Risk of severe non AIDS events is increased among patients unable to increase their CD4 + T-cell counts >200+/μl despite effective HAART

Giuseppe Lapadula, Liliane Chatenoud, Andrea Gori, Francesco Castelli, Simona Di Giambenedetto, Massimiliano Fabbiani, Franco Maggiolo, Emanuele Focà, Nicoletta Ladisa, Laura Sighinolfi, Massimo Di Pietro, Angelo Pan, Carlo Torti, G. Carosi, E. Quiros, P. Nasta, G. Paraninfo, R. Cauda, M. Colafigli, A. ScalziniF. Castelnuovo, I. El Hamad, F. Mazzotta, S. Locaputo, P. Pierotti, N. Marino, C. Blè, F. Vichi, G. Angarano, N. Ladisa, L. Monno, P. Maggi, S. Costarelli, M. Puoti, P. Viale, V. Colangeli, M. Borderi

Research output: Contribution to journalArticle

Abstract

Background: Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). Methods Patients highly-active antiretroviral therapy (HAART) with 50. Results: 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9%infectious, 17.4%renal, 17.4%cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95% CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. Conclusions: Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.

Original languageEnglish
Article numbere0124741
JournalPLoS One
Volume10
Issue number5
DOIs
Publication statusPublished - May 28 2015

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T-cells
Highly Active Antiretroviral Therapy
CD4 Lymphocyte Count
Acquired Immunodeficiency Syndrome
T-lymphocytes
T-Lymphocytes
therapeutics
death
hepatitis C
Investigational Therapies
early diagnosis
Hepatitis C
Coinfection
mixed infection
Early Diagnosis
kidneys
Kidney
incidence
liver
Liver

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Risk of severe non AIDS events is increased among patients unable to increase their CD4 + T-cell counts >200+/μl despite effective HAART. / Lapadula, Giuseppe; Chatenoud, Liliane; Gori, Andrea; Castelli, Francesco; Di Giambenedetto, Simona; Fabbiani, Massimiliano; Maggiolo, Franco; Focà, Emanuele; Ladisa, Nicoletta; Sighinolfi, Laura; Di Pietro, Massimo; Pan, Angelo; Torti, Carlo; Carosi, G.; Quiros, E.; Nasta, P.; Paraninfo, G.; Cauda, R.; Colafigli, M.; Scalzini, A.; Castelnuovo, F.; El Hamad, I.; Mazzotta, F.; Locaputo, S.; Pierotti, P.; Marino, N.; Blè, C.; Vichi, F.; Angarano, G.; Ladisa, N.; Monno, L.; Maggi, P.; Costarelli, S.; Puoti, M.; Viale, P.; Colangeli, V.; Borderi, M.

In: PLoS One, Vol. 10, No. 5, e0124741, 28.05.2015.

Research output: Contribution to journalArticle

Lapadula, G, Chatenoud, L, Gori, A, Castelli, F, Di Giambenedetto, S, Fabbiani, M, Maggiolo, F, Focà, E, Ladisa, N, Sighinolfi, L, Di Pietro, M, Pan, A, Torti, C, Carosi, G, Quiros, E, Nasta, P, Paraninfo, G, Cauda, R, Colafigli, M, Scalzini, A, Castelnuovo, F, El Hamad, I, Mazzotta, F, Locaputo, S, Pierotti, P, Marino, N, Blè, C, Vichi, F, Angarano, G, Ladisa, N, Monno, L, Maggi, P, Costarelli, S, Puoti, M, Viale, P, Colangeli, V & Borderi, M 2015, 'Risk of severe non AIDS events is increased among patients unable to increase their CD4 + T-cell counts >200+/μl despite effective HAART', PLoS One, vol. 10, no. 5, e0124741. https://doi.org/10.1371/journal.pone.0124741
Lapadula, Giuseppe ; Chatenoud, Liliane ; Gori, Andrea ; Castelli, Francesco ; Di Giambenedetto, Simona ; Fabbiani, Massimiliano ; Maggiolo, Franco ; Focà, Emanuele ; Ladisa, Nicoletta ; Sighinolfi, Laura ; Di Pietro, Massimo ; Pan, Angelo ; Torti, Carlo ; Carosi, G. ; Quiros, E. ; Nasta, P. ; Paraninfo, G. ; Cauda, R. ; Colafigli, M. ; Scalzini, A. ; Castelnuovo, F. ; El Hamad, I. ; Mazzotta, F. ; Locaputo, S. ; Pierotti, P. ; Marino, N. ; Blè, C. ; Vichi, F. ; Angarano, G. ; Ladisa, N. ; Monno, L. ; Maggi, P. ; Costarelli, S. ; Puoti, M. ; Viale, P. ; Colangeli, V. ; Borderi, M. / Risk of severe non AIDS events is increased among patients unable to increase their CD4 + T-cell counts >200+/μl despite effective HAART. In: PLoS One. 2015 ; Vol. 10, No. 5.
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title = "Risk of severe non AIDS events is increased among patients unable to increase their CD4 + T-cell counts >200+/μl despite effective HAART",
abstract = "Background: Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). Methods Patients highly-active antiretroviral therapy (HAART) with 50. Results: 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+were 77/μl (IQR: 28-142) and 56{\%} of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1{\%} of patients were INR. Thereafter, 86 nADE (30.2{\%} malignancies, 27.9{\%}infectious, 17.4{\%}renal, 17.4{\%}cardiovascular, 7{\%} hepatic) were observed, accounting for an incidence of 1.83 events (95{\%}CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95{\%}CI: 1.06-2.56). Older age (per year, HR 1.03; 95{\%}CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95{\%}CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95{\%} CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95{\%}CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. Conclusions: Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.",
author = "Giuseppe Lapadula and Liliane Chatenoud and Andrea Gori and Francesco Castelli and {Di Giambenedetto}, Simona and Massimiliano Fabbiani and Franco Maggiolo and Emanuele Foc{\`a} and Nicoletta Ladisa and Laura Sighinolfi and {Di Pietro}, Massimo and Angelo Pan and Carlo Torti and G. Carosi and E. Quiros and P. Nasta and G. Paraninfo and R. Cauda and M. Colafigli and A. Scalzini and F. Castelnuovo and {El Hamad}, I. and F. Mazzotta and S. Locaputo and P. Pierotti and N. Marino and C. Bl{\`e} and F. Vichi and G. Angarano and N. Ladisa and L. Monno and P. Maggi and S. Costarelli and M. Puoti and P. Viale and V. Colangeli and M. Borderi",
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TY - JOUR

T1 - Risk of severe non AIDS events is increased among patients unable to increase their CD4 + T-cell counts >200+/μl despite effective HAART

AU - Lapadula, Giuseppe

AU - Chatenoud, Liliane

AU - Gori, Andrea

AU - Castelli, Francesco

AU - Di Giambenedetto, Simona

AU - Fabbiani, Massimiliano

AU - Maggiolo, Franco

AU - Focà, Emanuele

AU - Ladisa, Nicoletta

AU - Sighinolfi, Laura

AU - Di Pietro, Massimo

AU - Pan, Angelo

AU - Torti, Carlo

AU - Carosi, G.

AU - Quiros, E.

AU - Nasta, P.

AU - Paraninfo, G.

AU - Cauda, R.

AU - Colafigli, M.

AU - Scalzini, A.

AU - Castelnuovo, F.

AU - El Hamad, I.

AU - Mazzotta, F.

AU - Locaputo, S.

AU - Pierotti, P.

AU - Marino, N.

AU - Blè, C.

AU - Vichi, F.

AU - Angarano, G.

AU - Ladisa, N.

AU - Monno, L.

AU - Maggi, P.

AU - Costarelli, S.

AU - Puoti, M.

AU - Viale, P.

AU - Colangeli, V.

AU - Borderi, M.

PY - 2015/5/28

Y1 - 2015/5/28

N2 - Background: Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). Methods Patients highly-active antiretroviral therapy (HAART) with 50. Results: 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9%infectious, 17.4%renal, 17.4%cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95% CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. Conclusions: Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.

AB - Background: Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). Methods Patients highly-active antiretroviral therapy (HAART) with 50. Results: 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9%infectious, 17.4%renal, 17.4%cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95% CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. Conclusions: Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.

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