Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

Wendy P Bannister; Lidia Ruiz; Alessandro Cozzi-Lepri; Amanda Mocroft; Ole Kirk; Schlomo Staszewski; Clive Loveday; Anders Karlsson; Antonella d'Arminio Monforte; Bonaventura Clotet; Jens Lundgren; Eurosida Study Group

doi:10.1097/QAD.0b013e3282f3cc35

Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

Wendy P Bannister, Lidia Ruiz, Alessandro Cozzi-Lepri, Amanda Mocroft, Ole Kirk, Schlomo Staszewski, Clive Loveday, Anders Karlsson, Antonella d'Arminio Monforte, Bonaventura Clotet, Jens Lundgren, Eurosida Study Group

40 Citations (Scopus)

Abstract

OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) with genotypic resistance test results available at time of initiation (baseline). Virological failure was defined as two consecutive values > 500 copies/ml after starting the regimen. Cox models were used to investigate time to virological failure (the first of two values). RESULTS: A total of 759 patients were included (13% antiretroviral-naive): 389 initiated NVP and 370 initiated EFV. Baseline IAS-USA NNRTI resistance mutations were detected in 3%. Using the Rega algorithm (version 7.1) to interpret resistance, 460 (64%) patients had resistance (full or intermediate) to at least one drug they were starting (69% NVP, 60% EFV, P = 0.011); 287 (74%) NVP and 168 (45%) EFV patients experienced virological failure after treatment initiation, P < 0.001. After adjustment for previous antiretroviral use, previous AIDS, year started NNRTI, CD4 cell count (baseline, nadir), viral load (baseline, maximum), and baseline drug resistance (measured by Rega), the relative hazards (EFV versus NVP) of virological failure was 0.50, 95% confidence interval: 0.39-0.65, P < 0.001. At time of virological failure, comparable levels of NNRTI resistance were detected. The K103N mutation emerged more in patients failing EFV and Y181C in patients failing NVP. CONCLUSIONS: NVP may be associated with an inferior virological outcome compared to EFV in NNRTI-naive patients with extensive resistance to other drug classes. The profile of NNRTI resistance mutations when virologically failing an NNRTI-containing regimen appears to depend on the NNRTI the patients fail.

Original language	English
Journal	AIDS
Volume	22
Issue number	3
Pages (from-to)	367-76
Number of pages	9
ISSN	0269-9370
DOIs	https://doi.org/10.1097/QAD.0b013e3282f3cc35
Publication status	Published - 2008

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10.1097/QAD.0b013e3282f3cc35

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Bannister, W. P., Ruiz, L., Cozzi-Lepri, A., Mocroft, A., Kirk, O., Staszewski, S., Loveday, C., Karlsson, A., Monforte, A. DA., Clotet, B., Lundgren, J., & Eurosida Study Group (2008). Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA. AIDS, 22(3), 367-76. https://doi.org/10.1097/QAD.0b013e3282f3cc35

Bannister, WP, Ruiz, L, Cozzi-Lepri, A, Mocroft, A, Kirk, O, Staszewski, S, Loveday, C, Karlsson, A, Monforte, ADA, Clotet, B, Lundgren, J & Eurosida Study Group 2008, 'Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA', AIDS, vol. 22, no. 3, pp. 367-76. https://doi.org/10.1097/QAD.0b013e3282f3cc35

@article{837ae130ff3911ddb219000ea68e967b,

title = "Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA",

abstract = "OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) with genotypic resistance test results available at time of initiation (baseline). Virological failure was defined as two consecutive values > 500 copies/ml after starting the regimen. Cox models were used to investigate time to virological failure (the first of two values). RESULTS: A total of 759 patients were included (13% antiretroviral-naive): 389 initiated NVP and 370 initiated EFV. Baseline IAS-USA NNRTI resistance mutations were detected in 3%. Using the Rega algorithm (version 7.1) to interpret resistance, 460 (64%) patients had resistance (full or intermediate) to at least one drug they were starting (69% NVP, 60% EFV, P = 0.011); 287 (74%) NVP and 168 (45%) EFV patients experienced virological failure after treatment initiation, P < 0.001. After adjustment for previous antiretroviral use, previous AIDS, year started NNRTI, CD4 cell count (baseline, nadir), viral load (baseline, maximum), and baseline drug resistance (measured by Rega), the relative hazards (EFV versus NVP) of virological failure was 0.50, 95% confidence interval: 0.39-0.65, P < 0.001. At time of virological failure, comparable levels of NNRTI resistance were detected. The K103N mutation emerged more in patients failing EFV and Y181C in patients failing NVP. CONCLUSIONS: NVP may be associated with an inferior virological outcome compared to EFV in NNRTI-naive patients with extensive resistance to other drug classes. The profile of NNRTI resistance mutations when virologically failing an NNRTI-containing regimen appears to depend on the NNRTI the patients fail.",

