Impact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy.

TitleImpact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2014
AuthorsCillo AR, Krishnan S, McMahon DK, Mitsuyasu RT, Para MF, Mellors JW
JournalPLoS One
Volume9
Issue3
Paginatione92118
Date Published2014
ISSN1932-6203
KeywordsAdult, Aged, Antiretroviral Therapy, Highly Active, Cohort Studies, DNA, Viral, HIV Infections, HIV-1, Humans, Leukocytes, Mononuclear, Lymphoma, AIDS-Related, Male, Middle Aged, Viremia
Abstract

The first cure of HIV-1 infection was achieved through complex, multimodal therapy including myeloablative chemotherapy, total body irradiation, anti-thymocyte globulin, and allogeneic stem cell transplantation with a CCR5 delta32 homozygous donor. The contributions of each component of this therapy to HIV-1 eradication are unclear. To assess the impact of cytotoxic chemotherapy alone on HIV-1 persistence, we longitudinally evaluated low-level plasma viremia and HIV-1 DNA in PBMC from patients in the ACTG A5001/ALLRT cohort on suppressive antiretroviral therapy (ART) who underwent chemotherapy for HIV-1 related lymphoma without interrupting ART. Plasma HIV-1 RNA, total HIV-1 DNA and 2-LTR circles (2-LTRs) in PBMC were measured using sensitive qPCR assays. In the 9 patients who received moderately intensive chemotherapy for HIV-1 related lymphoma with uninterrupted ART, low-level plasma HIV-1 RNA did not change significantly with chemotherapy: median HIV-1 RNA was 1 copy/mL (interquartile range: 1.0 to 20) pre-chemotherapy versus 4 copies/mL (interquartile range: 1.0 to 7.0) post-chemotherapy. HIV-1 DNA levels also did not change significantly, with median pre-chemotherapy HIV-1 DNA of 355 copies/106 CD4+ cells versus 228 copies/106 CD4+ cells post-chemotherapy. 2-LTRs were detectable in 2 of 9 patients pre-chemotherapy and in 3 of 9 patients post-chemotherapy. In summary, moderately intensive chemotherapy for HIV-1 related lymphoma in the context of continuous ART did not have a prolonged impact on HIV-1 persistence. Clinical trials registration unique identifier: NCT00001137.

DOI10.1371/journal.pone.0092118
Alternate JournalPLoS ONE
PubMed ID24638072
PubMed Central IDPMC3956871
Grant List5 T32 AI065380-08 / AI / NIAID NIH HHS / United States
AI068636 / AI / NIAID NIH HHS / United States
AI069474 / AI / NIAID NIH HHS / United States
AI069494 / AI / NIAID NIH HHS / United States
AI28697 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States