Contents

The Rio study – powerful antibodies help give people a break from treatment

HIV treatment has advanced tremendously since 1996. Today, treatments are much safer, and an entire regimen can be taken once daily in a pill or ultimately once every two months via injection.

Receive TreatmentUpdate in your inbox:

However, despite a good track record of safety with modern antiretroviral therapy (ART), some researchers and pharmaceutical companies are concerned that since HIV treatment is lifelong, there is the potential for patients to develop side effects after decades of exposure to ART.

Some companies, such as ViiV Healthcare, have developed regimens consisting of only two drugs, as follows:

  • Dovato – a pill containing dolutegravir + 3TC
  • Juluca – a pill containing dolutegravir + rilpivirine
  • Cabenuva – this contains long-acting formulations of dolutegravir + rilpivirine and is ultimately injected every two months

Other two-drug regimens under development for HIV treatment include the following:

  • doravirine + islatravir
  • lenacapavir + islatravir

Studies of super antibodies

Scientists have developed antibodies with potent activity against HIV. The technical term for such antibodies is broadly neutralizing antibodies (bNAbs); they are sometimes called super antibodies because of their potency against HIV.

The idea behind bNAbs is to offer them to patients whose HIV is already suppressed on ART. Potential bNAb users will be screened for HIV that is susceptible to these antibodies. People with susceptible HIV will then be switched from their pre-existing ART to a combination of two or more antibodies given every six months. Antibodies can either be given intravenously or via injection. As using antibodies to replace ART is an experimental approach, much remains to be understood (such as the best way to administer the antibodies, the duration of effectiveness, and so on).

The Rio study

A team of researchers in the UK and Denmark conducted a study called Rio. In this study, participants who were diagnosed early in HIV infection were randomly assigned to receive ART for at least 12 months to suppress their HIV. At the end of this time, they were randomly assigned to receive one of the following interventions after cessation of ART (they were not told at the time of the infusion what they were receiving):

  • infusions of two antibodies (3NBC117-LS + 10-1074-LS) – 34 people
  • infusions of placebo – 34 people

Participants were monitored with weekly blood tests for the first eight weeks with a focus on changes to viral load and CD4+ cell counts. After this, they had blood drawn twice monthly.

Participants who remained virally suppressed after 20 weeks could then receive another intravenous infusion (which was also blinded) and continue to be monitored.

Participants whose HIV resurged or whose CD4+ counts decreased significantly were withdrawn from the study.

The average profile of participants at the start of the study was as follows:

  • age – 40 years
  • all were cisgender men
  • body mass index (BMI) – 25 kg/m2
  • most participants (80%) were White
  • CD4+ count – 800 cells/mm3 (recall that participants were enrolled in the early stages of HIV infection)
  • all were virally suppressed, as they had been on ART
  • 80% of participants had HIV clade B; this is the variant, or strain, of HIV that is most common in Western Europe, North America, Australia and New Zealand

Partners of participants were offered HIV testing and free PrEP.

Results

Twenty weeks after the first infusion, the proportions of participants who remained virally suppressed were as follows:

  • antibodies – 75%
  • placebo – 9%

This difference was highly statistically significant; that is, not likely due to chance alone. It suggests that just one infusion of two potent antibodies can maintain viral suppression for many people with HIV for 20 consecutive weeks.

After week 20

Twenty weeks after the first infusion, most participants who remained suppressed received a second infusion of antibodies. In total, 50% of people who received a second dose of antibodies remained virally suppressed for 62 weeks. So far, 39% of these participants have remained virally suppressed at week 72 of the study.

Only two people who had received an infusion of placebo and who were still suppressed at week 20 received another infusion and remained virally suppressed at week 120.

Adverse events

One person died, but researchers stated that this was unrelated to exposure to bNAbs or time off ART (details were not provided). No one developed reactions to infusions of antibodies or placebo.

Everyone who restarted ART did so because of resurging viral loads and not because of significant CD4+ cell decreases. 

On average, people who received bNAbs had a viral load of 55,000 copies/mL when restarting ART. The viral load among people who received placebo was 1 million copies/mL.

When participants restarted ART, it took on average 12 weeks of treatment for their viral load to fall below the 50 copy/mL mark. For people with very high viral loads (1 million copies or more), in some cases it could take up to 24 weeks of ART to resuppress their virus.

Why was virus suppressed off ART?

In most of the people who received antibodies, it is possible that the antibodies interacted with their immune system in some way to help them better control HIV. This effect of super antibodies is being investigated. For instance, research suggests that bNAbs decreased the pool of infected cells in the body and enhanced the immune system’s ability to attack HIV-infected cells.

It is possible that the people on placebo who had sustained HIV suppression did so because they may have had pre-existing mechanisms that somehow naturally controlled HIV. 

Bear in mind

The Rio data are exciting, but many challenges remain. For instance, many people will not have HIV that is susceptible to the antibodies used. Also, the frequency of viral load monitoring—initially weekly then every two weeks—can be stressful for people who worry about possibly infecting their partners or having their health deteriorate. In Rio, no partners were infected, and no one was harmed by staying off ART with controlled HIV.

Rio is an important clinical trial that will likely pave the way for many future studies of interventions (antibodies, drugs, and so on) that seek to help people’s immune systems develop the ability to successfully control HIV for months so that they do not need to take ART. Enrolling in such studies is important and helps to advance the field.

Future trials need to enroll more women, people of different ethno-racial groups and those who have different strains or clades of HIV.

—Sean R. Hosein

REFERENCE:

Fidler S, Lee MJ, Collins S, et al. RIO: A randomised placebo-controlled study of 2 LS-bNAbs in people treated in early HIV. Program and abstracts of the 32nd Conference on Retroviruses and Opportunistic Infections, March 9-12, 2025, San Francisco. Abstract 107.