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Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Cozzi-Lepri Alessandro, Noguera-Julian Marc, Di Giallonardo Francesca, Schuurman Rob, Däumer Martin, Aitken Sue, Ceccherini-Silberstein Francesca, D'Arminio Monforte Antonella, Geretti Anna Maria, Booth Clare L, Kaiser Rolf, Michalik Claudia, Jansen Klaus, Masquelier Bernard, Bellecave Pantxika, Kouyos Roger D, Castro Erika, Furrer Hansjakob, Schultze Anna, Günthard Huldrych F, Brun-Vezinet Francoise, Paredes Roger, Metzner Karin J,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal The Journal of antimicrobial chemotherapy
Volume (Issue) 70(3)
Page(s) 930 - 40
Title of proceedings The Journal of antimicrobial chemotherapy
DOI 10.1093/jac/dku426

Open Access

Type of Open Access Publisher (Gold Open Access)


It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. 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. 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. Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.