Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

Alessandro Cozzi-Lepri; Andrew N Phillips; Lidia Ruiz; Bonaventura Clotet; Clive Loveday; Jesper Kjaer; Helene Mens; Nathan Clumeck; Ludmila Viksna; Francisco Antunes; Ladislav Machala; Jens D Lundgren; Eurosida Study Group

doi:10.1097/QAD.0b013e3280141fdf

Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

Alessandro Cozzi-Lepri, Andrew N Phillips, Lidia Ruiz, Bonaventura Clotet, Clive Loveday, Jesper Kjaer, Helene Mens, Nathan Clumeck, Ludmila Viksna, Francisco Antunes, Ladislav Machala, Jens D Lundgren, Eurosida Study Group

81 Citations (Scopus)

Abstract

OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.

Original language	English
Journal	AIDS
Volume	21
Issue number	6
Pages (from-to)	721-32
Number of pages	11
ISSN	0269-9370
DOIs	https://doi.org/10.1097/QAD.0b013e3280141fdf https://doi.org/10.1097/QAD.0b013e3280141fdf
Publication status	Published - 2007

Keywords

Adult
Aged
Amino Acids
Anti-HIV Agents
Anti-Retroviral Agents
CD4 Lymphocyte Count
Drug Resistance, Viral
Drug Therapy, Combination
Female
Genotype
HIV Infections
HIV Protease Inhibitors
HIV-1
Humans
Male
Middle Aged
Mutation
Reverse Transcriptase Inhibitors
Risk Assessment
Treatment Failure
Viral Load

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cozzi-Lepri, A., Phillips, A. N., Ruiz, L., Clotet, B., Loveday, C., Kjaer, J., Mens, H., Clumeck, N., Viksna, L., Antunes, F., Machala, L., Lundgren, J. D., & Eurosida Study Group (2007). Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen. AIDS, 21(6), 721-32. https://doi.org/10.1097/QAD.0b013e3280141fdf, https://doi.org/10.1097/QAD.0b013e3280141fdf

Cozzi-Lepri, A, Phillips, AN, Ruiz, L, Clotet, B, Loveday, C, Kjaer, J, Mens, H, Clumeck, N, Viksna, L, Antunes, F, Machala, L, Lundgren, JD & Eurosida Study Group 2007, 'Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen', AIDS, vol. 21, no. 6, pp. 721-32. https://doi.org/10.1097/QAD.0b013e3280141fdf, https://doi.org/10.1097/QAD.0b013e3280141fdf

@article{12a61d7020ec11ddbc23000ea68e967b,

title = "Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen",

abstract = "OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.",

keywords = "Adult, Aged, Amino Acids, Anti-HIV Agents, Anti-Retroviral Agents, CD4 Lymphocyte Count, Drug Resistance, Viral, Drug Therapy, Combination, Female, Genotype, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Male, Middle Aged, Mutation, Reverse Transcriptase Inhibitors, Risk Assessment, Treatment Failure, Viral Load",

author = "Alessandro Cozzi-Lepri and Phillips, {Andrew N} and Lidia Ruiz and Bonaventura Clotet and Clive Loveday and Jesper Kjaer and Helene Mens and Nathan Clumeck and Ludmila Viksna and Francisco Antunes and Ladislav Machala and Lundgren, {Jens D} and {Eurosida Study Group}",

year = "2007",

doi = "10.1097/QAD.0b013e3280141fdf",

language = "English",

volume = "21",

pages = "721--32",

journal = "AIDS, Supplement",

issn = "1350-2840",

publisher = "Lippincott Williams & Wilkins",

number = "6",

}

TY - JOUR

T1 - Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

AU - Cozzi-Lepri, Alessandro

AU - Phillips, Andrew N

AU - Ruiz, Lidia

AU - Clotet, Bonaventura

AU - Loveday, Clive

AU - Kjaer, Jesper

AU - Mens, Helene

AU - Clumeck, Nathan

AU - Viksna, Ludmila

AU - Antunes, Francisco

AU - Machala, Ladislav

AU - Lundgren, Jens D

AU - Eurosida Study Group

PY - 2007

Y1 - 2007

N2 - OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.

AB - OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.

KW - Adult

KW - Aged

KW - Amino Acids

KW - Anti-HIV Agents

KW - Anti-Retroviral Agents

KW - CD4 Lymphocyte Count

KW - Drug Resistance, Viral

KW - Drug Therapy, Combination

KW - Female

KW - Genotype

KW - HIV Infections

KW - HIV Protease Inhibitors

KW - HIV-1

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Reverse Transcriptase Inhibitors

KW - Risk Assessment

KW - Treatment Failure

KW - Viral Load

U2 - 10.1097/QAD.0b013e3280141fdf

DO - 10.1097/QAD.0b013e3280141fdf

M3 - Journal article

C2 - 17413693

SN - 1350-2840

VL - 21

SP - 721

EP - 732

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 6

ER -

Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

Abstract

Keywords

UN SDGs

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