Results of a study on lenacapavir and two broadly neutralizing antibodies were presented at CROI 2025.

At the Conference on Retroviruses and Opportunistic Infections (CROI 2025) in San Francisco, results were presented from a Phase II study examining the efficacy of a combination of lenacapavir (TN Sunlenca) and two broadly neutralizing antibodies (bNAbs) – teropavimab and zinlirvimab. The study results indicate that this regimen could form the basis of a complete therapy with drug administration once every six months.

As you know, lenacapavir is already used to treat patients with multidrug resistance, but it is only effective in combination with daily oral ARV drugs. Broadly neutralizing antibodies are being considered as a promising solution to this problem, as they can attack stable areas of the virus and provide long-term HIV suppression. Teropavimab (GS-5423) prevents the virus from entering cells, and zinlirvimab (GS-2872) binds to the V3 loop of the HIV envelope. Both antibodies have been modified to increase their half-life and reduce the frequency of administration.

The Phase II study involved 80 people with suppressed viral load who were highly sensitive to both antibodies. After preliminary screening for sensitivity, participants were randomized into two groups: the first group switched to the new regimen of lenacapavir + two antibodies, and the second continued to take daily oral ARV drugs. After 26 weeks, 96% of participants in both groups maintained viral suppression, and the level of CD4 cells increased, with no significant differences between the groups. Lenacapavir, teropavimab, and zinlirvimab maintained stable concentrations in the body for six months. Only one person in the first group experienced an increase in viral load, but viral suppression was restored after returning to standard therapy.

The combination of lenacapavir and two antibodies also demonstrated good tolerability. No serious side effects or cases of therapy discontinuation due to adverse events were identified. The only common side effect was local reactions to the lenacapavir injection – 40% of participants developed small subcutaneous nodules. However, pain and other local reactions were rare and mild. Also, none of the participants had infusion reactions to teropavimab and zinlirvimab, which confirms the safety of the new combination.

According to experts, the data suggest that the combination of lenacapavir and two bNAbs could become a new, complete long-acting therapy that could eliminate the need for patients to take daily pills. »