title: Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell transplantation for AIDS-related lymphoma patients.
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/10(6) autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA copies/10(6) 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 (R(2) = 0.84, p = 0.01) to month 12 follow-up (R(2) = 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.
authors.affiliation: 1 Microbiology, Immunology, and Virology Unit, CRO National Cancer Institute , Aviano, Italy .
authors.forename: Stefania
authors.initials: S
authors.lastname: Zanussi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bortolin
authors.forename: Chiara
authors.initials: C
authors.lastname: Pratesi
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Tedeschi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Basaglia
authors.forename: Luciano
authors.initials: L
authors.lastname: Abbruzzese
authors.forename: Mario
authors.initials: M
authors.lastname: Mazzucato
authors.forename: Michele
authors.initials: M
authors.lastname: Spina
authors.forename: Emanuela
authors.initials: E
authors.lastname: Vaccher
authors.forename: Umberto
authors.initials: U
authors.lastname: Tirelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Rupolo
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Michieli
authors.forename: Michele
authors.initials: M
authors.lastname: Di Mascio
authors.forename: Paolo
authors.initials: P
authors.lastname: De Paoli
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015497:HIV-1 / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014182:Transplantation, Autologous; D019562:Viral Load / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors