Predictors of long-term immunological outcome in rebounding patients on protease inhibitor-based HAART after initial successful virologic suppression: Implications for timing to switch

Lina Rachele Tomasoni, Andrea Patroni, Carlo Torti, Giuseppe Paraninfo, Franco Gargiulo, Eugenia Quiros-Roldan, Maria Cristina Uccelli, Paolo Airò, Carmine Tinelli, Giampero Carosi, Francesco Castelli, S. Casari, A. Pan, M. Airoldi, C. Fausti, I. El Hamad, F. Moretti, C. Pezzoli, R. Poni Gore, A. BeltrameP. Nasta, L. Scudeller

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: To assess predictive factors of long-term immune restoration in patients who started protease inhibitor (PI)-based HAART and experienced virological rebound after initial complete success. Method: A retrospective longitudinal analysis of all HIV-infected patients who started their first PI-based HAART and reached viral load below 500 copies/mL was carried out in a large academic center in Italy. Patients were classified either as complete virologic responder (CR) or rebounders (REB) when confirmed plasma viremia was detected thereafter. Immunological outcome was the area under the curve (AUC) of the absolute CD4+ cell count change since the 8th month after treatment initiation (CD4+ T-cell AUC). Association between baseline characteristics, virological outcome, and CD4+T-cell AUC was assessed by univariate and multivariate analysis. Results: There were 374 patients who were included in the study. Mean follow-up was 30.2 months. There were 226/374 patients (60.4%) who remained CR while 148/374 (39.6%) presented at least one rebound (REB). Among REB patients, complete viral suppression was regained in 15/42 (35.7%) and 50/106 (47.1%) patients who underwent therapy changes or not, respectively. When multiple linear regression was carried out, previous nucleoside reverse transcriptase inhibitor (NRTI) experience and baseline CD4+ cell count below 350 cells/μL did not impair long-term immune restoration. The occurrence of rebound, its duration (>18 months), and its magnitude (peak of viral load > 10,000 copies/mL) were independent negative prognostic factors. Conclusion: The occurrence of viral rebound is independently associated with significantly impaired long-term immunological restoration. The magnitude of viral rebound (<10,000 copies/mL) and its duration (<18 months) may be useful to identify those rebounding patients who may still profit from maintaining the current failing therapy if a more aggressive approach may be expected to be deleterious for tolerability reasons or lack of options.

Original languageEnglish
Pages (from-to)311-323
Number of pages13
JournalHIV Clinical Trials
Volume4
Issue number5
DOIs
Publication statusPublished - Sep 2003

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Highly Active Antiretroviral Therapy
Protease Inhibitors
Area Under Curve
CD4 Lymphocyte Count
Viral Load
T-Lymphocytes
Reverse Transcriptase Inhibitors
Viremia
Nucleosides
Italy
Linear Models
Therapeutics
Multivariate Analysis
HIV

Keywords

  • HAART response
  • Long-term immunological outcome
  • Predictors

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Predictors of long-term immunological outcome in rebounding patients on protease inhibitor-based HAART after initial successful virologic suppression : Implications for timing to switch. / Tomasoni, Lina Rachele; Patroni, Andrea; Torti, Carlo; Paraninfo, Giuseppe; Gargiulo, Franco; Quiros-Roldan, Eugenia; Uccelli, Maria Cristina; Airò, Paolo; Tinelli, Carmine; Carosi, Giampero; Castelli, Francesco; Casari, S.; Pan, A.; Airoldi, M.; Fausti, C.; El Hamad, I.; Moretti, F.; Pezzoli, C.; Poni Gore, R.; Beltrame, A.; Nasta, P.; Scudeller, L.

In: HIV Clinical Trials, Vol. 4, No. 5, 09.2003, p. 311-323.

