Abstract
Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.
| Original language | English |
|---|---|
| Pages (from-to) | 655-663 |
| Number of pages | 9 |
| Journal | Clinical Infectious Diseases |
| Volume | 62 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 29 Nov 2016 |
Keywords
- Antiretroviral therapy
- Drug resistance
- Europe
- HIV-1
- Transmission
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In: Clinical Infectious Diseases, Vol. 62, No. 5, 29.11.2016, p. 655-663.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe
AU - Hofstra, L. Marije
AU - Sauvageot, Nicolas
AU - Albert, Jan
AU - Alexiev, Ivailo
AU - Garcia, Federico
AU - Struck, Daniel
AU - Van De Vijver, David A M C
AU - Åsjö, Birgitta
AU - Beshkov, Danail
AU - Coughlan, Suzie
AU - Descamps, Diane
AU - Griskevicius, Algirdas
AU - Hamouda, Osamah
AU - Horban, Andrzej
AU - Van Kasteren, Marjo
AU - Kolupajeva, Tatjana
AU - Kostrikis, Leontios G.
AU - Liitsola, Kirsi
AU - Linka, Marek
AU - Mor, Orna
AU - Nielsen, Claus
AU - Otelea, Dan
AU - Paraskevis, Dimitrios
AU - Paredes, Roger
AU - Poljak, Mario
AU - Puchhammer-Stöckl, Elisabeth
AU - Sönnerborg, Anders
AU - Staneková, Danica
AU - Stanojevic, Maja
AU - Van Laethem, Kristel
AU - Zazzi, Maurizio
AU - Lepej, Snjezana Zidovec
AU - Boucher, Charles A B
AU - Schmit, Jean Claude
AU - Wensing, Annemarie M J
AU - Puchhammer-Stockl, E.
AU - Sarcletti, M.
AU - Schmied, B.
AU - Geit, M.
AU - Balluch, G.
AU - Vandamme, A. M.
AU - Vercauteren, J.
AU - Derdelinckx, I.
AU - Sasse, A.
AU - Bogaert, M.
AU - Ceunen, H.
AU - De Roo, A.
AU - De Wit, S.
AU - Echahidi, F.
AU - Fransen, K.
AU - Goffard, J. C.
AU - Goubau, P.
AU - Goudeseune, E.
AU - Yombi, J. C.
AU - Lacor, P.
AU - Liesnard, C.
AU - Moutschen, M.
AU - Pierard, D.
AU - Rens, R.
AU - Schrooten, Y.
AU - Vaira, D.
AU - Vandekerckhove, L. P R
AU - Van Den Heuvel, A.
AU - Van Der Gucht, B.
AU - Van Ranst, M.
AU - Van Wijngaerden, E.
AU - Vandercam, B.
AU - Vekemans, M.
AU - Verhofstede, C.
AU - Clumeck, N.
AU - Van Laethem, K.
AU - Beshkov, D.
AU - Alexiev, I.
AU - Lepej, S. Zidovec
AU - Begovac, J.
AU - Kostrikis, Leontios G.
AU - Demetriades, I.
AU - Kousiappa, I.
AU - Demetriou, V.
AU - Hezka, J.
AU - Linka, M.
AU - Maly, M.
AU - Machala, L.
AU - Nielsen, C.
AU - Jørgensen, L. B.
AU - Gerstoft, J.
AU - Mathiesen, L.
AU - Pedersen, C.
AU - Nielsen, H.
AU - Laursen, A.
AU - Kvinesdal, B.
AU - Liitsola, K.
AU - Ristola, M.
AU - Suni, J.
AU - Sutinen, J.
AU - Descamps, D.
AU - Assoumou, L.
AU - Castor, G.
AU - Grude, M.
AU - Flandre, P.
AU - Storto, A.
AU - Hamouda, O.
AU - Kücherer, C.
AU - Berg, T.
AU - Braun, P.
AU - Poggensee, G.
AU - Däumer, M.
AU - Eberle, J.
AU - Heiken, H.
AU - Kaiser, R.
AU - Knechten, H.
AU - Korn, K.
AU - Müller, H.
AU - Neifer, S.
AU - Schmidt, B.
AU - Walter, H.
AU - Gunsenheimer-Bartmeyer, B.
AU - Harrer, T.
AU - Paraskevis, D.
AU - Hatzakis, A.
AU - Zavitsanou, A.
AU - Vassilakis, A.
AU - Lazanas, M.
AU - Chini, M.
AU - Lioni, A.
AU - Sakka, V.
AU - Kourkounti, S.
AU - Paparizos, V.
AU - Antoniadou, A.
AU - Papadopoulos, A.
AU - Poulakou, G.
AU - Katsarolis, I.
AU - Protopapas, K.
AU - Chryssos, G.
AU - Drimis, S.
AU - Gargalianos, P.
AU - Xylomenos, G.
AU - Lourida, G.
AU - Psichogiou, M.
AU - Daikos, G. L.
AU - Sipsas, N. V.
AU - Kontos, A.
AU - Gamaletsou, M. N.
AU - Koratzanis, G.
AU - Sambatakou, E.
AU - Mariolis, H.
AU - Skoutelis, A.
AU - Papastamopoulos, V.
AU - Georgiou, O.
AU - Panagopoulos, P.
AU - Maltezos, E.
AU - Coughlan, S.
AU - De Gascun, C.
AU - Byrne, C.
AU - Duffy, M.
AU - Bergin, C.
AU - Reidy, D.
AU - Farrell, G.
AU - Lambert, J.
AU - O'Connor, E.
AU - Rochford, A.
AU - Low, J.
AU - Coakely, P.
