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Extensive drug resistance during low-level HIV viraemia while taking NNRTI-based ART supports lowering the viral load threshold for regimen switch in resource-limited settings: a pre-planned analysis from the SESOTHO trial

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Brown Jennifer Anne, Amstutz Alain, Nsakala Bienvenu Lengo, Seeburg Ulrike, Vanobberghen Fiona, Muhairwe Josephine, Klimkait Thomas, Daniel Labhardt Niklaus,
Project Supporting Lesotho on the way towards the UNAIDS 90-90-90 targets: Operational and clinical research addressing HIV/AIDS care in resource-limited settings
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Original article (peer-reviewed)

Journal Journal of Antimicrobial Chemotherapy
Page(s) dkab025
Title of proceedings Journal of Antimicrobial Chemotherapy
DOI 10.1093/jac/dkab025

Open Access

Abstract

AbstractObjectivesWHO guidelines on ART define the HIV-1 viral load (VL) threshold for treatment failure at 1000 copies/mL. The Switch Either near Suppression Or THOusand (SESOTHO) trial, conducted in Lesotho from 2017 to 2020, found that patients with persistent viraemia below this threshold (100–999 copies/mL) benefit from switching to second-line ART. This pre-planned nested study assesses the prevalence of resistance-associated mutations (RAMs) in SESOTHO trial participants.MethodsThe SESOTHO trial [registered at ClinicalTrials.gov (NCT03088241)] enrolled 80 persons taking NNRTI-based first-line ART with low-level HIV-1 viraemia (100–999 copies/mL) and randomized them (1:1) to switch to a PI-based second-line regimen (switch) or continue on first-line therapy (control). We sequenced relevant regions of the viral pol gene using plasma samples obtained at enrolment and 36 weeks. RAMs were classified with the Stanford HIV Drug Resistance Database.ResultsSequencing data were obtained for 37/80 (46%) participants at baseline and 26/48 (54%) participants without viral suppression to <50 copies/mL at 36 weeks (21 control participants and 5 switch participants). At baseline, 31/37 (84%) participants harboured high-level resistance to at least two drugs of their current regimen. At 36 weeks, 17/21 (81%) control participants harboured resistance to at least two drugs of their current regimen, while no PI-associated resistance was detected in the 5 switch participants with ongoing viraemia.ConclusionsAmong persons with low-level viraemia while taking NNRTI-based first-line ART enrolled in the SESOTHO trial, the majority harboured HIV-1 with RAMs that necessitate ART modification. These findings support lowering the VL threshold triggering a switch to second-line ART in future WHO guidelines.
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