Research output: Contribution to journalArticle

Tomasoni, LR, Patroni, A, Torti, C, Paraninfo, G, Gargiulo, F, Quiros-Roldan, E, Uccelli, MC, Airò, P, Tinelli, C, Carosi, G, Castelli, F, Casari, S, Pan, A, Airoldi, M, Fausti, C, El Hamad, I, Moretti, F, Pezzoli, C, Poni Gore, R, Beltrame, A, Nasta, P & Scudeller, L 2003, 'Predictors of long-term immunological outcome in rebounding patients on protease inhibitor-based HAART after initial successful virologic suppression: Implications for timing to switch', HIV Clinical Trials, vol. 4, no. 5, pp. 311-323. https://doi.org/10.1310/FGMF-Y0LY-DMX8-371V
Tomasoni, Lina Rachele ; Patroni, Andrea ; Torti, Carlo ; Paraninfo, Giuseppe ; Gargiulo, Franco ; Quiros-Roldan, Eugenia ; Uccelli, Maria Cristina ; Airò, Paolo ; Tinelli, Carmine ; Carosi, Giampero ; Castelli, Francesco ; Casari, S. ; Pan, A. ; Airoldi, M. ; Fausti, C. ; El Hamad, I. ; Moretti, F. ; Pezzoli, C. ; Poni Gore, R. ; Beltrame, A. ; Nasta, P. ; Scudeller, L. / Predictors of long-term immunological outcome in rebounding patients on protease inhibitor-based HAART after initial successful virologic suppression : Implications for timing to switch. In: HIV Clinical Trials. 2003 ; Vol. 4, No. 5. pp. 311-323.
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abstract = "Objective: To assess predictive factors of long-term immune restoration in patients who started protease inhibitor (PI)-based HAART and experienced virological rebound after initial complete success. Method: A retrospective longitudinal analysis of all HIV-infected patients who started their first PI-based HAART and reached viral load below 500 copies/mL was carried out in a large academic center in Italy. Patients were classified either as complete virologic responder (CR) or rebounders (REB) when confirmed plasma viremia was detected thereafter. Immunological outcome was the area under the curve (AUC) of the absolute CD4+ cell count change since the 8th month after treatment initiation (CD4+ T-cell AUC). Association between baseline characteristics, virological outcome, and CD4+T-cell AUC was assessed by univariate and multivariate analysis. Results: There were 374 patients who were included in the study. Mean follow-up was 30.2 months. There were 226/374 patients (60.4{\%}) who remained CR while 148/374 (39.6{\%}) presented at least one rebound (REB). Among REB patients, complete viral suppression was regained in 15/42 (35.7{\%}) and 50/106 (47.1{\%}) patients who underwent therapy changes or not, respectively. When multiple linear regression was carried out, previous nucleoside reverse transcriptase inhibitor (NRTI) experience and baseline CD4+ cell count below 350 cells/μL did not impair long-term immune restoration. The occurrence of rebound, its duration (>18 months), and its magnitude (peak of viral load > 10,000 copies/mL) were independent negative prognostic factors. Conclusion: The occurrence of viral rebound is independently associated with significantly impaired long-term immunological restoration. The magnitude of viral rebound (<10,000 copies/mL) and its duration (<18 months) may be useful to identify those rebounding patients who may still profit from maintaining the current failing therapy if a more aggressive approach may be expected to be deleterious for tolerability reasons or lack of options.",
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T1 - Predictors of long-term immunological outcome in rebounding patients on protease inhibitor-based HAART after initial successful virologic suppression

T2 - Implications for timing to switch

AU - Tomasoni, Lina Rachele

AU - Patroni, Andrea

AU - Torti, Carlo

AU - Paraninfo, Giuseppe

AU - Gargiulo, Franco

AU - Quiros-Roldan, Eugenia

AU - Uccelli, Maria Cristina

AU - Airò, Paolo

AU - Tinelli, Carmine

AU - Carosi, Giampero

AU - Castelli, Francesco

AU - Casari, S.

AU - Pan, A.

AU - Airoldi, M.

AU - Fausti, C.

AU - El Hamad, I.

AU - Moretti, F.

AU - Pezzoli, C.

AU - Poni Gore, R.

AU - Beltrame, A.

AU - Nasta, P.

AU - Scudeller, L.

PY - 2003/9

Y1 - 2003/9

N2 - Objective: To assess predictive factors of long-term immune restoration in patients who started protease inhibitor (PI)-based HAART and experienced virological rebound after initial complete success. Method: A retrospective longitudinal analysis of all HIV-infected patients who started their first PI-based HAART and reached viral load below 500 copies/mL was carried out in a large academic center in Italy. Patients were classified either as complete virologic responder (CR) or rebounders (REB) when confirmed plasma viremia was detected thereafter. Immunological outcome was the area under the curve (AUC) of the absolute CD4+ cell count change since the 8th month after treatment initiation (CD4+ T-cell AUC). Association between baseline characteristics, virological outcome, and CD4+T-cell AUC was assessed by univariate and multivariate analysis. Results: There were 374 patients who were included in the study. Mean follow-up was 30.2 months. There were 226/374 patients (60.4%) who remained CR while 148/374 (39.6%) presented at least one rebound (REB). Among REB patients, complete viral suppression was regained in 15/42 (35.7%) and 50/106 (47.1%) patients who underwent therapy changes or not, respectively. When multiple linear regression was carried out, previous nucleoside reverse transcriptase inhibitor (NRTI) experience and baseline CD4+ cell count below 350 cells/μL did not impair long-term immune restoration. The occurrence of rebound, its duration (>18 months), and its magnitude (peak of viral load > 10,000 copies/mL) were independent negative prognostic factors. Conclusion: The occurrence of viral rebound is independently associated with significantly impaired long-term immunological restoration. The magnitude of viral rebound (<10,000 copies/mL) and its duration (<18 months) may be useful to identify those rebounding patients who may still profit from maintaining the current failing therapy if a more aggressive approach may be expected to be deleterious for tolerability reasons or lack of options.

AB - Objective: To assess predictive factors of long-term immune restoration in patients who started protease inhibitor (PI)-based HAART and experienced virological rebound after initial complete success. Method: A retrospective longitudinal analysis of all HIV-infected patients who started their first PI-based HAART and reached viral load below 500 copies/mL was carried out in a large academic center in Italy. Patients were classified either as complete virologic responder (CR) or rebounders (REB) when confirmed plasma viremia was detected thereafter. Immunological outcome was the area under the curve (AUC) of the absolute CD4+ cell count change since the 8th month after treatment initiation (CD4+ T-cell AUC). Association between baseline characteristics, virological outcome, and CD4+T-cell AUC was assessed by univariate and multivariate analysis. Results: There were 374 patients who were included in the study. Mean follow-up was 30.2 months. There were 226/374 patients (60.4%) who remained CR while 148/374 (39.6%) presented at least one rebound (REB). Among REB patients, complete viral suppression was regained in 15/42 (35.7%) and 50/106 (47.1%) patients who underwent therapy changes or not, respectively. When multiple linear regression was carried out, previous nucleoside reverse transcriptase inhibitor (NRTI) experience and baseline CD4+ cell count below 350 cells/μL did not impair long-term immune restoration. The occurrence of rebound, its duration (>18 months), and its magnitude (peak of viral load > 10,000 copies/mL) were independent negative prognostic factors. Conclusion: The occurrence of viral rebound is independently associated with significantly impaired long-term immunological restoration. The magnitude of viral rebound (<10,000 copies/mL) and its duration (<18 months) may be useful to identify those rebounding patients who may still profit from maintaining the current failing therapy if a more aggressive approach may be expected to be deleterious for tolerability reasons or lack of options.

KW - HAART response

KW - Long-term immunological outcome

KW - Predictors

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