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

L Marije Hofstra, Nicolas Sauvageot, Jan Albert, Ivailo Alexiev, Federico Garcia, Daniel Struck, David A M C Van de Vijver, Birgitta Åsjö, Danail Beshkov, Suzie Coughlan, Diane Descamps, Algirdas Griskevicius, Osamah Hamouda, Andrzej Horban, Marjo Van Kasteren, Tatjana Kolupajeva, Leondios G Kostrikis, Kirsi Liitsola, Marek Linka, Orna MorClaus Nielsen, Dan Otelea, Dimitrios Paraskevis, Roger Paredes, Mario Poljak, Elisabeth Puchhammer-Stöckl, Anders Sönnerborg, Danica Staneková, Maja Stanojevic, Kristel Van Laethem, Maurizio Zazzi, Snjezana Zidovec Lepej, Charles A B Boucher, Jean-Claude Schmit, Annemarie M J Wensing, SPREAD Program

Research output: Contribution to journalJournal articleResearchpeer-review

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 languageEnglish
JournalClinical Infectious Diseases
Volume62
Issue number5
Pages (from-to)655-663
ISSN1058-4838
DOIs
Publication statusPublished - 2016

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Drug Resistance
HIV
Reverse Transcriptase Inhibitors
Mutation
Rilpivirine
Protease Inhibitors
Pharmaceutical Preparations
Public Health
Guidelines
Confidence Intervals

Cite this

Hofstra, L. M., Sauvageot, N., Albert, J., Alexiev, I., Garcia, F., Struck, D., ... SPREAD Program (2016). Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe. Clinical Infectious Diseases, 62(5), 655-663. https://doi.org/10.1093/cid/civ963
Hofstra, L Marije ; Sauvageot, Nicolas ; Albert, Jan ; Alexiev, Ivailo ; Garcia, Federico ; Struck, Daniel ; Van de Vijver, David A M C ; Åsjö, Birgitta ; Beshkov, Danail ; Coughlan, Suzie ; Descamps, Diane ; Griskevicius, Algirdas ; Hamouda, Osamah ; Horban, Andrzej ; Van Kasteren, Marjo ; Kolupajeva, Tatjana ; Kostrikis, Leondios G ; Liitsola, Kirsi ; Linka, Marek ; Mor, Orna ; Nielsen, Claus ; Otelea, Dan ; Paraskevis, Dimitrios ; Paredes, Roger ; Poljak, Mario ; Puchhammer-Stöckl, Elisabeth ; Sönnerborg, Anders ; Staneková, Danica ; Stanojevic, Maja ; Van Laethem, Kristel ; Zazzi, Maurizio ; Zidovec Lepej, Snjezana ; Boucher, Charles A B ; Schmit, Jean-Claude ; Wensing, Annemarie M J ; SPREAD Program. / Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe. In: Clinical Infectious Diseases. 2016 ; Vol. 62, No. 5. pp. 655-663.
@article{9d5b89acf9864ecd81ca8a63a02fe020,
title = "Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe",
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.",
author = "Hofstra, {L Marije} and Nicolas Sauvageot and Jan Albert and Ivailo Alexiev and Federico Garcia and Daniel Struck and {Van de Vijver}, {David A M C} and Birgitta {\AA}sj{\"o} and Danail Beshkov and Suzie Coughlan and Diane Descamps and Algirdas Griskevicius and Osamah Hamouda and Andrzej Horban and {Van Kasteren}, Marjo and Tatjana Kolupajeva and Kostrikis, {Leondios G} and Kirsi Liitsola and Marek Linka and Orna Mor and Claus Nielsen and Dan Otelea and Dimitrios Paraskevis and Roger Paredes and Mario Poljak and Elisabeth Puchhammer-St{\"o}ckl and Anders S{\"o}nnerborg and Danica Stanekov{\'a} and Maja Stanojevic and {Van Laethem}, Kristel and Maurizio Zazzi and {Zidovec Lepej}, Snjezana and Boucher, {Charles A B} and Jean-Claude Schmit and Wensing, {Annemarie M J} and {SPREAD Program} and Court Pedersen",
note = "{\circledC} The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.",
year = "2016",
doi = "10.1093/cid/civ963",
language = "English",
volume = "62",
pages = "655--663",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
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Hofstra, LM, Sauvageot, N, Albert, J, Alexiev, I, Garcia, F, Struck, D, Van de Vijver, DAMC, Åsjö, B, Beshkov, D, Coughlan, S, Descamps, D, Griskevicius, A, Hamouda, O, Horban, A, Van Kasteren, M, Kolupajeva, T, Kostrikis, LG, Liitsola, K, Linka, M, Mor, O, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Staneková, D, Stanojevic, M, Van Laethem, K, Zazzi, M, Zidovec Lepej, S, Boucher, CAB, Schmit, J-C, Wensing, AMJ & SPREAD Program 2016, 'Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe', Clinical Infectious Diseases, vol. 62, no. 5, pp. 655-663. https://doi.org/10.1093/cid/civ963

Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe. / Hofstra, L Marije; Sauvageot, Nicolas; Albert, Jan; Alexiev, Ivailo; Garcia, Federico; Struck, Daniel; Van de Vijver, David A M C; Åsjö, Birgitta; Beshkov, Danail; Coughlan, Suzie; Descamps, Diane; Griskevicius, Algirdas; Hamouda, Osamah; Horban, Andrzej; Van Kasteren, Marjo; Kolupajeva, Tatjana; Kostrikis, Leondios G; Liitsola, Kirsi; Linka, Marek; Mor, Orna; Nielsen, Claus; Otelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Staneková, Danica; Stanojevic, Maja; Van Laethem, Kristel; Zazzi, Maurizio; Zidovec Lepej, Snjezana; Boucher, Charles A B; Schmit, Jean-Claude; Wensing, Annemarie M J; SPREAD Program.

In: Clinical Infectious Diseases, Vol. 62, No. 5, 2016, p. 655-663.

Research output: Contribution to journalJournal articleResearchpeer-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, Leondios 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 - Zidovec Lepej, Snjezana

AU - Boucher, Charles A B

AU - Schmit, Jean-Claude

AU - Wensing, Annemarie M J

AU - SPREAD Program

AU - Pedersen, Court

N1 - © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

PY - 2016

Y1 - 2016

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.

U2 - 10.1093/cid/civ963

DO - 10.1093/cid/civ963

M3 - Journal article

C2 - 26620652

VL - 62

SP - 655

EP - 663

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 5

ER -