg’s team will expand the trial to H.I.V.-infected volunteers who are not terminally ill. They predict that TIPs will drive down their H.I.V. count, as it did in monkeys, he said.
Dr. Weinberger hopes that if TIPs make it through clinical trials, they can be used to offer more protection against AIDS in poor countries. Daily doses of protease inhibitors are too expensive for most people with H.I.V. to rely on. And while lenacapavir may be more effective, it may also be difficult to ensure that people keep up with twice-yearly shots.
Dr. Weinberger’s new study suggests that just one shot of TIPs may keep H.I.V. at low levels — permanently. Not only would this treatment hold off the development of AIDS, but it might make it harder for people to transmit H.I.V. to others.
Asher Leeks, a virologist at Yale University who was not involved in the research, said that it represented a big step forward in the study of so-called cheating viruses. Researchers have been investigating them for decades, but only in recent years have scientists like Dr. Weinberger tried turning them into medical treatments.
Dr. Leeks said that other viruses might also be vulnerable to the same strategy. “In principle, it’s a universal approach to developing antivirals,” he said.
But treatments based on cheating viruses would also raise new ethical questions, said Ben tenOever, a virologist at New York University. Dr. Weinberger’s TIPs inserts themselves into the DNA of a patient’s immune cells. As a result, it becomes a permanent part of their bodies. If they turn out to have unexpected side effects, it may not be possible to remove them.
It’s also conceivable that people with TIPs can spread them to others. If doctors obtain consent from patients to treat them with TIPs, they cannot receive consent from anyone else who is infected with them.
“As the data clearly shows, the H.I.V. TIP works,” Dr. tenOever said. “I am just not sure the world is ready for it.”
Copyright 2024 The New York Times Company. Reprinted with permission.