Ερευνητικό υλικό ΕΚΠΑ

Primary resistance to integrase strand-transfer inhibitors in Europe

Αγγλικά

Objectives: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. Methods: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score=10 to at least one InSTI. To rule out circulation of minority InSTIresistant HIV, 65 samples were selected for 454 integrase sequencing. Results: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIswere detected. Eleven (4%) subjects hadmutations at resistance-associated positions with an HIVdb score =10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutationsweredetected, whereas integrase substitutionswithanHIVdbscore=10were found in8(14.3%) individuals. Conclusions:No signature InSTI-resistant variantswere circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistancewere not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

2015

Casadellà, M.
van Ham, P.M.
Noguera-Julian, M.
van Kessel, A.
Pou, C.
Hofstra, L.M.
Santos, J.R.
Garcia, F.
Struck, D.
Alexiev, I.
Bakken Kran, A.M.
Hoepelman, A.I.
Kostrikis, L.G.
Somogyi, S.
Liitsola, K.
Linka, M.
Nielsen, C.
Otelea, D.
Paraskevis, D.
Poljak, M.
Puchhammer-Stöckl, E.
Staneková, D.
Stanojevic, M.
Van Laethem, K.
Zidovec Lepej, S.
Clotet, B.
Boucher, C.A.B.
Paredes, R.
Wensing, A.M.J.
Puchhammer-Stöckl, E.
Sarcletti, M.
Schmied, B.
Geit, M.
Balluch, G.
Vandamme, A.M.
Vercauteren, J.
Derdelinckx, I.
Sasse, A.
Bogaert, M.
Ceunen, H.
De Roo, A.
De Wit, S.
Echahidi, F.
Fransen, K.
Goffard, J.C.
Goubau, P.
Goudeseune, E.
Yombi, J.C.
Lacor, P.
Liesnard, C.
Moutschen, M.
Pierard, D.
Rens, R.
Schrooten, Y.
Vaira, D.
Vandekerckhove, L.P.
Van den Heuvel, A.
Van Der Gucht, B.
Van Ranst, M.
Van Wijngaerden, E.
Vandercam, B.
Vekemans, M.
Verhofstede, C.
Clumeck, N.
Van Laethem, K.
Beshkov, D.
Alexiev, I.
Zidovec Lepej, S.
Begovac, J.
Demetriades, I.
Kousiappa, I.
Demetriou, V.
Hezka, J.
Linka, M.
Machala, L.
Maly, M.
Nielsen, C.
Jørgensen, L.B.
Gerstoft, J.
Mathiesen, L.
Pedersen, C.
Nielsen, H.
Laursen, A.
Kvinesdal, B.
Liitsola, K.
Ristola, M.
Suni, J.
Sutinen, J.
Hamouda, O.
Kücherer, C.
Berg, T.
Braun, P.
Poggensee, G.
Däumer, M.
Eberle, J.
Heiken, H.
Kaiser, R.
Knechten, H.
Korn, K.
Müller, H.
Neifer, S.
Schmidt, B.
Walter, H.
Gunsenheimer-Bartmeyer, B.
Harrer, T.
Paraskevis, D.
Hatzakis, A.
Magiorkinis, E.
Hatzitheodorou, E.
Haida, C.
Zavitsanou, A.
Magiorkinis, G.
Lazanas, M.
Chini, M.
Magafas, N.
Tsogas, N.
Paparizos, V.
Kourkounti, S.
Antoniadou, A.
Papadopoulos, A.
Panagopoulos, P.
Poulakou, G.
Sakka, V.
Chryssos, G.
Drimis, S.
Gargalianos, P.
Lelekis, M.
Chilomenos, G.
Psichogiou, M.
Daikos, G.L.
Sabatakou, H.
Panos, G.
Haratsis, G.
Kordossis, T.
Kontos, A.
Koratzanis, G.
Theodoridou, M.
Mostrou, G.
Spoulou, V.
Schmit, J.C.
Struck, D.
Hemmer, R.
Arendt, V.
Staub, T.
Schneider, F.
Roman, F.
Wensing, A.M.
Boucher, C.A.
van de Vijver, D.A.
van Kessel, A.
van, P.H.
Brinkman, K.
Op de, E.L.
van der Ende, M.E.
Hoepelman, I.M.
van Kasteren, M.
Juttmann, J.
Kuipers, M.
Langebeek, N.
Richter, C.
Santegoets, R.M.
Schrijnders-Gudde, L.
Schuurman, R.
van de Ven, B.J.
Åsjö, B.
Bakken, A.M.
Ormaasen, V.
Aavitsland, P.
Otelea, D.
Paraschiv, S.
Tudor, A.M.
Jevtovic, D.
Salemovic, D.
Stanekova, D.
Habekova, M.
Mokras, M.
Truska, P.
Poljak, M.
Lunar, M.
Babic, D.
Tomazic, J.
Vidmar, L.
Vovko, T.
Karner, P.
Clotet, B.
Garcia, F.
Domingo, P.
Galindo, M.J.
Miralles, C.
Del, M.A.
Ribera, E.
Iribarren, J.A.
Ruiz, L.
de la Torre, J.
Vidal, F.
Garcia, F.
Paredes, R.
on behalf of the SPREAD programme

The Journal of antimicrobial chemotherapy

Oxford University Press

70

10

2885-2888

dolutegravir; integrase; integrase inhibitor; integrase strand transfer inhibitor; nonnucleoside reverse transcriptase inhibitor; proteinase inhibitor; raltegravir; RNA directed DNA polymerase inhibitor; unclassified drug; integrase; integrase inhibitor; p31 integrase protein, Human immunodeficiency virus 1, amino acid substitution; antiviral resistance; Article; controlled study; cross-sectional study; drug efficacy; Europe; female; gene sequence; genetic variability; human; Human immunodeficiency virus 1; Human immunodeficiency virus 1 infection; Human immunodeficiency virus infected patient; Human immunodeficiency virus prevalence; major clinical study; male; molecular epidemiology; multicenter study; quality control; scoring system; sequence analysis; Stanford HIVdb score; virus gene; CD4 lymphocyte count; clinical trial; DNA sequence; drug effects; genetic variation; genetics; genotype; health survey; highly active antiretroviral therapy; HIV Infections; risk factor; virology; virus load, Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cross-Sectional Studies; Drug Resistance, Viral; Europe; Female; Genetic Variation; Genotype; HIV Infections; HIV Integrase; HIV Integrase Inhibitors; HIV-1; Humans; Male; Population Surveillance; Risk Factors; Sequence Analysis, DNA; Viral Load

https://doi.org/10.1093/jac/dkv202

10.1093/jac/dkv202

https://pergamos.lib.uoa.gr/uoa/dl/object/3060741