Evaluating Lenacapavir and bNAbs in HIV-1

Key Takeaways

• Week-26 virologic control was broadly similar between a long-acting regimen and continued oral ART in this phase 2 comparison.
• Adverse-event rates were broadly comparable after excluding injection-site reactions, and no serious adverse events, deaths, or adverse events leading to discontinuation were reported in the active-treatment arm.

A twice-yearly regimen of lenacapavir plus teropavimab and zinlirvimab maintained suppression through 26 weeks for most adults with HIV-1 already suppressed on oral ART in a multicenter phase 2 comparison.

The trial was randomized, open-label, and active-controlled, with the primary endpoint defined as the proportion with HIV-1 RNA 50 copies per mL or higher at week 26. The study ran at 34 sites across Australia, Canada, and the USA during enrollment. Adults had HIV-1 RNA below 50 copies per mL on ART and virus highly susceptible to teropavimab and zinlirvimab, defined as a 90% inhibitory concentration of 2 micrograms per mL or less. Of 241 people screened, 80 were enrolled and assigned in a 2:1 ratio. The active group received subcutaneous lenacapavir 927 mg with oral loading plus intravenous teropavimab and zinlirvimab, both 2550 mg, twice yearly, while controls continued stable baseline oral ART.

At week 26, 1 of 53 participants, 1.9% with a 95% CI of 0.0 to 10.1, in the lenacapavir-bNAb group had HIV-1 RNA of 50 copies per mL or higher. In the oral-regimen group, 0 of 27 participants met that endpoint, with a 95% CI of 0.0 to 12.8. One participant in each group had no virological data under the FDA Snapshot Algorithm at week 26. Virologic control at week 26 was therefore broadly similar between groups in this open-label phase 2 comparison.

Excluding subcutaneous lenacapavir injection-site reactions, treatment-emergent adverse events occurred in 36 participants (68%) in the lenacapavir-bNAb arm and 17 participants (63%) in the oral-ART arm. Injection-site reactions were reported in 33 participants and were predominantly grade 1. In the active-treatment group, there were no infusion-related reactions to the broadly neutralising antibodies and no study drug-related grade 3 or worse adverse events. There were also no serious adverse events, no deaths, and no adverse events leading to discontinuation through week 26.