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.

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.