Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure.

Nicolai Lohse; Louise B Jørgensen; Gitte Kronborg; Axel Møller; Birgit Kvinesdal; Henrik T Sørensen; Niels Obel; Jan Gerstoft; NN NN

Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure.

Nicolai Lohse, Louise B Jørgensen, Gitte Kronborg, Axel Møller, Birgit Kvinesdal, Henrik T Sørensen, Niels Obel, Jan Gerstoft, NN NN

Department of Clinical Medicine

24 Citations (Scopus)

Abstract

OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.

Original language	English
Journal	Antiviral Therapy
Volume	12
Issue number	6
Pages (from-to)	909-17
Number of pages	8
ISSN	1359-6535
Publication status	Published - 2007

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http://www.intmedpress.com/Journal%20Management/article.cfm?viewinfo=3742183F520F092C300C585C1440162639441102041865101E443F745167173009060058060068320D5E7062060F111D5E073D541479286B00453F00174500014F25450E054401252149004F085313555166

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Lohse, N., Jørgensen, L. B., Kronborg, G., Møller, A., Kvinesdal, B., Sørensen, H. T., Obel, N., Gerstoft, J., & NN, NN. (2007). Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure. Antiviral Therapy, 12(6), 909-17. http://www.intmedpress.com/Journal%20Management/article.cfm?viewinfo=3742183F520F092C300C585C1440162639441102041865101E443F745167173009060058060068320D5E7062060F111D5E073D541479286B00453F00174500014F25450E054401252149004F085313555166

Lohse, N, Jørgensen, LB, Kronborg, G, Møller, A, Kvinesdal, B, Sørensen, HT, Obel, N, Gerstoft, J & NN, NN 2007, 'Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure.', Antiviral Therapy, vol. 12, no. 6, pp. 909-17. <http://www.intmedpress.com/Journal%20Management/article.cfm?viewinfo=3742183F520F092C300C585C1440162639441102041865101E443F745167173009060058060068320D5E7062060F111D5E073D541479286B00453F00174500014F25450E054401252149004F085313555166>

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title = "Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure.",

abstract = "OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.",

author = "Nicolai Lohse and J{\o}rgensen, {Louise B} and Gitte Kronborg and Axel M{\o}ller and Birgit Kvinesdal and S{\o}rensen, {Henrik T} and Niels Obel and Jan Gerstoft and NN NN",

year = "2007",

language = "English",

volume = "12",

pages = "909--17",

journal = "Antiviral Therapy",

issn = "1359-6535",

publisher = "International Medical Press",

number = "6",

}

TY - JOUR

T1 - Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure.

AU - Lohse, Nicolai

AU - Jørgensen, Louise B

AU - Kronborg, Gitte

AU - Møller, Axel

AU - Kvinesdal, Birgit

AU - Sørensen, Henrik T

AU - Obel, Niels

AU - Gerstoft, Jan

AU - NN, NN

PY - 2007

Y1 - 2007

N2 - OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.

AB - OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk of death according to the number of mutations and individual mutations was estimated by Cox regression analysis and adjusted for potential confounders. RESULTS: Resistance tests were done for 133 of the 179 patients who experienced TCF. The median number of resistance mutations was eight (interquartile range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus < or =8 mutations was associated with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic resistance mutations and specific single mutations predicted mortality.

M3 - Journal article

SN - 1359-6535

VL - 12

SP - 909

EP - 917

JO - Antiviral Therapy

JF - Antiviral Therapy

IS - 6

ER -

Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure.

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