Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell transplantation for AIDS-related lymphoma patients

Stefania Zanussi, Maria Teresa Bortolin, Chiara Pratesi, Rosamaria Tedeschi, Giancarlo Basaglia, Luciano Abbruzzese, Mario Mazzucato, Michele Spina, Emanuela Vaccher, Umberto Tirelli, Maurizio Rupolo, Mariagrazia Michieli, Michele Di Mascio, Paolo De Paoli

Research output: Contribution to journalArticle

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Abstract

Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients. Among them seven discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive quantitative real-time polymerase chain reaction (PCR). After debulking chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA copies/106 autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA copies/106 peripheral blood mononuclear cells (PBMCs), range 13-479, p=0.03]. After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a plateau between month 6 and 12 of follow-up. No association was found between peripheral HIV-DNA levels at baseline and after infusion in both cART interrupting and not interrupting patients. Only in the last subgroup, a stable significant linear association between autograft and peripheral blood HIV-1 reservoir emerged from month 1 (R2=0.84, p=0.01) to month 12 follow-up (R2=0.99, p=0.0005). In summary, autograft HIV-1 reservoir size could be influenced by the mobilization phase and predicts posttransplant peripheral HIV-1 reservoir size in patients on continuous cART. These findings could promote new research on strategies reducing the HIV-1 reservoir by using the ASCT procedure.

Original languageEnglish
Pages (from-to)150-159
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

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AIDS-Related Lymphoma
Autografts
Stem Cell Transplantation
HIV-1
HIV
DNA
Transplantation
Therapeutics
Drug Therapy
HIV Infections
Real-Time Polymerase Chain Reaction
Lymphoma
Blood Cells

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell transplantation for AIDS-related lymphoma patients. / Zanussi, Stefania; Bortolin, Maria Teresa; Pratesi, Chiara; Tedeschi, Rosamaria; Basaglia, Giancarlo; Abbruzzese, Luciano; Mazzucato, Mario; Spina, Michele; Vaccher, Emanuela; Tirelli, Umberto; Rupolo, Maurizio; Michieli, Mariagrazia; Di Mascio, Michele; De Paoli, Paolo.

In: AIDS Research and Human Retroviruses, Vol. 31, No. 1, 01.01.2015, p. 150-159.

Research output: Contribution to journalArticle

Zanussi, Stefania ; Bortolin, Maria Teresa ; Pratesi, Chiara ; Tedeschi, Rosamaria ; Basaglia, Giancarlo ; Abbruzzese, Luciano ; Mazzucato, Mario ; Spina, Michele ; Vaccher, Emanuela ; Tirelli, Umberto ; Rupolo, Maurizio ; Michieli, Mariagrazia ; Di Mascio, Michele ; De Paoli, Paolo. / Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell transplantation for AIDS-related lymphoma patients. In: AIDS Research and Human Retroviruses. 2015 ; Vol. 31, No. 1. pp. 150-159.
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abstract = "Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients. Among them seven discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive quantitative real-time polymerase chain reaction (PCR). After debulking chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA copies/106 autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA copies/106 peripheral blood mononuclear cells (PBMCs), range 13-479, p=0.03]. After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a plateau between month 6 and 12 of follow-up. No association was found between peripheral HIV-DNA levels at baseline and after infusion in both cART interrupting and not interrupting patients. Only in the last subgroup, a stable significant linear association between autograft and peripheral blood HIV-1 reservoir emerged from month 1 (R2=0.84, p=0.01) to month 12 follow-up (R2=0.99, p=0.0005). In summary, autograft HIV-1 reservoir size could be influenced by the mobilization phase and predicts posttransplant peripheral HIV-1 reservoir size in patients on continuous cART. These findings could promote new research on strategies reducing the HIV-1 reservoir by using the ASCT procedure.",
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