Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy

Cozzi Lepri Alesandro; David Dunn; Deenan Pillay; Caroline A. Sabin; Esther Fearnhill; Anna Maria Gerettsabini; Teresa Hill; Steve Kaye; Loveleen Bansi; Erasmus Smit; Margaret Johnson; Sheila Burns; Richard Gilson; Sheila Cameron; Philippa Easterbrook; Mark Zuckerman; Brian Gazzard; John Walsh; Martin Fisher; Chloe Orkin; Jonathan Ainsworth; Clifford Leen; Mark Gompels; Jane Anderson; Andrew N. Phillips; Abdel Babiker; Kholoud Porter; Tariq Sadiq; Achim Schwenk; Nicky Mackie; Alan Winston; Valerie Delpech; David Asboe; Anton Pozniak; Patricia Cane; Porton Down; Duncan Churchill; Duncan Clark; Linda Lazarus; Hannah Green; Paul Kellam; David Goldberg; Antony Hale; Svilen Konov; Andrew Leigh-Brown; Nicola Mackie; Peter Tilston; Ian Williams; Hongyi Zhang; Adam Glabay

doi:10.1086/651684

Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy

Cozzi Lepri Alesandro^*, David Dunn, Deenan Pillay, Caroline A. Sabin, Esther Fearnhill, Anna Maria Gerettsabini, Teresa Hill, Steve Kaye, Loveleen Bansi, Erasmus Smit, Margaret Johnson, Sheila Burns, Richard Gilson, Sheila Cameron, Philippa Easterbrook, Mark Zuckerman, Brian Gazzard, John Walsh, Martin Fisher, Chloe OrkinJonathan Ainsworth, Clifford Leen, Mark Gompels, Jane Anderson, Andrew N. Phillips, Abdel Babiker, Kholoud Porter, Tariq Sadiq, Achim Schwenk, Nicky Mackie, Alan Winston, Valerie Delpech, David Asboe, Anton Pozniak, Patricia Cane, Porton Down, Duncan Churchill, Duncan Clark, Linda Lazarus, Hannah Green, Paul Kellam, David Goldberg, Antony Hale, Svilen Konov, Andrew Leigh-Brown, Nicola Mackie, Peter Tilston, Ian Williams, Hongyi Zhang, Adam Glabay

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background. Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice. Methods. We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance. Results. Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, ≥ 1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, ≥ 1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and ≥ 1 major PIIAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a Pl/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P = .98). Conclusions. In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen.

Original language	English
Pages (from-to)	1275-1285
Number of pages	11
Journal	Clinical Infectious Diseases
Volume	50
Issue number	9
DOIs	https://doi.org/10.1086/651684
Publication status	Published - 1 May 2010

Bibliographical note

Funding Information:
Financial support. The UK HIV Drug Resistance Database is partly funded by the Department of Health; additional support is provided by Bristol-Myers Squibb, Gilead, Pfizer, and Tibotec (a division of Janssen-Cilag Ltd). This project was supported by the European AIDS Treatment Network (NEAT; European Commission NEAT contract FP6/03757). Potential conflicts of interest. All authors: no conflicts.

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10.1086/651684

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Alesandro, C. L., Dunn, D., Pillay, D., Sabin, C. A., Fearnhill, E., Gerettsabini, A. M., Hill, T., Kaye, S., Bansi, L., Smit, E., Johnson, M., Burns, S., Gilson, R., Cameron, S., Easterbrook, P., Zuckerman, M., Gazzard, B., Walsh, J., Fisher, M., ... Glabay, A. (2010). Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy. Clinical Infectious Diseases, 50(9), 1275-1285. https://doi.org/10.1086/651684

@article{e78bc24047dc491688679ac53699a41a,

title = "Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy",

abstract = "Background. Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice. Methods. We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance. Results. Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, ≥ 1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, ≥ 1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and ≥ 1 major PIIAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a Pl/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P = .98). Conclusions. In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen.",

author = "Alesandro, {Cozzi Lepri} and David Dunn and Deenan Pillay and Sabin, {Caroline A.} and Esther Fearnhill and Gerettsabini, {Anna Maria} and Teresa Hill and Steve Kaye and Loveleen Bansi and Erasmus Smit and Margaret Johnson and Sheila Burns and Richard Gilson and Sheila Cameron and Philippa Easterbrook and Mark Zuckerman and Brian Gazzard and John Walsh and Martin Fisher and Chloe Orkin and Jonathan Ainsworth and Clifford Leen and Mark Gompels and Jane Anderson and Phillips, {Andrew N.} and Abdel Babiker and Kholoud Porter and Tariq Sadiq and Achim Schwenk and Nicky Mackie and Alan Winston and Valerie Delpech and David Asboe and Anton Pozniak and Patricia Cane and Porton Down and Duncan Churchill and Duncan Clark and Linda Lazarus and Hannah Green and Paul Kellam and David Goldberg and Antony Hale and Svilen Konov and Andrew Leigh-Brown and Nicola Mackie and Peter Tilston and Ian Williams and Hongyi Zhang and Adam Glabay",

