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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Reconstitution of HIV-1 reservoir following high-dose chemotherapy/autologous stem cell transplantation for lymphoma
AIDS, Volume 33, No. 2, Year 2019
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Description
Autologous stem cell transplantation following high-dose chemotherapy (HDC/ASCT) is the prime model to study the impact of HDC in HIV-1-infected participants. We analyzed the impact of HDC/ASCT on the resurgent reservoir composition and origin.Design:We included retrospectively a homogenous group of HIV-1-infected patients treated for high-risk lymphoma in a reference center with similar chemotherapy regimens.Methods:Thirteen participants treated with HDC/ASCT from 2012 to 2015 were included. A median seven longitudinal blood samples per participant were available. Total HIV-1 DNA levels in peripheral blood mononuclear cells (PBMCs) were quantified by quantitative PCR. In six participants with sustained viral suppression, the highly variable C2V3 viral region was subjected to next-generation sequencing. Maximum-likelihood phylogeny trees were generated from the reconstructed viral haplotypes. Lymphocyte subsets were studied by flow cytometry.Results:PBMC-associated HIV-1 DNA levels were stable over time. Viral diversity decreased along lymphoma treatment, but increased promptly back to prechemotherapy numbers after HDC/ASCT. Blood viral populations from all time-points were intermingled in phylogeny trees: the resurgent reservoir was similar to pre-HDC circulating proviruses. Memory subsets were the main contributor to the early restoration of the CD4 T-cell pool, with a delayed increase in naïve cell counts.Conclusions:The characterization of HIV-1 reservoir in blood revealed a fast and consistent replenishment from memory CD4 T cells after HDC/ASCT. As HDC/ASCT is increasingly involved in HIV cure trials with gene-modified hematopoietic stem cells, the management of infected T cells in HIV-positive autologous transplants will be critical. © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Authors & Co-Authors
Delagrèverie, Héloïse M.
France, Paris
Université Paris Cité
Gérard, Laurence
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Chaillon, Antoine
United States, La Jolla
University of California, San Diego
Roelens, Marie
France, Paris
Inserm
France, Paris
Université Paris Cité
Djerroudi, Lounes
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Salmona, Maud
France, Paris
Université Paris Cité
Larghéro, Jérôme
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Galicier, Lionel
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Simon, Franćois
France, Paris
Université Paris Cité
Oksenhendler, Éric
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Delaugerre, Constance
France, Paris
Université Paris Cité
Statistics
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1097/QAD.0000000000002051
ISSN:
02699370
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative