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; Leontios G. Kostrikis; Kirsi Liitsola; Marek Linka; Orna Mor; Claus 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; 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; SPREAD Program

doi:10.1093/cid/civ963

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, Leontios 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^*, 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, SPREAD Program

^*Corresponding author for this work

Infection and Immunotherapy Research

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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	https://doi.org/10.1093/cid/civ963
Publication status	Published - 1 Mar 2016

Keywords

Antiretroviral therapy
Drug resistance
Europe
HIV-1
Transmission

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10.1093/cid/civ963

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Hofstra, L. M., Sauvageot, N., Albert, J., Alexiev, I., Garcia, F., Struck, D., Van De Vijver, D. A. M. C., Åsjö, B., Beshkov, D., Coughlan, S., Descamps, D., Griskevicius, A., Hamouda, O., Horban, A., Van Kasteren, M., Kolupajeva, T., Kostrikis, L. G., Liitsola, K., Linka, M., ... 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

@article{50655f26ca1848959f8b8d6858f707ec,

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.",

keywords = "Antiretroviral therapy, Drug resistance, Europe, HIV-1, Transmission",

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, {Leontios 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 Lepej, {Snjezana Zidovec} and Boucher, {Charles A.B.} and Schmit, {Jean Claude} and Wensing, {Annemarie M.J.} and E. Puchhammer-Stockl and M. Sarcletti and B. Schmied and M. Geit and G. Balluch and Vandamme, {A. M.} and J. Vercauteren and I. Derdelinckx and A. Sasse and M. Bogaert and H. Ceunen and {De Roo}, A. and {De Wit}, S. and F. Echahidi and K. Fransen and {SPREAD Program}",

note = "Publisher Copyright: {\textcopyright} The Author 2015.",

year = "2016",

month = mar,

day = "1",

doi = "10.1093/cid/civ963",

language = "English",

volume = "62",

pages = "655--663",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "5",

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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, Lepej, SZ, Boucher, CAB, Schmit, JC, Wensing, AMJ, 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 & 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

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 - SPREAD Program

PY - 2016/3/1

Y1 - 2016/3/1

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 -

Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

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