note = "Funding Information: Financial support. The UK HIV Drug Resistance Database is partly funded by the Department of Health; additional support is provided by Bristol-Myers Squibb, Gilead, Pfizer, and Tibotec (a division of Janssen-Cilag Ltd). This project was supported by the European AIDS Treatment Network (NEAT; European Commission NEAT contract FP6/03757). Potential conflicts of interest. All authors: no conflicts.",

year = "2010",

month = may,

day = "1",

doi = "10.1086/651684",

language = "English",

volume = "50",

pages = "1275--1285",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "9",

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Alesandro, CL, Dunn, D, Pillay, D, Sabin, CA, Fearnhill, E, Gerettsabini, AM, Hill, T, Kaye, S, Bansi, L, Smit, E, Johnson, M, Burns, S, Gilson, R, Cameron, S, Easterbrook, P, Zuckerman, M, Gazzard, B, Walsh, J, Fisher, M, Orkin, C, Ainsworth, J, Leen, C, Gompels, M, Anderson, J, Phillips, AN, Babiker, A, Porter, K, Sadiq, T, Schwenk, A, Mackie, N, Winston, A, Delpech, V, Asboe, D, Pozniak, A, Cane, P, Down, P, Churchill, D, Clark, D, Lazarus, L, Green, H, Kellam, P, Goldberg, D, Hale, A, Konov, S, Leigh-Brown, A, Mackie, N, Tilston, P, Williams, I, Zhang, H & Glabay, A 2010, 'Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy', Clinical Infectious Diseases, vol. 50, no. 9, pp. 1275-1285. https://doi.org/10.1086/651684

TY - JOUR

T1 - Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy

AU - Alesandro, Cozzi Lepri

AU - Dunn, David

AU - Pillay, Deenan

AU - Sabin, Caroline A.

AU - Fearnhill, Esther

AU - Gerettsabini, Anna Maria

AU - Hill, Teresa

AU - Kaye, Steve

AU - Bansi, Loveleen

AU - Smit, Erasmus

AU - Johnson, Margaret

AU - Burns, Sheila

AU - Gilson, Richard

AU - Cameron, Sheila

AU - Easterbrook, Philippa

AU - Zuckerman, Mark

AU - Gazzard, Brian

AU - Walsh, John

AU - Fisher, Martin

AU - Orkin, Chloe

AU - Ainsworth, Jonathan

AU - Leen, Clifford

AU - Gompels, Mark

AU - Anderson, Jane

AU - Phillips, Andrew N.

AU - Babiker, Abdel

AU - Porter, Kholoud

AU - Sadiq, Tariq

AU - Schwenk, Achim

AU - Mackie, Nicky

AU - Winston, Alan

AU - Delpech, Valerie

AU - Asboe, David

AU - Pozniak, Anton

AU - Cane, Patricia

AU - Down, Porton

AU - Churchill, Duncan

AU - Clark, Duncan

AU - Lazarus, Linda

AU - Green, Hannah

AU - Kellam, Paul

AU - Goldberg, David

AU - Hale, Antony

AU - Konov, Svilen

AU - Leigh-Brown, Andrew

AU - Mackie, Nicola

AU - Tilston, Peter

AU - Williams, Ian

AU - Zhang, Hongyi

AU - Glabay, Adam

N1 - Funding Information: Financial support. The UK HIV Drug Resistance Database is partly funded by the Department of Health; additional support is provided by Bristol-Myers Squibb, Gilead, Pfizer, and Tibotec (a division of Janssen-Cilag Ltd). This project was supported by the European AIDS Treatment Network (NEAT; European Commission NEAT contract FP6/03757). Potential conflicts of interest. All authors: no conflicts.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Background. Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice. Methods. We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance. Results. Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, ≥ 1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, ≥ 1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and ≥ 1 major PIIAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a Pl/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P = .98). Conclusions. In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen.

AB - Background. Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice. Methods. We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance. Results. Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, ≥ 1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, ≥ 1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and ≥ 1 major PIIAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a Pl/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P = .98). Conclusions. In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen.

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U2 - 10.1086/651684

DO - 10.1086/651684

M3 - Article

C2 - 20353366

AN - SCOPUS:77951006096

VL - 50

SP - 1275

EP - 1285

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 9

ER -

Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy

Abstract

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