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A. Cozzi-Lepri, M. Noguera-Julián, Francesca Di Giallonardo, R. Schuurman, M. Däumer, S. Aitken, F. Ceccherini‐Silberstein, A. d’Arminio Monforte, A. Geretti, C. Booth, R. Kaiser, C. Michalik, K. Jansen, B. Masquelier, P. Bellecave, R. Kouyos, E. Castro, H. Furrer, A. Schultze, H. Günthard, F. Brun-vezinet, R. Paredes, K. Metzner, R. Paredes, K. Metzner, A. Cozzi-Lepri, R. Schuurman, F. Brun-vezinet, H. Günthard, F. Ceccherini‐Silberstein, R. Kaiser, A. Geretti, N. Brockmeyer, B. Masquelier, F. Dabis, M. Bruyand, G. Chêne, S. Lawson-Ayayi, R. Thiébaut, L. Wittkop, K. André, F. Bonnal, F. Bonnet, N. Bernard, L. Caunègre, C. Cazanave, J. Ceccaldi, I. Chossat, K. Courtaud, F. Dauchy, S. de Witte, M. Dupon, A. Dupont, P. Duffau, H. Dutronc, S. Farbos, V. Gaborieau, M. Gemain, Y. Gérard, C. Greib, M. Hessamfar, D. Lacoste, P. Lataste, E. Lazaro, M. Longy‐Boursier, D. Malvy, J. Meraud, P. Mercié, E. Monlun, P. Morlat, D. Neau, A. Ochoa, J. Pellegrin, T. Pistone, M. Receveur, J. Schmeltz, S. Tchamgoué, M. Vandenhende, M. Vareil, J. Viallard, J. Moreau, I. Pellegrin, H. Fleury, M. Lafon, B. Masquelier, S. Reigadas, P. Trimoulet, S. Bouchet, D. Breilh, M. Molimard, K. Titier, F. Haramburu, G. Miremont-Salamé, M. Blaizeau, M. Decoin, J. Delaune, S. Delveaux, C. d'Ivernois, C. Hanapier, O. Leleux, E. Lenaud, B. Uwamaliya-Nziyumvira, X. Sicard, S. Geffard, F. le Marec, V. Conte, A. Frosch, J. Leray, G. Palmer, D. Touchard, M. Losso, M. Kundro, J. M. Ramos Mejía, N. Vetter, R. Zangerle, I. Karpov, A. Vassilenko, V. Mitsura, O. Suetnov, N. Clumeck, S. D. de Wit, M. Delforge, E. Florence, L. Vandekerckhove, V. Hadžiosmanović, K. Kostov, J. Begovac, L. Machala, D. Jilich, D. Sedláček, J. Nielsen, G. Kronborg, T. Benfield, M. Larsen, J. Gerstoft, T. Katzenstein, A. Hansen, P. Skinhøj, C. Pedersen, L. Ostergaard, U. B. Dragsted, L. Nielsen, K. Zilmer, J. Šmidt, M. Ristola, C. Katlama, J. Viard, P. Girard, P. Vanhems, C. Pradier, C. Duvivier, J. Rockstroh, R. Schmidt, J. van Lunzen, O. Degen, H. Stellbrink, M. Bickel, J. Bogner, G. Fätkenheuer, J. Kosmidis, P. Gargalianos, G. Xylomenos, J. Perdios, H. Sambatakou, D. Bánhegyi, M. Gottfredsson, F. Mulcahy, I. Yust, D. Turner, M. Burke, S. Pollack, G. HassounRambam, H. Elinav, M. HaouziHadassah, R. EspositoI, F. Mazzotta, V. Vullo, M. Moroni, M. Andreoni, G. Angarano, A. Antinori, F. Castelli, R. Cauda, G. di Perri, M. Galli, R. Iardino, G. Ippolito, A. Lazzarin, C. Perno, F. von Schloesser, P. Viale, A. Monforte, A. Castagna, F. Ceccherini‐Silberstein, A. Cozzi-Lepri, E. Girardi, S. Lo Caputo, C. Mussini, M. Puoti, A. Ammassari, C. Balotta, P. Bonfanti, S. Bonora, M. Borderi, M. Capobianchi, A. Cingolani, P. Cinque, A. De Luca, A. di Biagio, N. Gianotti, A. Gori, G. Guaraldi, G. Lapadula, M. Lichtner, G. Madeddu, F. Maggiolo, G. Marchetti, S. Marcotullio, L. Monno, E. Quiros Roldan, S. Rusconi, P. Cicconi, I. Fanti, T. Formenti, L. Galli, P. Lorenzini, F. Carletti, S. Carrara, A. Castrogiovanni, A. di Caro, F. Petrone, G. Prota, S. Quartu, A. Giacometti, A. Costantini, S. Mazzoccato, C. Santoro, C. Suardi, E. Vanino, G. Verucchi, C. Minardi, T. Quirino, C. Abeli, P. Manconi, P. Piano, J. Vecchiet, K. Falasca, L. Sighinolfi, D. Segala, G. Cassola, C. Viscoli, A. Alessandrini, R. Piscopo, G. Mazzarello, C. Mastroianni, V. Belvisi, I. Caramma, A. Chiodera, A. Castelli, G. Rizzardini, A. d’Arminio Monforte, A. Ridolfo, R. Piolini, S. Salpietro, L. Carenzi, M. Moioli, C. Tincati, C. Puzzolante, N. Abrescia, A. Chirianni, M. G. Guida, M. Gargiulo, F. Baldelli, D. Francisci, G. Parruti, T. Ursini, G. Magnani, M. Ursitti, A. D’Avino, L. Gallo, E. Nicastri, R. Acinapura, M. Capozzi, R. Libertone, G. Tebano, A. Cattelan, L. Sasset, M. Mura, B. Rossetti, P. Caramello, G. Orofino, M. Sciandra, M. Bassetti, A. Londero, G. Pellizzer, V. Manfrin, N. Brockmeyer, A. Skaletz‐Rorowski, S. Dupke, A. Baumgarten, A. Carganico, S. Köppe, P. Kreckel, E. Lauenroth-Mai, M. Freiwald-Rausch, J. Gölz, A. Moll, M. Zeitz, M. Hower, S. Reuter, B. Jensen, T. Harrer, S. Esser, H. Brodt, A. Plettenberg, A. Stöhr, T. Buhk, M. Stoll, B. Kuhlmann, F. Mosthaf, A. Rieke, W. Becker, R. Volkert, H. Jäger, H. Hartl, A. Mutz, A. Ulmer, M. Müller, V. Aubert, J. Barth, M. Battegay, E. Bernasconi, J. Böni, H. Bucher, C. Burton-Jeangros, A. Calmy, M. Cavassini, M. Egger, L. Elzi, J. Fehr, J. Fellay, H. Furrer, C. Fux, M. Gorgievski, H. Günthard, D. Haerry, B. Hasse, H. Hirsch, I. Hösli, C. Kahlert, L. Kaiser, O. Keiser, T. Klimkait, H. Kovari, R. Kouyos, B. Ledergerber, G. Martinetti, B. Martinez de Tejada, K. Metzner, N. Müller, D. Nadal, G. Pantaleo, A. Rauch, S. Regenass, M. Rickenbach, C. Rudin, P. Schmid, D. Schultze, F. Schöni-Affolter, J. Schüpbach, R. Speck, C. Staehelin, P. Tarr, A. Telenti, A. Trkola, P. Vernazza, R. Weber, S. Yerly
117 21. 10. 2014.

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

Objectives 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.


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