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. 2016 Mar 1;62(5):655-663.
doi: 10.1093/cid/civ963. Epub 2015 Nov 29.

Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

L Marije Hofstra  1   2 , Nicolas Sauvageot  3 , Jan Albert  4   5 , Ivailo Alexiev  6 , Federico Garcia  7 , Daniel Struck  3 , David A M C Van de Vijver  8 , Birgitta Åsjö  9 , Danail Beshkov  6 , Suzie Coughlan  10 , Diane Descamps  11 , Algirdas Griskevicius  12 , Osamah Hamouda  13 , Andrzej Horban  14 , Marjo Van Kasteren  15 , Tatjana Kolupajeva  16 , Leondios G Kostrikis  17 , Kirsi Liitsola  18 , Marek Linka  19 , Orna Mor  20 , Claus Nielsen  21 , Dan Otelea  22 , Dimitrios Paraskevis  23 , Roger Paredes  24 , Mario Poljak  25 , Elisabeth Puchhammer-Stöckl  26 , Anders Sönnerborg  4   5 , Danica Staneková  27 , Maja Stanojevic  28 , Kristel Van Laethem  29 , Maurizio Zazzi  30 , Snjezana Zidovec Lepej  31 , Charles A B Boucher  8 , Jean-Claude Schmit  3 , Annemarie M J Wensing  2 ; SPREAD Program; E Puchhammer-Stockl, M Sarcletti, B Schmied, M Geit, G Balluch, A-M Vandamme, J Vercauteren, I Derdelinckx, A Sasse, M Bogaert, H Ceunen, A De Roo, S De Wit, F Echahidi, K Fransen, J-C Goffard, P Goubau, E Goudeseune, J-C Yombi, P Lacor, C Liesnard, M Moutschen, D Pierard, R Rens, Y Schrooten, D Vaira, L P R Vandekerckhove, A Van den Heuvel, B Van Der Gucht, M Van Ranst, E Van Wijngaerden, B Vandercam, M Vekemans, C Verhofstede, N Clumeck, K Van Laethem, D Beshkov, I Alexiev, S Zidovec Lepej, J Begovac, L Kostrikis, I Demetriades, I Kousiappa, V Demetriou, J Hezka, M Linka, M Maly, L Machala, C Nielsen, L B Jørgensen, J Gerstoft, L Mathiesen, C Pedersen, H Nielsen, A Laursen, B Kvinesdal, K Liitsola, M Ristola, J Suni, J Sutinen, D Descamps, L Assoumou, G Castor, M Grude, P Flandre, A Storto, O Hamouda, C Kücherer, T Berg, P Braun, G Poggensee, M Däumer, J Eberle, H Heiken, R Kaiser, H Knechten, K Korn, H Müller, S Neifer, B Schmidt, H Walter, B Gunsenheimer-Bartmeyer, T Harrer, D Paraskevis, A Hatzakis, A Zavitsanou, A Vassilakis, M Lazanas, M Chini, A Lioni, V Sakka, S Kourkounti, V Paparizos, A Antoniadou, A Papadopoulos, G Poulakou, I Katsarolis, K Protopapas, G Chryssos, S Drimis, P Gargalianos, G Xylomenos, G Lourida, M Psichogiou, G L Daikos, N V Sipsas, A Kontos, M N Gamaletsou, G Koratzanis, H Sambatakou, H Mariolis, A Skoutelis, V Papastamopoulos, O Georgiou, P Panagopoulos, E Maltezos, S Coughlan, C De Gascun, C Byrne, M Duffy, C Bergin, D Reidy, G Farrell, J Lambert, E O'Connor, A Rochford, J Low, P Coakely, S O'Dea, W Hall, O Mor, I Levi, D Chemtob, Z Grossman, M Zazzi, A de Luca, C Balotta, C Riva, C Mussini, I Caramma, A Capetti, M C Colombo, C Rossi, F Prati, F Tramuto, F Vitale, M Ciccozzi, G Angarano, G Rezza, T Kolupajeva, O Vasins, A Griskevicius, V Lipnickiene, J C Schmit, D Struck, N Sauvageot, R Hemmer, V Arendt, C Michaux, T Staub, C Sequin-Devaux, A M J Wensing, C A B Boucher, D A M C van de Vijver, A van Kessel, P H M van Bentum, K Brinkman, B J Connell, M E van der Ende, I M Hoepelman, M van Kasteren, M Kuipers, N Langebeek, C Richter, R M W J Santegoets, L Schrijnders-Gudde, R Schuurman, B J M van de Ven, B Åsjö, A-M Bakken Kran, V Ormaasen, P Aavitsland, A Horban, J J Stanczak, G P Stanczak, E Firlag-Burkacka, A Wiercinska-Drapalo, E Jablonowska, E Maolepsza, M Leszczyszyn-Pynka, W Szata, R Camacho, C Palma, F Borges, T Paixão, V Duque, F Araújo, D Otelea, S Paraschiv, A M Tudor, R Cernat, C Chiriac, F Dumitrescu, L J Prisecariu, M Stanojevic, Dj Jevtovic, D Salemovic, D Stanekova, M Habekova, Z Chabadová, T Drobkova, P Bukovinova, A Shunnar, P Truska, M Poljak, M Lunar, D Babic, J Tomazic, L Vidmar, T Vovko, P Karner, F Garcia, R Paredes, S Monge, S Moreno, J Del Amo, V Asensi, J L Sirvent, C de Mendoza, R Delgado, F Gutiérrez, J Berenguer, S Garcia-Bujalance, N Stella, I de Los Santos, J R Blanco, D Dalmau, M Rivero, F Segura, M J Pérez Elías, M Alvarez, N Chueca, C Rodríguez-Martín, C Vidal, J C Palomares, I Viciana, P Viciana, J Cordoba, A Aguilera, P Domingo, M J Galindo, C Miralles, M A Del Pozo, E Ribera, J A Iribarren, L Ruiz, J de la Torre, F Vidal, B Clotet, J Albert, A Heidarian, K Aperia-Peipke, M Axelsson, M Mild, A Karlsson, A Sönnerborg, A Thalme, L Navér, G Bratt, A Karlsson, A Blaxhult, M Gisslén, B Svennerholm, I Bergbrant, P Björkman, C Säll, Å Mellgren, A Lindholm, N Kuylenstierna, R Montelius, F Azimi, B Johansson, M Carlsson, E Johansson, B Ljungberg, H Ekvall, A Strand, S Mäkitalo, S Öberg, P Holmblad, M Höfer, H Holmberg, P Josefson, U Ryding
Affiliations

Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

L Marije Hofstra et al. Clin Infect Dis. .

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.

Keywords: Europe; HIV-1; antiretroviral therapy; drug resistance; transmission.

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Figures

Figure 1.
Figure 1.
Overall weighted prevalence of transmitted drug resistance in patients with newly diagnosed human immunodeficiency virus (HIV) in Europe. The error bars indicate the standard error. Abbreviations: NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; TDR, transmitted drug resistance.
Figure 2.
Figure 2.
Prevalence of transmitted drug resistance (TDR) among different transmission risk groups (men who have sex with men [MSM], heterosexuals [HSX], and injecting drug users [IDUs]) and subtypes, for nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs).
Figure 3.
Figure 3.
Predicted efficacy to antiretroviral compounds of patients in Europe newly diagnosed with human immunodeficiency virus in 2008–2010. Abbreviations: 3TC, lamivudine; ABC, abacavir; ATV, atazanavir; AZT, zidovudine; D4T, stavudine; DRV, darunavir; EFV, efavirenz; ETR, etravirine; FPV, fosamprenavir; FTC, emtricitabine; IDV, indinavir; LPV, lopinavir; NFV, nelfinavir; NVP, nevirapine; RPV, rilpivirine; SQV, saquinavir; TDF, tenofovir; TPV, tipranavir.
Figure 4.
Figure 4.
Genotypic sensitivity scores (GSSs) of 8 recommended first-line regimens in patients in Europe newly diagnosed with human immunodeficiency virus in 2008–2010. Abbreviations: ATV, atazanavir; DRV, darunavir; EFV, efavirenz; KVX, Kivexa (abacavir + lamivudine); NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RPV, rilpivirine; TVD, Truvada (tenofovir +emtricitabine).
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