A376s in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

Roger Paredes; Maria Carmen Puertas; Wendy Bannister; Mónica Kisic; Alessandro Cozzi-Lepri; Christian Pou; Rocío Bellido; Gilberto Betancor; Johannes Bogner; Panagiotis Gargalianos; Dénes Bánhegyi; Bonaventura Clotet; Jens Lundgren; Luis Menéndez-Arias; Javier Martinez-Picado; M. Losso; C. Elias; N. Vetter; R. Zangerle; I. Karpov; A. Vassilenko; V. M. Mitsura; O. Suetnov; N. Clumeck; S. De Wit; B. Poll; R. Colebunders; L. Vandekerckhove; V. Hadziosmanovic; K. Kostov; J. Begovac; L. Machala; H. Rozsypal; D. Sedlacek; J. Nielsen; G. Kronborg; T. Benfield; M. Larsen; J. Gerstoft; T. Katzenstein; A. B.E. Hansen; P. Skinhøj; C. Pedersen; L. Oestergaard; K. Zilmer; Jelena Smidt; M. Ristola; C. Katlama; J. P. Viard; P. M. Girard; J. M. Livrozet; P. Vanhems; C. Pradier; F. Dabis; D. Neau; J. Rockstroh; R. Schmidt; J. Van Lunzen; O. Degen; H. J. Stellbrink; S. Staszewski; J. Bogner; G. Fätkenheuer; J. Kosmidis; P. Gargalianos; G. Xylomenos; J. Perdios; G. Panos; A. Filandras; E. Karabatsaki; H. Sambatakou; D. Banhegyi; F. Mulcahy; I. Yust; D. Turner; M. Burke; S. Pollack; G. Hassoun; S. Maayan; S. Vella; R. Esposito; I. Mazeu; C. Mussini; C. Arici; R. Pristera; F. Mazzotta; A. Gabbuti; V. Vullo; M. Lichtner; A. Chirianni; E. Montesarchio; M. Gargiulo; G. Antonucci; F. Iacomi; P. Narciso; C. Vlassi; M. Zaccarelli; A. Lazzarin; R. Finazzi; M. Galli

doi:10.1093/infdis/jir385

A376s in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

Roger Paredes, Maria Carmen Puertas, Wendy Bannister, Mónica Kisic, Alessandro Cozzi-Lepri, Christian Pou, Rocío Bellido, Gilberto Betancor, Johannes Bogner, Panagiotis Gargalianos, Dénes Bánhegyi, Bonaventura Clotet, Jens Lundgren, Luis Menéndez-Arias, Javier Martinez-Picado, M. Losso, C. Elias, N. Vetter, R. Zangerle, I. KarpovA. Vassilenko, V. M. Mitsura, O. Suetnov, N. Clumeck, S. De Wit, B. Poll, R. Colebunders, L. Vandekerckhove, V. Hadziosmanovic, K. Kostov, J. Begovac, L. Machala, H. Rozsypal, D. Sedlacek, J. Nielsen, G. Kronborg, T. Benfield, M. Larsen, J. Gerstoft, T. Katzenstein, A. B.E. Hansen, P. Skinhøj, C. Pedersen, L. Oestergaard, K. Zilmer, Jelena Smidt, M. Ristola, C. Katlama, J. P. Viard, P. M. Girard, J. M. Livrozet, P. Vanhems, C. Pradier, F. Dabis, D. Neau, J. Rockstroh, R. Schmidt, J. Van Lunzen, O. Degen, H. J. Stellbrink, S. Staszewski, J. Bogner, G. Fätkenheuer, J. Kosmidis, P. Gargalianos, G. Xylomenos, J. Perdios, G. Panos, A. Filandras, E. Karabatsaki, H. Sambatakou, D. Banhegyi, F. Mulcahy, I. Yust, D. Turner, M. Burke, S. Pollack, G. Hassoun, S. Maayan, S. Vella, R. Esposito, I. Mazeu, C. Mussini, C. Arici, R. Pristera, F. Mazzotta, A. Gabbuti, V. Vullo, M. Lichtner, A. Chirianni, E. Montesarchio, M. Gargiulo, G. Antonucci, F. Iacomi, P. Narciso, C. Vlassi, M. Zaccarelli, A. Lazzarin, R. Finazzi, M. Galli

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

17 Cites (Scopus)

Resum

Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI susceptibility of single site-directed mutants and patient-derived recombinant viruses. Enzymatic assays also determined the effects of A376S on nevirapine and template-primer binding to HIV-1 RT. Results. Virological failure occurred in 142 of 287 (49%) individuals: 77 receiving nevirapine (67%) and 65 receiving efavirenz (38%) (P < .001). Preexisting A376S was associated with an increased risk of virological failure to nevirapine (relative hazard [RH] = 10.4; 95% confidence interval [CI], 2.0-54.7), but it did not affect efavirenz outcome the same way (RH = 0.5; 95% CI, 0.1-2.2) (P value for interaction 5 .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure to nevirapine-based ART. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Idioma original	Anglès
Pàgines (de-a)	741-752
Revista	Journal of Infectious Diseases
Volum	204
Número	5
DOIs	https://doi.org/10.1093/infdis/jir385
Estat de la publicació	Publicada - 1 de set. 2011

SDG de les Nacions Unides

Aquest resultat contribueix als següents objectius de desenvolupament sostenible.

Accés al document

10.1093/infdis/jir385

Com citar-ho

Paredes, R., Puertas, M. C., Bannister, W., Kisic, M., Cozzi-Lepri, A., Pou, C., Bellido, R., Betancor, G., Bogner, J., Gargalianos, P., Bánhegyi, D., Clotet, B., Lundgren, J., Menéndez-Arias, L., Martinez-Picado, J., Losso, M., Elias, C., Vetter, N., Zangerle, R., ... Galli, M. (2011). A376s in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. Journal of Infectious Diseases, 204(5), 741-752. https://doi.org/10.1093/infdis/jir385

@article{fffda30032d842e9b511879a0265b054,

title = "A376s in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy",

abstract = "Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI susceptibility of single site-directed mutants and patient-derived recombinant viruses. Enzymatic assays also determined the effects of A376S on nevirapine and template-primer binding to HIV-1 RT. Results. Virological failure occurred in 142 of 287 (49%) individuals: 77 receiving nevirapine (67%) and 65 receiving efavirenz (38%) (P < .001). Preexisting A376S was associated with an increased risk of virological failure to nevirapine (relative hazard [RH] = 10.4; 95% confidence interval [CI], 2.0-54.7), but it did not affect efavirenz outcome the same way (RH = 0.5; 95% CI, 0.1-2.2) (P value for interaction 5 .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure to nevirapine-based ART. {\textcopyright} The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.",

author = "Roger Paredes and Puertas, {Maria Carmen} and Wendy Bannister and M{\'o}nica Kisic and Alessandro Cozzi-Lepri and Christian Pou and Roc{\'i}o Bellido and Gilberto Betancor and Johannes Bogner and Panagiotis Gargalianos and D{\'e}nes B{\'a}nhegyi and Bonaventura Clotet and Jens Lundgren and Luis Men{\'e}ndez-Arias and Javier Martinez-Picado and M. Losso and C. Elias and N. Vetter and R. Zangerle and I. Karpov and A. Vassilenko and Mitsura, {V. M.} and O. Suetnov and N. Clumeck and {De Wit}, S. and B. Poll and R. Colebunders and L. Vandekerckhove and V. Hadziosmanovic and K. Kostov and J. Begovac and L. Machala and H. Rozsypal and D. Sedlacek and J. Nielsen and G. Kronborg and T. Benfield and M. Larsen and J. Gerstoft and T. Katzenstein and Hansen, {A. B.E.} and P. Skinh{\o}j and C. Pedersen and L. Oestergaard and K. Zilmer and Jelena Smidt and M. Ristola and C. Katlama and Viard, {J. P.} and Girard, {P. M.} and Livrozet, {J. M.} and P. Vanhems and C. Pradier and F. Dabis and D. Neau and J. Rockstroh and R. Schmidt and {Van Lunzen}, J. and O. Degen and Stellbrink, {H. J.} and S. Staszewski and J. Bogner and G. F{\"a}tkenheuer and J. Kosmidis and P. Gargalianos and G. Xylomenos and J. Perdios and G. Panos and A. Filandras and E. Karabatsaki and H. Sambatakou and D. Banhegyi and F. Mulcahy and I. Yust and D. Turner and M. Burke and S. Pollack and G. Hassoun and S. Maayan and S. Vella and R. Esposito and I. Mazeu and C. Mussini and C. Arici and R. Pristera and F. Mazzotta and A. Gabbuti and V. Vullo and M. Lichtner and A. Chirianni and E. Montesarchio and M. Gargiulo and G. Antonucci and F. Iacomi and P. Narciso and C. Vlassi and M. Zaccarelli and A. Lazzarin and R. Finazzi and M. Galli",

