# Resistance Analysis of Low-Level Virologic Rebound During HIV-1 Treatment With Lenacapavir and Broadly Neutralizing Antibodies Teropavimab and Zinlirvimab

## TL;DR

A study found that a treatment combining lenacapavir and two antibodies effectively suppressed HIV for 26 weeks with minimal resistance.

## Contribution

The study reports rare resistance to lenacapavir and no resistance to bNAbs during 26 weeks of treatment in HIV patients.

## Key findings

- One participant developed lenacapavir resistance (Q67H mutation) but remained responsive to bNAbs.
- Two participants experienced low-level rebound but showed no resistance to lenacapavir or bNAbs.
- The regimen maintained high virologic suppression with rare resistance, supporting further evaluation.

## Abstract

High rates of virologic suppression were observed in the Phase 1b study (NCT04811040) investigating lenacapavir and two broadly neutralizing antibodies (bNAb), teropavimab (30 mg/kg) and zinlirvimab (10 or 30 mg/kg), in virologically suppressed people with HIV-1 susceptible (IC90 ≤ 2 μg/mL) to both (primary cohort, n = 20) or either (pilot cohort, n = 10) bNAb. We describe resistance analyses through Week (W) 26.

Post-baseline resistance analyses were conducted at virologic failure, and exploratory resistance analyses performed for participants with virologic rebound. Low copy number genotyping methods for capsid and a 1 kb stretch of gp120 from rebound virus were developed, and phenotypic susceptibility assessed.

Virologic failure was observed in 1/30 participants. This primary cohort participant had HIV RNA 155 copies/mL at W16 and developed Q67H in capsid (lenacapavir fold-change 4.7), without resistance to bNAbs; the participant resuppressed on oral antiretrovirals. Two pilot cohort participants, experienced virologic rebound at W26 (55 and 72 copies/mL) and restarted oral antiretrovirals. In exploratory analyses, neither had emergent lenacapavir resistance or altered bNAb susceptibility.

Lenacapavir, teropavimab, and zinlirvimab maintained a high rate of virologic suppression through W26, with rare emergent lenacapavir resistance and no bNAb resistance, supporting further Phase 2 evaluation.

Resistance analysis from a Phase 1b study of lenacapavir with broadly neutralizing antibodies teropavimab and zinlirvimab showed rare emergent lenacapavir resistance and no bNAb resistance during 26 weeks of treatment, supporting further evaluation of this twice-yearly regimen for HIV treatment.