AU - O'Dea, S.
AU - Hall, W.
AU - Mor, O.
AU - Levi, I.
AU - Chemtob, D.
AU - Grossman, Z.
AU - Zazzi, M.
AU - De Luca, A.
AU - Balotta, C.
AU - Riva, C.
AU - Mussini, C.
AU - Caramma, I.
AU - Capetti, A.
AU - Colombo, M. C.
AU - Rossi, C.
AU - Prati, F.
AU - Tramuto, F.
AU - Vitale, F.
AU - Ciccozzi, M.
AU - Angarano, G.
AU - Rezza, G.
AU - Kolupajeva, T.
AU - Kolupajeva, T.
AU - Vasins, O.
AU - Griskevicius, A.
AU - Lipnickiene, V.
AU - Schmit, J. C.
AU - Struck, D.
AU - Sauvageot, N.
AU - Hemmer, R.
AU - Arendt, V.
AU - Michaux, C.
AU - Staub, T.
AU - Sequin-Devaux, C.
AU - Wensing, A. M J
AU - Boucher, C. A B
AU - Van Kessel, A.
AU - Van Bentum, P. H M
AU - Brinkman, K.
AU - Connell, B. J.
AU - Van Der Ende, M. E.
AU - Hoepelman, I. M.
AU - Van Kasteren, M.
AU - Kuipers, M.
AU - Langebeek, N.
AU - Richter, C.
AU - Santegoets, R. M W J
AU - Schrijnders-Gudde, L.
AU - Schuurman, R.
AU - Van De Ven, B. J M
AU - Åsjö, B.
AU - Kran, A. M Bakken
AU - Ormaasen, V.
AU - Aavitsland, P.
AU - Horban, A.
AU - Stanczak, J. J.
AU - Stanczak, G. P.
AU - Firlag-Burkacka, E.
AU - Wiercinska-Drapalo, A.
AU - Jablonowska, E.
AU - Maolepsza, E.
AU - Leszczyszyn-Pynka, M.
AU - Szata, W.
AU - Camacho, R.
AU - Palma, C.
AU - Borges, F.
AU - Paixão, T.
AU - Duque, V.
AU - Araújo, F.
AU - Otelea, D.
AU - Paraschiv, S.
AU - Tudor, A. M.
AU - Cernat, R.
AU - Chiriac, C.
AU - Dumitrescu, F.
AU - Prisecariu, L. J.
AU - Stanojevic, M.
AU - Jevtovic, Dj
AU - Salemovic, D.
AU - Stanekova, D.
AU - Habekova, M.
AU - Chabadová, Z.
AU - Drobkova, T.
AU - Bukovinova, P.
AU - Shunnar, A.
AU - Truska, P.
AU - Poljak, M.
AU - Lunar, M.
AU - Babic, D.
AU - Tomazic, J.
AU - Vidmar, L.
AU - Vovko, T.
AU - Karner, P.
AU - Garcia, F.
AU - Paredes, R.
AU - Monge, S.
AU - Moreno, S.
AU - Del Amo, J.
AU - Asensi, V.
AU - Sirvent, J. L.
AU - De Mendoza, C.
AU - Delgado, R.
AU - Gutiérrez, F.
AU - Berenguer, J.
AU - Garcia-Bujalance, S.
AU - Stella, N.
AU - De Los Santos, I.
AU - Blanco, J. R.
AU - Dalmau, D.
AU - Rivero, M.
AU - Segura, F.
AU - Elías, M. J Pérez
AU - Alvarez, M.
AU - Chueca, N.
AU - Rodríguez-Martín, C.
AU - Vidal, C.
AU - Palomares, J. C.
AU - Viciana, I.
AU - Viciana, P.
AU - Cordoba, J.
AU - Aguilera, A.
AU - Domingo, P.
AU - Galindo, M. J.
AU - Miralles, C.
AU - Del Pozo, M. A.
AU - Ribera, E.
AU - Iribarren, J. A.
AU - Ruiz, L.
AU - De La Torre, J.
AU - Vidal, F.
AU - Clotet, B.
AU - Albert, J.
AU - Heidarian, A.
AU - Aperia-Peipke, K.
AU - Axelsson, M.
AU - Mild, M.
AU - Karlsson, A.
AU - Sönnerborg, A.
AU - Thalme, A.
AU - Navér, L.
AU - Bratt, G.
AU - Karlsson, A.
AU - Blaxhult, A.
AU - Gisslén, M.
AU - Svennerholm, B.
AU - Bergbrant, I.
AU - Björkman, P.
AU - Säll, C.
AU - Mellgren,
AU - Lindholm, A.
AU - Kuylenstierna, N.
AU - Montelius, R.
AU - Azimi, F.
AU - Johansson, B.
AU - Carlsson, M.
AU - Johansson, E.
AU - Ljungberg, B.
AU - Ekvall, H.
AU - Strand, A.
AU - Mäkitalo, S.
AU - Öberg, S.
AU - Holmblad, P.
AU - Höfer, M.
AU - Holmberg, H.
AU - Josefson, P.
AU - Ryding, U.
PY - 2016/11/29
Y1 - 2016/11/29
N2 - Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.
AB - Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.
KW - Antiretroviral therapy
KW - Drug resistance
KW - Europe
KW - HIV-1
KW - Transmission
UR - http://www.scopus.com/inward/record.url?scp=84960114637&partnerID=8YFLogxK
U2 - 10.1093/cid/civ963
DO - 10.1093/cid/civ963
M3 - Article
C2 - 26620652
AN - SCOPUS:84960114637
SN - 1058-4838
VL - 62
SP - 655
EP - 663
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 5
ER -