title: Impact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy.
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.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Cillo
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Supriya
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: McMahon
authors.affiliation: Department of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Mitsuyasu
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Para
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000821:virology; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D014766:Viremia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D004279:DNA, Viral