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Clin Infect Dis. 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.

Hofstra LM1,2, Sauvageot N3, Albert J4,5, Alexiev I6, Garcia F7, Struck D3, Van de Vijver DAMC8, Åsjö B9, Beshkov D6, Coughlan S10, Descamps D11, Griskevicius A12, Hamouda O13, Horban A14, Van Kasteren M15, Kolupajeva T16, Kostrikis LG17, Liitsola K18, Linka M19, Mor O20, Nielsen C21, Otelea D22, Paraskevis D23, Paredes R24, Poljak M25, Puchhammer-Stöckl E26, Sönnerborg A4,5, Staneková D27, Stanojevic M28, Van Laethem K29, Zazzi M30, Zidovec Lepej S31, Boucher CAB8, Schmit JC3, Wensing AMJ2; SPREAD Program, Puchhammer-Stockl E, Sarcletti M, Schmied B, Geit M, Balluch G, Vandamme AM, Vercauteren J, Derdelinckx I, Sasse A, Bogaert M, Ceunen H, De Roo A, De Wit S, Echahidi F, Fransen K, Goffard JC, Goubau P, Goudeseune E, Yombi JC, Lacor P, Liesnard C, Moutschen M, Pierard D, Rens R, Schrooten Y, Vaira D, Vandekerckhove LPR, 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, Lepej SZ, Begovac J, Kostrikis L, Demetriades I, Kousiappa I, Demetriou V, Hezka J, Linka M, Maly M, Machala L, Nielsen C, Jørgensen LB, Gerstoft J, Mathiesen L, Pedersen C, Nielsen H, Laursen A, Kvinesdal B, Liitsola K, Ristola M, Suni J, Sutinen J, Descamps D, Assoumou L, Castor G, Grude M, Flandre P, Storto A, 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, Zavitsanou A, Vassilakis A, Lazanas M, Chini M, Lioni A, Sakka V, Kourkounti S, Paparizos V, Antoniadou A, Papadopoulos A, Poulakou G, Katsarolis I, Protopapas K, Chryssos G, Drimis S, Gargalianos P, Xylomenos G, Lourida G, Psichogiou M, Daikos GL, Sipsas NV, Kontos A, Gamaletsou MN, Koratzanis G, Sambatakou H, Mariolis H, Skoutelis A, Papastamopoulos V, Georgiou O, Panagopoulos P, Maltezos E, Coughlan S, De Gascun C, Byrne C, Duffy M, Bergin C, Reidy D, Farrell G, Lambert J, O'Connor E, Rochford A, Low J, Coakely P, O'Dea S, Hall W, Mor O, Levi I, Chemtob D, Grossman Z, Zazzi M, de Luca A, Balotta C, Riva C, Mussini C, Caramma I, Capetti A, Colombo MC, Rossi C, Prati F, Tramuto F, Vitale F, Ciccozzi M, Angarano G, Rezza G, Kolupajeva T, Vasins O, Griskevicius A, Lipnickiene V, Schmit JC, Struck D, Sauvageot N, Hemmer R, Arendt V, Michaux C, Staub T, Sequin-Devaux C, Wensing AMJ, Boucher CAB, van de Vijver DAMC, van Kessel A, van Bentum PHM, Brinkman K, Connell BJ, van der Ende ME, Hoepelman IM, van Kasteren M, Kuipers M, Langebeek N, Richter C, Santegoets RMWJ, Schrijnders-Gudde L, Schuurman R, van de Ven BJM, Åsjö B, Kran AB, Ormaasen V, Aavitsland P, Horban A, Stanczak JJ, Stanczak GP, Firlag-Burkacka E, Wiercinska-Drapalo A, Jablonowska E, Maolepsza E, Leszczyszyn-Pynka M, Szata W, Camacho R, Palma C, Borges F, Paixão T, Duque V, Araújo F, Otelea D, Paraschiv S, Tudor AM, Cernat R, Chiriac C, Dumitrescu F, Prisecariu LJ, Stanojevic M, Jevtovic D, Salemovic D, Stanekova D, Habekova M, Chabadová Z, Drobkova T, Bukovinova P, Shunnar A, Truska P, Poljak M, Lunar M, Babic D, Tomazic J, Vidmar L, Vovko T, Karner P, Garcia F, Paredes R, Monge S, Moreno S, Del Amo J, Asensi V, Sirvent JL, de Mendoza C, Delgado R, Gutiérrez F, Berenguer J, Garcia-Bujalance S, Stella N, de Los Santos I, Blanco JR, Dalmau D, Rivero M, Segura F, Elías MJP, Alvarez M, Chueca N, Rodríguez-Martín C, Vidal C, Palomares JC, Viciana I, Viciana P, Cordoba J, Aguilera A, Domingo P, Galindo MJ, Miralles C, Del Pozo MA, Ribera E, Iribarren JA, Ruiz L, de la Torre J, Vidal F, Clotet B, Albert J, Heidarian A, Aperia-Peipke K, Axelsson M, Mild M, Karlsson A, Sönnerborg A, Thalme A, Navér L, Bratt G, Karlsson A, Blaxhult A, Gisslén M, Svennerholm B, Bergbrant I, Björkman P, Säll C, Mellgren Å, Lindholm A, Kuylenstierna N, Montelius R, Azimi F, Johansson B, Carlsson M, Johansson E, Ljungberg B, Ekvall H, Strand A, Mäkitalo S, Öberg S, Holmblad P, Höfer M, Holmberg H, Josefson P, Ryding U.

Author information

1
Luxembourg Institute of Health, Luxembourg.
2
Department of Virology, University Medical Center Utrecht, The Netherlands.
3
LuxembourgInstitute of Health, Luxembourg.
4
Karolinska Institute, Solna.
5
Karolinska University Hospital, Stockholm, Sweden.
6
National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria.
7
Complejo Hospitalario Universitario de Granada, Instituto de Investigación IBS Granada; on behalf of Cohorte de Adultos de la Red de Investigación en SIDA, Spain.
8
Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
9
University of Bergen, Norway.
10
University College Dublin, Ireland.
11
AP-HP Groupe hospitalier Bichat-Claude Bernard, IAME INSERM UMR 1137, Université Paris Diderot Sorbonne Paris Cité, Paris, France.
12
Lithuanian AIDS Center, Vilnius, Lithuania.
13
Robert Koch Institute, Berlin, Germany.
14
Hospital of Infectious Diseases, Warsaw, Poland.
15
St Elisabeth Hospital, Tilburg, The Netherlands.
16
Infectiology Center of Latvia, Riga.
17
University of Cyprus, Nicosia.
18
Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki, Finland.
19
National Reference Laboratory for HIV/AIDS, National Institute of Public Health, Prague, Czech Republic.
20
National HIV Reference Laboratory, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
21
Statens Serum Institut, Copenhagen, Denmark.
22
National Institute for Infectious Diseases "Prof. dr. Matei Bals", Bucharest, Romania.
23
National Retrovirus Reference Center, University of Athens, Greece.
24
IrsiCaixa Foundation, Badalona, Spain.
25
Faculty of Medicine, Slovenian HIV/AIDS Reference Centre, University of Ljubljana, Slovenia.
26
Medical University Vienna, Austria.
27
Slovak Medical University, Bratislava, Slovakia.
28
Faculty of Medicine, University of Belgrade, Serbia.
29
Rega Institute for Medical Research, KU Leuven, Belgium.
30
University of Siena, Italy.
31
University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia.

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

PMID:
26620652
PMCID:
PMC4741360
DOI:
10.1093/cid/civ963
[Indexed for MEDLINE]
Free PMC Article

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