The triplet regimen of lenacapavir plus teropavimab and zinlirvimab was safe and well-tolerated in patients being treated for HIV-1, according to early study findings.
Mehri S. McKellar, MD, of Duke University School of Medicine, and colleagues evaluated safety and tolerability data from a phase 1b and phase 2 study of the triplet therapy. They presented their findings at IDWeek 2025.
The pooled analysis included 84 participants (phase 1b, n=31; phase 2, n=53) with a median age of 46 years, most of whom were men. At baseline, patients had a mean CD4+ T-cell count of 838 cells/μL. All patients enrolled were virologically suppressed adults with HIV-1.
In the phase 1b trial, researchers randomly selected patients 1:1 to receive one 927 mg subcutaneous (SC) dose of lenacapavir with oral loading plus 30 mg/kg intravenous (IV) teropavimab, and either 10 mg/kg or 30 mg/kg IV zinlirvimab.
The phase 2 study randomized patients 2:1 to switch to a twice-yearly regimen of 927 mg SC lenacapavir with oral loading, 2550 mg IV teropavimab, and 2550 mg IV zinlirvimab, or to continue a daily oral stable baseline regimen through Week 52.
Both studies showed a maintained virologic suppression for 6 months after one dose.
In addition to tolerability, the researchers also investigated safety, such as the effects of anti-drug antibodies (ADAs) against teropavimab and zinlirvimab. Safety and ADA data were pooled through Week 26.
Study findings, which McKellar discussed at IDWeek 2025, demonstrated a favorable tolerability among patients in both studies.
Treatment-emergent adverse events, excluding injection site reactions (ISRs), were experienced by 66.7% of patients, with most being grade 1 (35.7%). Although most ISRs related to lenacapavir were mild, they were seen in 65.5% of patients. Furthermore, there were no infusion-related reactions, serious adverse events (AEs), or AEs leading to study drug or study discontinuation.
ADAs against teropavimab were found in 11 patients and against zinlirvimab in 15 patients. However, these antibodies were mostly present at low levels and did not affect safety.
While these results are positive, the regimen will continue to be studied in the ongoing phase 2 trial.
Reference
Workowski K, et al. IDWeek 2025. P-365
