Virological outcomes, resistance profile and viral evolution of lenacapavir-based regimens in heavily treatment-experienced people: data from the PRESTIGIO Registry

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Background: Lenacapavir (LEN) is a first-in-class, long-acting HIV-1 capsid inhibitor, approved for the treatment of heavily treatment-experienced (HTE) people with HIV (PWH) with multidrug resistance (MDR). To date, few data are available on resistance profiles in real life. Methods: Paired plasma and PBMC samples from nine HTE PWH with MDR enrolled in the PRESTIGIO Registry receiving LEN in combination with an optimized background regimen were collected before (baseline) and during LEN treatment. Next-generation sequencing was performed using in-house protocols. LEN susceptibility was assessed by single-cycle assay. Intra-patient viral evolution was evaluated through quasispecies distance analysis. Results: At baseline, no major LEN resistance-associated mutations were detected; the accessory capsid polymorphism T107A was identified as a minority variant (5.9%) in one case, with phenotypic assays confirming full LEN susceptibility (mean fold-change: 1.2). Participants received LEN for a median [IQR] of 19.8 [18.5–23.2] months. Two individuals started LEN with undetectable viremia and maintained suppression. The other seven participants were viremic; six achieved viral suppression, with one experiencing a blip. One low-adherent participant exhibited persistent viremia with Q67K and K70H as the majority variants in both plasma (98.5%; 97.8%) and PBMCs (75.7%; 75.6%), conferring a 2081-fold reduction in LEN susceptibility. Intra-host variability in the capsid and pol regions remained low over time and across compartments. Conclusions: In this case series of HTE PWH with MDR, LEN was highly associated with maintenance or achievement of virological suppression and limited virus evolution, with only one participant remaining viremic and showing a majority highly LEN-resistant variant.
Funding Information
  • ViiV Healthcare
  • Gilead Sciences

This publication has 21 references indexed in Scilit: