One Experimental Antibody Dose Kept SIV in Remission for Four Years in a Monkey

Twenty newborn rhesus macaques were infected with SIV, the monkey relative of HIV, and one of them, years later, still has no detectable virus in its blood. That animal is the longest-running result in a study from the University of California, Davis, published in Nature Microbiology, and it comes from a single dose of an experimental antibody given alongside early drug treatment.

The problem the team set out to attack is a familiar one. HIV can go quiet without leaving the body. It hides inside immune cells, inserting its genetic material into the cell's DNA, and these dormant cells form what is called the latent viral reservoir. Antiretroviral drugs keep the virus from multiplying but cannot clear it from those cells. Because dormant cells make no viral proteins, the immune system has trouble recognizing them. When medication stops, the virus can start up again.

Virologist Jesse Deere and immunologist Dennis Hartigan-O'Connor, along with their colleagues, tried an approach that does not require finding each infected cell. Instead, the antibody binds two proteins at once: CCR5, which HIV and SIV can use to enter cells, and CD3, a protein complex on T cells. That pairing steers T cells toward cells carrying CCR5, including cells that might harbor the virus and cells it could infect later. Interest in shrinking reservoirs also grows out of rare cases of lasting HIV remission after stem-cell transplants, which were done to treat cancer. This experiment asked whether an antibody could do something similar.

The researchers exposed 25 newborn rhesus macaques to SIV, and 20 became infected. A week later, all began antiretroviral treatment. The animals had been randomly assigned beforehand to three groups: drugs alone; drugs plus a single dose of the CCR5/CD3 antibody; or drugs plus a different antibody aimed at CD4. Antibody treatment started two days after the drugs. After 18 weeks, the drugs were stopped to see whether the virus would come back.

In every animal that received drugs alone, the virus reappeared in the blood within a week. In the CD4 antibody group, six of eight animals rebounded within seven days, though one stayed free of detectable virus through the end of follow-up. Some animals given the CCR5/CD3 antibody fared much better. Four showed no virus in their blood for more than three months. In two of them it returned after 97 and 173 days. A third had not rebounded when follow-up ended at around 29 weeks. The longest-followed animal went four years.

The authors call this remission, a term that does not by itself mean the infection is gone. To probe further, they studied three animals in sustained remission: two given the CCR5/CD3 antibody and one given the CD4 antibody. They temporarily depleted CD8 T cells, which help control viral infections, reasoning that if those cells were holding a hidden infection in check, removing them might let it surface. No rebound occurred. Tissue tests found no viral genetic material, and attempts to recover infectious virus from lymph-node cells failed. Together these results support a substantial reduction in the reservoir.

There is one caveat in the data. A single sample from the monkey followed for four years gave a tiny signal of possible viral RNA. The team could not conclusively rule out contamination, and found no accompanying viral DNA and no return of virus in the blood.

The study was small, and treatment began soon after infection. The researchers chose infant monkeys partly because they can rebuild immune cells quickly, so it is unknown whether adults or people with longstanding infections would respond similarly. The antibody also hits uninfected immune cells. Animals generally tolerated it, with mild reactions that resolved within hours, but any effect on defenses against other infections still needs investigation. The authors conclude that using the host immune system to target CCR5-expressing cells may be a surprisingly effective route to a cure, at least for infants treated soon after infection.

The approach has not been tested in people. Its effectiveness and safety in humans remain the open questions.