author = "Bannister, {Wendy P} and Lidia Ruiz and Alessandro Cozzi-Lepri and Amanda Mocroft and Ole Kirk and Schlomo Staszewski and Clive Loveday and Anders Karlsson and Monforte, {Antonella d'Arminio} and Bonaventura Clotet and Jens Lundgren and {Eurosida Study Group}",

note = "Keywords: Adult; Anti-HIV Agents; Benzoxazines; Cohort Studies; Drug Resistance, Viral; Europe; Female; Genotype; HIV Infections; HIV-1; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Nevirapine; Proportional Hazards Models; Reverse Transcriptase Inhibitors; Treatment Failure; Treatment Outcome",

year = "2008",

doi = "10.1097/QAD.0b013e3282f3cc35",

language = "English",

volume = "22",

pages = "367--76",

journal = "AIDS, Supplement",

issn = "1350-2840",

publisher = "Lippincott Williams & Wilkins",

number = "3",

}

TY - JOUR

T1 - Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

AU - Bannister, Wendy P

AU - Ruiz, Lidia

AU - Cozzi-Lepri, Alessandro

AU - Mocroft, Amanda

AU - Kirk, Ole

AU - Staszewski, Schlomo

AU - Loveday, Clive

AU - Karlsson, Anders

AU - Monforte, Antonella d'Arminio

AU - Clotet, Bonaventura

AU - Lundgren, Jens

AU - Eurosida Study Group

N1 - Keywords: Adult; Anti-HIV Agents; Benzoxazines; Cohort Studies; Drug Resistance, Viral; Europe; Female; Genotype; HIV Infections; HIV-1; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutation; Nevirapine; Proportional Hazards Models; Reverse Transcriptase Inhibitors; Treatment Failure; Treatment Outcome

PY - 2008

Y1 - 2008

N2 - OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) with genotypic resistance test results available at time of initiation (baseline). Virological failure was defined as two consecutive values > 500 copies/ml after starting the regimen. Cox models were used to investigate time to virological failure (the first of two values). RESULTS: A total of 759 patients were included (13% antiretroviral-naive): 389 initiated NVP and 370 initiated EFV. Baseline IAS-USA NNRTI resistance mutations were detected in 3%. Using the Rega algorithm (version 7.1) to interpret resistance, 460 (64%) patients had resistance (full or intermediate) to at least one drug they were starting (69% NVP, 60% EFV, P = 0.011); 287 (74%) NVP and 168 (45%) EFV patients experienced virological failure after treatment initiation, P < 0.001. After adjustment for previous antiretroviral use, previous AIDS, year started NNRTI, CD4 cell count (baseline, nadir), viral load (baseline, maximum), and baseline drug resistance (measured by Rega), the relative hazards (EFV versus NVP) of virological failure was 0.50, 95% confidence interval: 0.39-0.65, P < 0.001. At time of virological failure, comparable levels of NNRTI resistance were detected. The K103N mutation emerged more in patients failing EFV and Y181C in patients failing NVP. CONCLUSIONS: NVP may be associated with an inferior virological outcome compared to EFV in NNRTI-naive patients with extensive resistance to other drug classes. The profile of NNRTI resistance mutations when virologically failing an NNRTI-containing regimen appears to depend on the NNRTI the patients fail.

AB - OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) with genotypic resistance test results available at time of initiation (baseline). Virological failure was defined as two consecutive values > 500 copies/ml after starting the regimen. Cox models were used to investigate time to virological failure (the first of two values). RESULTS: A total of 759 patients were included (13% antiretroviral-naive): 389 initiated NVP and 370 initiated EFV. Baseline IAS-USA NNRTI resistance mutations were detected in 3%. Using the Rega algorithm (version 7.1) to interpret resistance, 460 (64%) patients had resistance (full or intermediate) to at least one drug they were starting (69% NVP, 60% EFV, P = 0.011); 287 (74%) NVP and 168 (45%) EFV patients experienced virological failure after treatment initiation, P < 0.001. After adjustment for previous antiretroviral use, previous AIDS, year started NNRTI, CD4 cell count (baseline, nadir), viral load (baseline, maximum), and baseline drug resistance (measured by Rega), the relative hazards (EFV versus NVP) of virological failure was 0.50, 95% confidence interval: 0.39-0.65, P < 0.001. At time of virological failure, comparable levels of NNRTI resistance were detected. The K103N mutation emerged more in patients failing EFV and Y181C in patients failing NVP. CONCLUSIONS: NVP may be associated with an inferior virological outcome compared to EFV in NNRTI-naive patients with extensive resistance to other drug classes. The profile of NNRTI resistance mutations when virologically failing an NNRTI-containing regimen appears to depend on the NNRTI the patients fail.

U2 - 10.1097/QAD.0b013e3282f3cc35

DO - 10.1097/QAD.0b013e3282f3cc35

M3 - Journal article

C2 - 18195563

SN - 1350-2840

VL - 22

SP - 367

EP - 376

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 3

ER -

Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

Abstract

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