Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

Dominique Costagliola; Bruno Ledergerber; Carlo Torti; Ard van Sighem; Daniel Podzamczer; Amanda Mocroft; Maria Dorrucci; Bernard Masquelier; Andrea de Luca; Klaus Jansen; Stephane De Wit; Niels Obel; Gerd F�tkenheuer; Giota Touloumi; Cristina Mussini; Antonella Castagna; Cristoph Stephan; Federico Garc�a; Robert Zangerle; Xavier Duval; Santiago Perez-Hoyos; Laurence Meyer; Jade Ghosn; C�line Fabre-Colin; Jesper Kjaer; Genevieve Ch�ne; Jesper Grarup; Andrew Phillips; Rebecca Lodwick; Carlo Torti; Maria Dorrucci; Huldrych F G�nthard; Claudia Michalik; George Chrysos; Antonella Castagna; Pursuing Later Treatment Option II (PLATO II) Project Team of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE)

doi:10.1093/infdis/jis752

Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

Dominique Costagliola, Bruno Ledergerber, Carlo Torti, Ard van Sighem, Daniel Podzamczer, Amanda Mocroft, Maria Dorrucci, Bernard Masquelier, Andrea de Luca, Klaus Jansen, Stephane De Wit, Niels Obel, Gerd F�tkenheuer, Giota Touloumi, Cristina Mussini, Antonella Castagna, Cristoph Stephan, Federico Garc�a, Robert Zangerle, Xavier DuvalSantiago Perez-Hoyos, Laurence Meyer, Jade Ghosn, C�line Fabre-Colin, Jesper Kjaer, Genevieve Ch�ne, Jesper Grarup, Andrew Phillips, Rebecca Lodwick, Carlo Torti, Maria Dorrucci, Huldrych F G�nthard, Claudia Michalik, George Chrysos, Antonella Castagna, Pursuing Later Treatment Option II (PLATO II) Project Team of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE)

Abstract

Background. Low CD4⁺ T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4⁺ T-cell counts after triple-class virological failure.Methods. We included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4⁺ T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations.Results. The analyses included 2424 individuals with a total of 23 922 CD4⁺ T-cell count measurements. In adjusted models (excluding current viral load and year), CD4⁺ T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/μL [95% confidence interval {CI}, 3.9-41]; P =. 017) or drugs from the new classes (increase, 39 cells/μL [95% CI, 15-62]; P =. 001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of <2.5 log₁₀ copies/mL, levels of 2.5-3.5, 3.5-4.5, 4.5-5.5, and >5.5 log₁₀ copies/mL were associated with CD4⁺ T-cell count decreases of 51, 84, 137, and 186 cells/μL, respectively (P <. 001).Conclusions. The approximately linear inverse relationship between log₁₀ viral load and CD4⁺ T-cell count indicates that there are likely immunologic benefits from lowering viral load even by modest amounts that do not lead to undetectable viral loads. This is important for patients with low CD4⁺ T-cell counts and few drug options.

Original language	English
Journal	The Journal of Infectious Diseases
Volume	207
Issue number	5
Pages (from-to)	759-67
Number of pages	9
ISSN	0022-1899
DOIs	https://doi.org/10.1093/infdis/jis752
Publication status	Published - 1 Mar 2013

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Costagliola, D., Ledergerber, B., Torti, C., van Sighem, A., Podzamczer, D., Mocroft, A., Dorrucci, M., Masquelier, B., de Luca, A., Jansen, K., De Wit, S., Obel, N., F�tkenheuer, G., Touloumi, G., Mussini, C., Castagna, A., Stephan, C., Garc�a, F., Zangerle, R., ... (COHERE), P. L. T. O. II. P. T. O. T. C. O. O. HIV. E. R. E. (2013). Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes. The Journal of Infectious Diseases, 207(5), 759-67. https://doi.org/10.1093/infdis/jis752

Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes. / Costagliola, Dominique; Ledergerber, Bruno; Torti, Carlo et al.

In: The Journal of Infectious Diseases, Vol. 207, No. 5, 01.03.2013, p. 759-67.

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

Costagliola, D, Ledergerber, B, Torti, C, van Sighem, A, Podzamczer, D, Mocroft, A, Dorrucci, M, Masquelier, B, de Luca, A, Jansen, K, De Wit, S, Obel, N, F�tkenheuer, G, Touloumi, G, Mussini, C, Castagna, A, Stephan, C, Garc�a, F, Zangerle, R, Duval, X, Perez-Hoyos, S, Meyer, L, Ghosn, J, Fabre-Colin, C, Kjaer, J, Ch�ne, G, Grarup, J, Phillips, A, Lodwick, R, Torti, C, Dorrucci, M, G�nthard, HF, Michalik, C, Chrysos, G, Castagna, A & (COHERE), PLTOIIPTOTCOOHIVERE 2013, 'Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes', The Journal of Infectious Diseases, vol. 207, no. 5, pp. 759-67. https://doi.org/10.1093/infdis/jis752

