Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe

on behalf of EuroSIDA in EuroCoord

doi:10.1371/journal.pone.0087160

Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe

on behalf of EuroSIDA in EuroCoord

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

Background: The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. Methods: Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/ml and viral load (VL).500 copies/mL were followed-up from the first day of VL<=50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. Results:2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p=0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p=0.361). Conclusion: Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.

Original language	English
Article number	e87160
Journal	PLOS ONE
Volume	9
Issue	1
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0087160
Publication status	Published - 31 Jan 2014

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@article{68bf1bb2c9e9499d96c0859b59b95555,

title = "Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe",

abstract = "Background: The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. Methods: Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/ml and viral load (VL).500 copies/mL were followed-up from the first day of VL<=50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. Results:2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p=0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p=0.361). Conclusion: Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.",

author = "Alexander Zoufaly and Alessandro Cozzi-Lepri and Joanne Reekie and Ole Kirk and Jens Lundgren and Peter Reiss and Djordje Jevtovic and L. Machala and Robert Zangerle and Amanda Mocroft and {Van Lunzen}, Jan and M. Losso and M. Kundro and N. Vetter and I. Karpov and A. Vassilenko and Mitsura, {V. M.} and O. Suetnov and N. Clumeck and {De Wit}, S. and M. Delforge and R. Colebunders and L. Vandekerckhove and V. Hadziosmanovic and K. Kostov and J. Begovac and L. Machala and D. Jilich and D. Sedlacek and J. Nielsen and G. Kronborg and T. Benfield and M. Larsen and J. Gerstoft and T. Katzenstein and Hansen, {A. B.E.} and C. Pedersen and L. Ostergaard and R. Schmidt and J. Bruun and F. Antunes and M. Gutierrez and R. Weber and Johnson, {A. M.} and Johnson, {M. A.} and J. Weber and J. Kj{\ae}r and L. Peters and Fischer, {A. H.} and J. Kj{\ae}r and {on behalf of EuroSIDA in EuroCoord}",

year = "2014",

month = jan,

day = "31",

doi = "10.1371/journal.pone.0087160",

language = "English",

volume = "9",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "1",

}

TY - JOUR

T1 - Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe

AU - Zoufaly, Alexander

AU - Cozzi-Lepri, Alessandro

AU - Reekie, Joanne

AU - Kirk, Ole

AU - Lundgren, Jens

AU - Reiss, Peter

AU - Jevtovic, Djordje

AU - Machala, L.

AU - Zangerle, Robert

AU - Mocroft, Amanda

AU - Van Lunzen, Jan

AU - Losso, M.

AU - Kundro, M.

AU - Vetter, N.

AU - Karpov, I.

AU - Vassilenko, A.

AU - Mitsura, V. M.

AU - Suetnov, O.

AU - Clumeck, N.

AU - De Wit, S.

AU - Delforge, M.

AU - Colebunders, R.

AU - Vandekerckhove, L.

AU - Hadziosmanovic, V.

AU - Kostov, K.

AU - Begovac, J.

AU - Machala, L.

AU - Jilich, D.

AU - Sedlacek, D.

AU - Nielsen, J.

AU - Kronborg, G.

AU - Benfield, T.

AU - Larsen, M.

AU - Gerstoft, J.

AU - Katzenstein, T.

AU - Hansen, A. B.E.

AU - Pedersen, C.

AU - Ostergaard, L.

AU - Schmidt, R.

AU - Bruun, J.

AU - Antunes, F.

AU - Gutierrez, M.

AU - Weber, R.

AU - Johnson, A. M.

AU - Johnson, M. A.

AU - Weber, J.

AU - Kjær, J.

AU - Peters, L.

AU - Fischer, A. H.

AU - Kjær, J.

AU - on behalf of EuroSIDA in EuroCoord

PY - 2014/1/31

Y1 - 2014/1/31

N2 - Background: The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. Methods: Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/ml and viral load (VL).500 copies/mL were followed-up from the first day of VL<=50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. Results:2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p=0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p=0.361). Conclusion: Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.

AB - Background: The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. Methods: Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/ml and viral load (VL).500 copies/mL were followed-up from the first day of VL<=50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. Results:2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p=0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p=0.361). Conclusion: Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.

UR - http://www.scopus.com/inward/record.url?scp=84900323491&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0087160

DO - 10.1371/journal.pone.0087160

M3 - Journal article

C2 - 24498036

AN - SCOPUS:84900323491

SN - 1932-6203

VL - 9

JO - PLOS ONE

JF - PLOS ONE

IS - 1

M1 - e87160

ER -

Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe

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