Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings

Alessandro Cozzi-Lepri; Andrew N Phillips; Javier Martinez-Picado; Antonella d'Arminio Monforte; Christine Katlama; Ann-Brit Eg Hansen; Andrzej Horban; Johann Bruun; Bonaventura Clotet; Jens Lundgren; Eurosida Study Group

doi:10.1086/604731

Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings

Alessandro Cozzi-Lepri, Andrew N Phillips, Javier Martinez-Picado, Antonella d'Arminio Monforte, Christine Katlama, Ann-Brit Eg Hansen, Andrzej Horban, Johann Bruun, Bonaventura Clotet, Jens Lundgren, Eurosida Study Group

Department of Immunology and Microbiology

43 Citations (Scopus)

Abstract

BACKGROUND: Because changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs). METHODS: The study included patients in EuroSIDA with 2 available genotypic resistance tests (GRTs) (human immunodeficiency virus [HIV] RNA level, >500 copies/mL in any measure between tests), provided that the first GRT was performed after the first virological failure of a TA and that the same TA was continued until the second GRT. RESULTS: At the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95% confidence interval, 3.7-5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual (vs homosexual) contacts were associated with a faster rate of TAM accumulation. CONCLUSIONS: Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in RLSs.

Original language	English
Journal	Journal of Infectious Diseases
Volume	200
Issue number	5
Pages (from-to)	687-97
Number of pages	10
ISSN	0022-1899
DOIs	https://doi.org/10.1086/604731 https://doi.org/10.1086/604731
Publication status	Published - 2009

UN SDGs

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

Access to Document

Fingerprint

Dive into the research topics of 'Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings'. Together they form a unique fingerprint.

Cite this

Cozzi-Lepri, A., Phillips, A. N., Martinez-Picado, J., Monforte, A. DA., Katlama, C., Eg Hansen, A-B., Horban, A., Bruun, J., Clotet, B., Lundgren, J., & Eurosida Study Group (2009). Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings. Journal of Infectious Diseases, 200(5), 687-97. https://doi.org/10.1086/604731, https://doi.org/10.1086/604731

Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings. / Cozzi-Lepri, Alessandro; Phillips, Andrew N; Martinez-Picado, Javier et al.

In: Journal of Infectious Diseases, Vol. 200, No. 5, 2009, p. 687-97.

Research output: Contribution to journal › Journal article › Research › peer-review

Cozzi-Lepri, A, Phillips, AN, Martinez-Picado, J, Monforte, ADA, Katlama, C, Eg Hansen, A-B, Horban, A, Bruun, J, Clotet, B, Lundgren, J & Eurosida Study Group 2009, 'Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings', Journal of Infectious Diseases, vol. 200, no. 5, pp. 687-97. https://doi.org/10.1086/604731, https://doi.org/10.1086/604731

Cozzi-Lepri A, Phillips AN, Martinez-Picado J, Monforte ADA, Katlama C, Eg Hansen A-B et al. Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings. Journal of Infectious Diseases. 2009;200(5):687-97. doi: 10.1086/604731, http://dx.doi.org/10.1086/604731

Cozzi-Lepri, Alessandro ; Phillips, Andrew N ; Martinez-Picado, Javier et al. / Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings. In: Journal of Infectious Diseases. 2009 ; Vol. 200, No. 5. pp. 687-97.

@article{1f08b5905c1411df928f000ea68e967b,

title = "Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings",

abstract = "BACKGROUND: Because changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs). METHODS: The study included patients in EuroSIDA with 2 available genotypic resistance tests (GRTs) (human immunodeficiency virus [HIV] RNA level, >500 copies/mL in any measure between tests), provided that the first GRT was performed after the first virological failure of a TA and that the same TA was continued until the second GRT. RESULTS: At the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95% confidence interval, 3.7-5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual (vs homosexual) contacts were associated with a faster rate of TAM accumulation. CONCLUSIONS: Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in RLSs.",

author = "Alessandro Cozzi-Lepri and Phillips, {Andrew N} and Javier Martinez-Picado and Monforte, {Antonella d'Arminio} and Christine Katlama and {Eg Hansen}, Ann-Brit and Andrzej Horban and Johann Bruun and Bonaventura Clotet and Jens Lundgren and {Eurosida Study Group}",

note = "Keywords: Adolescent; Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Drug Resistance, Viral; Female; HIV; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutation, Missense; Stavudine; Young Adult; Zidovudine",

year = "2009",

doi = "10.1086/604731",

language = "English",

volume = "200",

pages = "687--97",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings

AU - Cozzi-Lepri, Alessandro

AU - Phillips, Andrew N

AU - Martinez-Picado, Javier

AU - Monforte, Antonella d'Arminio

AU - Katlama, Christine

AU - Eg Hansen, Ann-Brit

AU - Horban, Andrzej

AU - Bruun, Johann

AU - Clotet, Bonaventura

AU - Lundgren, Jens

AU - Eurosida Study Group

N1 - Keywords: Adolescent; Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Drug Resistance, Viral; Female; HIV; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutation, Missense; Stavudine; Young Adult; Zidovudine

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Because changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs). METHODS: The study included patients in EuroSIDA with 2 available genotypic resistance tests (GRTs) (human immunodeficiency virus [HIV] RNA level, >500 copies/mL in any measure between tests), provided that the first GRT was performed after the first virological failure of a TA and that the same TA was continued until the second GRT. RESULTS: At the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95% confidence interval, 3.7-5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual (vs homosexual) contacts were associated with a faster rate of TAM accumulation. CONCLUSIONS: Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in RLSs.

AB - BACKGROUND: Because changes in antiretroviral therapy in resource-limited settings (RLSs) are delayed until patients experience immunological or clinical failure, it is important to be able to estimate the consequences in terms of accumulation of thymidine analogue (TA) mutations (TAMs). METHODS: The study included patients in EuroSIDA with 2 available genotypic resistance tests (GRTs) (human immunodeficiency virus [HIV] RNA level, >500 copies/mL in any measure between tests), provided that the first GRT was performed after the first virological failure of a TA and that the same TA was continued until the second GRT. RESULTS: At the time of the first GRT in a pair (t0), 1 year after virological failure, a median of 3 TAMs were detected, mutations 41L and 215Y in 65% of pairs and 67N in 52%. Overall, 126 TAMs were accumulated during 548 person-years of follow-up (PYFUs) (1/4.3 years; 95% confidence interval, 3.7-5.0 years). Greater predicted activity of the TA at t0, TAM profile 2 (TAM2; vs TAM profile 1 [TAM1]) profiles at t0, use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) at t0 (vs combined NNRTI and protease inhibitor), and acquisition of HIV infection through heterosexual (vs homosexual) contacts were associated with a faster rate of TAM accumulation. CONCLUSIONS: Although the estimated rate of TAM accumulation was lower than anticipated, all possible efforts should be continued to increase the availability of drug options in RLSs.

U2 - 10.1086/604731

DO - 10.1086/604731

M3 - Journal article

C2 - 19604043

SN - 0022-1899

VL - 200

SP - 687

EP - 697

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 5

ER -