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

Anthony R Cillo, Supriya Krishnan, Deborah K McMahon, Ronald T Mitsuyasu, Michael F Para, John W Mellors, Anthony R Cillo, Supriya Krishnan, Deborah K McMahon, Ronald T Mitsuyasu, Michael F Para, John W Mellors

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.

Conflict of interest statement

Competing Interests: JWM is a consultant for Gilead Sciences and owns shares of RFS Pharma. These relationships do not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Quantification of HIV-1 from plasma…
Figure 1. Quantification of HIV-1 from plasma and PBMC pre- and post-chemotherapy.
A) Plasma HIV-1 RNA decreased for 5 patients, increased for 3 patients, and was below the limit of detection at both time points for 1 patient. Median viral load pre-chemotherapy was 1 copy/mL versus 4 copies/mL post-chemotherapy. Open symbols indicate undetectable samples. B) Total HIV-1 DNA levels per 106 CD4+ cells decreased in 4 patients and increased in 5 patients. Median HIV-1 DNA levels per 106 CD4+ cells decreased from 355 to 228 copies per 106 CD4+ cells from pre- to post-chemotherapy. C) 2-LTRs were detectable pre-chemotherapy in 2 of 9 patients versus detectable in 3 of 9 post-chemotherapy. Patients with undetectable 2-LTRs at both time points are not shown. Open symbols indicate undetectable samples.

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