Cozzi-Lepri, AlessandroAlessandroCozzi-LepriNoguera-Julian, MarcMarcNoguera-JulianDi Giallonardo, FrancescaFrancescaDi GiallonardoSchuurman, RobRobSchuurmanDäumer, MartinMartinDäumerAitken, SueSueAitkenCeccherini-Silberstein, FrancescaFrancescaCeccherini-SilbersteinD'Arminio Monforte, AntonellaAntonellaD'Arminio MonforteGeretti, Anna MariaAnna MariaGerettiBooth, Clare LClare LBoothKaiser, RolfRolfKaiserMichalik, ClaudiaClaudiaMichalikJansen, KlausKlausJansenMasquelier, BernardBernardMasquelierBellecave, PantxikaPantxikaBellecaveKouyos, Roger DRoger DKouyosCastro, ErikaErikaCastroFurrer, HansjakobHansjakobFurrer0000-0002-1375-3146Schultze, AnnaAnnaSchultzeGünthard, Huldrych FHuldrych FGünthardBrun-Vezinet, FrancoiseFrancoiseBrun-VezinetParedes, RogerRogerParedesMetzner, Karin JKarin JMetzner2024-10-232024-10-232015https://boris-portal.unibe.ch/handle/20.500.12422/127029OBJECTIVES It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.enCHAINEuropean multicentre studyantiretroviral therapyminority drug-resistantHIV-1 variants600 - Technology::610 - Medicine & healtharticle10.7892/boris.594942533616610.1093/jac/dku426