@article{56b677b129cd4b5486b657a4d9160c7c,

title = "Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes",

abstract = "Background. Low CD4+ T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4+ T-cell counts after triple-class virological failure.Methods. We included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4+ T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations.Results. The analyses included 2424 individuals with a total of 23 922 CD4+ T-cell count measurements. In adjusted models (excluding current viral load and year), CD4+ T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/μL [95% confidence interval {CI}, 3.9-41]; P =. 017) or drugs from the new classes (increase, 39 cells/μL [95% CI, 15-62]; P =. 001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of <2.5 log10 copies/mL, levels of 2.5-3.5, 3.5-4.5, 4.5-5.5, and >5.5 log10 copies/mL were associated with CD4+ T-cell count decreases of 51, 84, 137, and 186 cells/μL, respectively (P <. 001).Conclusions. The approximately linear inverse relationship between log10 viral load and CD4+ T-cell count indicates that there are likely immunologic benefits from lowering viral load even by modest amounts that do not lead to undetectable viral loads. This is important for patients with low CD4+ T-cell counts and few drug options.",

author = "Dominique Costagliola and Bruno Ledergerber and Carlo Torti and {van Sighem}, Ard and Daniel Podzamczer and Amanda Mocroft and Maria Dorrucci and Bernard Masquelier and {de Luca}, Andrea and Klaus Jansen and {De Wit}, Stephane and Niels Obel and Gerd F�tkenheuer and Giota Touloumi and Cristina Mussini and Antonella Castagna and Cristoph Stephan and Federico Garc�a and Robert Zangerle and Xavier Duval and Santiago Perez-Hoyos and Laurence Meyer and Jade Ghosn and C�line Fabre-Colin and Jesper Kjaer and Genevieve Ch�ne and Jesper Grarup and Andrew Phillips and Rebecca Lodwick and Carlo Torti and Maria Dorrucci and G�nthard, {Huldrych F} and Claudia Michalik and George Chrysos and Antonella Castagna and (COHERE), {Pursuing Later Treatment Option II (PLATO II) Project Team of the Collaboration of Observational HIV Epidemiological Research Europe}",

year = "2013",

month = mar,

day = "1",

doi = "10.1093/infdis/jis752",

language = "English",

volume = "207",

pages = "759--67",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

AU - Costagliola, Dominique

AU - Ledergerber, Bruno

AU - Torti, Carlo

AU - van Sighem, Ard

AU - Podzamczer, Daniel

AU - Mocroft, Amanda

AU - Dorrucci, Maria

AU - Masquelier, Bernard

AU - de Luca, Andrea

AU - Jansen, Klaus

AU - De Wit, Stephane

AU - Obel, Niels

AU - F�tkenheuer, Gerd

AU - Touloumi, Giota

AU - Mussini, Cristina

AU - Castagna, Antonella

AU - Stephan, Cristoph

AU - Garc�a, Federico

AU - Zangerle, Robert

AU - Duval, Xavier

AU - Perez-Hoyos, Santiago

AU - Meyer, Laurence

AU - Ghosn, Jade

AU - Fabre-Colin, C�line

AU - Kjaer, Jesper

AU - Ch�ne, Genevieve

AU - Grarup, Jesper

AU - Phillips, Andrew

AU - Lodwick, Rebecca

AU - Torti, Carlo

AU - Dorrucci, Maria

AU - G�nthard, Huldrych F

AU - Michalik, Claudia

AU - Chrysos, George

AU - Castagna, Antonella

AU - (COHERE), Pursuing Later Treatment Option II (PLATO II) Project Team of the Collaboration of Observational HIV Epidemiological Research Europe

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Background. Low CD4+ T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4+ T-cell counts after triple-class virological failure.Methods. We included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4+ T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations.Results. The analyses included 2424 individuals with a total of 23 922 CD4+ T-cell count measurements. In adjusted models (excluding current viral load and year), CD4+ T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/μL [95% confidence interval {CI}, 3.9-41]; P =. 017) or drugs from the new classes (increase, 39 cells/μL [95% CI, 15-62]; P =. 001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of <2.5 log10 copies/mL, levels of 2.5-3.5, 3.5-4.5, 4.5-5.5, and >5.5 log10 copies/mL were associated with CD4+ T-cell count decreases of 51, 84, 137, and 186 cells/μL, respectively (P <. 001).Conclusions. The approximately linear inverse relationship between log10 viral load and CD4+ T-cell count indicates that there are likely immunologic benefits from lowering viral load even by modest amounts that do not lead to undetectable viral loads. This is important for patients with low CD4+ T-cell counts and few drug options.

AB - Background. Low CD4+ T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4+ T-cell counts after triple-class virological failure.Methods. We included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4+ T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations.Results. The analyses included 2424 individuals with a total of 23 922 CD4+ T-cell count measurements. In adjusted models (excluding current viral load and year), CD4+ T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/μL [95% confidence interval {CI}, 3.9-41]; P =. 017) or drugs from the new classes (increase, 39 cells/μL [95% CI, 15-62]; P =. 001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of <2.5 log10 copies/mL, levels of 2.5-3.5, 3.5-4.5, 4.5-5.5, and >5.5 log10 copies/mL were associated with CD4+ T-cell count decreases of 51, 84, 137, and 186 cells/μL, respectively (P <. 001).Conclusions. The approximately linear inverse relationship between log10 viral load and CD4+ T-cell count indicates that there are likely immunologic benefits from lowering viral load even by modest amounts that do not lead to undetectable viral loads. This is important for patients with low CD4+ T-cell counts and few drug options.

U2 - 10.1093/infdis/jis752

DO - 10.1093/infdis/jis752

M3 - Journal article

C2 - 23225900

SN - 0022-1899

VL - 207

SP - 759

EP - 767

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 5

ER -

Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

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