year = "2011",

month = sep,

day = "1",

doi = "10.1093/infdis/jir385",

language = "English",

volume = "204",

pages = "741--752",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

number = "5",

}

Paredes, R, Puertas, MC, Bannister, W, Kisic, M, Cozzi-Lepri, A, Pou, C, Bellido, R, Betancor, G, Bogner, J, Gargalianos, P, Bánhegyi, D, Clotet, B, Lundgren, J, Menéndez-Arias, L, Martinez-Picado, J, Losso, M, Elias, C, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, VM, Suetnov, O, Clumeck, N, De Wit, S, Poll, B, Colebunders, R, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Begovac, J, Machala, L, Rozsypal, H, Sedlacek, D, Nielsen, J, Kronborg, G, Benfield, T, Larsen, M, Gerstoft, J, Katzenstein, T, Hansen, ABE, Skinhøj, P, Pedersen, C, Oestergaard, L, Zilmer, K, Smidt, J, Ristola, M, Katlama, C, Viard, JP, Girard, PM, Livrozet, JM, Vanhems, P, Pradier, C, Dabis, F, Neau, D, Rockstroh, J, Schmidt, R, Van Lunzen, J, Degen, O, Stellbrink, HJ, Staszewski, S, Bogner, J, Fätkenheuer, G, Kosmidis, J, Gargalianos, P, Xylomenos, G, Perdios, J, Panos, G, Filandras, A, Karabatsaki, E, Sambatakou, H, Banhegyi, D, Mulcahy, F, Yust, I, Turner, D, Burke, M, Pollack, S, Hassoun, G, Maayan, S, Vella, S, Esposito, R, Mazeu, I, Mussini, C, Arici, C, Pristera, R, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Chirianni, A, Montesarchio, E, Gargiulo, M, Antonucci, G, Iacomi, F, Narciso, P, Vlassi, C, Zaccarelli, M, Lazzarin, A, Finazzi, R & Galli, M 2011, 'A376s in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy', Journal of Infectious Diseases, vol. 204, núm. 5, pàg. 741-752. https://doi.org/10.1093/infdis/jir385

A376s in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy. / Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy et al.
In: Journal of Infectious Diseases, Vol. 204, Núm. 5, 01.09.2011, pàg. 741-752.

Producció científica: Contribució a revista › Article › Recerca › Avaluat per experts

TY - JOUR

T1 - A376s in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

AU - Paredes, Roger

AU - Puertas, Maria Carmen

AU - Bannister, Wendy

AU - Kisic, Mónica

AU - Cozzi-Lepri, Alessandro

AU - Pou, Christian

AU - Bellido, Rocío

AU - Betancor, Gilberto

AU - Bogner, Johannes

AU - Gargalianos, Panagiotis

AU - Bánhegyi, Dénes

AU - Clotet, Bonaventura

AU - Lundgren, Jens

AU - Menéndez-Arias, Luis

AU - Martinez-Picado, Javier

AU - Losso, M.

AU - Elias, C.

AU - Vetter, N.

AU - Zangerle, R.

AU - Karpov, I.

AU - Vassilenko, A.

