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Lenacapavir + two antibodies

As mentioned in the previous article, some antibodies have powerful anti-HIV effects. Researchers at several research centres in Canada, the U.S. and Australia tested a combination of two antibodies: teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS). These were given in an intravenous infusion at a dose of 2,550 mg. In addition, participants received injectable lenacapavir, a long-acting anti-HIV drug, at a dose of 927 mg. Around the time the antibodies were infused, participants also received oral formulations of this drug (600 mg) for two consecutive days to rapidly raise the levels of lenacapavir in the blood.

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The antibodies impair HIV’s ability to attach itself to and thereby infect cells. Lenacapavir also impairs HIV’s ability to infect cells.

Prior to entering the study, potential participants had been on oral ART for at least one year with a suppressed viral load and had stable CD4+ cell counts.

Potential participants had blood samples drawn to check if their HIV was susceptible to the antibodies that were going to be used. Only participants with HIV susceptible to the antibodies moved beyond this stage.

Next, participants were randomly assigned to one of two groups in a 2:1 ratio:

  • cease ART and immediately begin infusions of antibodies followed by infusions (and oral doses) of lenacapavir – 53 people
  • continue with oral ART – 27 people

These interventions would continue for 52 weeks.

The average profile of participants upon entering the study was as follows:

  • age – 50 years
  • 85% assigned male at birth; 15% assigned female at birth
  • most participants were White, followed by Black people
  • body mass index (BMI) – 30 kg/m2
  • CD4+ count – 700 cells/mm3
  • more than 70% of participants were from the U.S.

Results

Most participants, regardless of intervention, maintained viral suppression (less than 50 copies/mL), distributed as follows:

  • antibodies + lenacapavir – 96%
  • continued oral ART – 96%

No data were available for two people—one in each group—as they had discontinued the study due to moving or the development of cancer (unrelated to the study medicines). 

One person had a detectable viral load while on antibody therapy + lenacapavir. This person had been taking Biktarvy (bictegravir + TAF + FTC) at the start of the study prior to receiving antibodies. By the 24th week, they had a viral load greater than 100,000 copies/mL. HIV in this person’s blood had lost its susceptibility to zinlirvimab. They also had HIV that was resistant to lenacapavir. Analysis of blood samples from this person suggested that levels of lenacapavir in their blood began to mysteriously fall 12 weeks after they were first infused with the drug. The person left the study and was restarted on Biktarvy; within 12 weeks they once more had a suppressed viral load. 

Adverse effects

Lenacapavir is known to cause injection site reactions—temporary mild-to-moderate pain, swelling and sometimes nodules (persistent small bumps) can form. Many people (62%) in the study developed injection site reactions to lenacapavir; these were mostly mild. A total of 38% of people who received lenacapavir developed nodules at the injection site. Twenty percent reported temporary pain.

No participants reported infusion site reactions to the antibodies.

Five people who received infusions developed diarrhea (vs. one person who was on continued oral ART).

Bear in mind

The present study’s results are exciting in that it is possible for many people (in theory) to maintain viral suppression with a combination of infusions of antibodies and lenacapavir injections given once every six months.

A major issue is screening people for HIV that is susceptible to the antibodies used. For instance, in the present study, 241 people were screened but the assay failed in 40 people. This left the researchers with susceptibility results on 200 people, of whom only about 80 were randomized in the trial. Thus, antibody therapy will not be for every person with HIV.

—Sean R. Hosein

REFERENCE:

Mponponsuo K, McMahon JH, Gorgos L, et al. Efficacy and safety of lenacapavir, teropavimab, and zinlirvimab: Phase II week 26 primary outcome. Program and abstracts of the 32nd Conference on Retroviruses and Opportunistic Infections, March 9-12, 2025, San Francisco. Abstract 151.