AU - Mitsura, V. M.

AU - Suetnov, O.

AU - Clumeck, N.

AU - De Wit, S.

AU - Poll, B.

AU - Colebunders, R.

AU - Vandekerckhove, L.

AU - Hadziosmanovic, V.

AU - Kostov, K.

AU - Begovac, J.

AU - Machala, L.

AU - Rozsypal, H.

AU - Sedlacek, D.

AU - Nielsen, J.

AU - Kronborg, G.

AU - Benfield, T.

AU - Larsen, M.

AU - Gerstoft, J.

AU - Katzenstein, T.

AU - Hansen, A. B.E.

AU - Skinhøj, P.

AU - Pedersen, C.

AU - Oestergaard, L.

AU - Zilmer, K.

AU - Smidt, Jelena

AU - Ristola, M.

AU - Katlama, C.

AU - Viard, J. P.

AU - Girard, P. M.

AU - Livrozet, J. M.

AU - Vanhems, P.

AU - Pradier, C.

AU - Dabis, F.

AU - Neau, D.

AU - Rockstroh, J.

AU - Schmidt, R.

AU - Van Lunzen, J.

AU - Degen, O.

AU - Stellbrink, H. J.

AU - Staszewski, S.

AU - Bogner, J.

AU - Fätkenheuer, G.

AU - Kosmidis, J.

AU - Gargalianos, P.

AU - Xylomenos, G.

AU - Perdios, J.

AU - Panos, G.

AU - Filandras, A.

AU - Karabatsaki, E.

AU - Sambatakou, H.

AU - Banhegyi, D.

AU - Mulcahy, F.

AU - Yust, I.

AU - Turner, D.

AU - Burke, M.

AU - Pollack, S.

AU - Hassoun, G.

AU - Maayan, S.

AU - Vella, S.

AU - Esposito, R.

AU - Mazeu, I.

AU - Mussini, C.

AU - Arici, C.

AU - Pristera, R.

AU - Mazzotta, F.

AU - Gabbuti, A.

AU - Vullo, V.

AU - Lichtner, M.

AU - Chirianni, A.

AU - Montesarchio, E.

AU - Gargiulo, M.

AU - Antonucci, G.

AU - Iacomi, F.

AU - Narciso, P.

AU - Vlassi, C.

AU - Zaccarelli, M.

AU - Lazzarin, A.

AU - Finazzi, R.

AU - Galli, M.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI susceptibility of single site-directed mutants and patient-derived recombinant viruses. Enzymatic assays also determined the effects of A376S on nevirapine and template-primer binding to HIV-1 RT. Results. Virological failure occurred in 142 of 287 (49%) individuals: 77 receiving nevirapine (67%) and 65 receiving efavirenz (38%) (P < .001). Preexisting A376S was associated with an increased risk of virological failure to nevirapine (relative hazard [RH] = 10.4; 95% confidence interval [CI], 2.0-54.7), but it did not affect efavirenz outcome the same way (RH = 0.5; 95% CI, 0.1-2.2) (P value for interaction 5 .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure to nevirapine-based ART. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

AB - Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI susceptibility of single site-directed mutants and patient-derived recombinant viruses. Enzymatic assays also determined the effects of A376S on nevirapine and template-primer binding to HIV-1 RT. Results. Virological failure occurred in 142 of 287 (49%) individuals: 77 receiving nevirapine (67%) and 65 receiving efavirenz (38%) (P < .001). Preexisting A376S was associated with an increased risk of virological failure to nevirapine (relative hazard [RH] = 10.4; 95% confidence interval [CI], 2.0-54.7), but it did not affect efavirenz outcome the same way (RH = 0.5; 95% CI, 0.1-2.2) (P value for interaction 5 .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure to nevirapine-based ART. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

U2 - 10.1093/infdis/jir385

DO - 10.1093/infdis/jir385

M3 - Article

SN - 0022-1899

VL - 204

SP - 741

EP - 752

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 5

ER -

A376s in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

Resum

SDG de les Nacions Unides

Accés al document

Fingerprint

Com citar-ho