Impact of Chemotherapy for AIDS-related Lymphoma on Residual Viremia and Cellular HIV-1 DNA in Patients on Suppressive ART
Anthony Cillo*1, S Krishnan2, D McMahon1, R Mitsuyasu3, M Para4, and J Mellors1
1Univ of Pittsburgh, PA, US; 2Harvard Univ, Boston, MA, US; 3Univ of California, Los Angeles, US; and 4Ohio State Univ, Columbus, US
Background: Intensive cytotoxic chemotherapy and allogeneic stem cell transplantation with a CCR5– donor achieved the first cure of HIV-1 infection. It is unclear which components of the patient’s complex therapy eliminated HIV-1 reservoirs. Specifically, the impact of cytotoxic chemotherapy alone is unknown. We therefore investigated the impact of chemotherapy for AIDS lymphoma on HIV-1 reservoirs.
Methods: We studied patients from the ACTG A5001/ALLRT cohort who underwent chemotherapy for AIDS-related lymphoma with uninterrupted ART and suppression of HIV-1 plasma RNA <50 copies/mL throughout treatment. Plasma HIV-1 RNA, total HIV-1 DNA, and 2-LTR circles (2-LTR) in peripheral blood mononuclear cells (PBMC) were measured using qPCR assays with single-copy sensitivity. Pre-ART samples were used to assess the efficiency of PCR amplification. HIV-1– plasma and PBMC controls were run with all samples.
Results: Of the 40 patients in A5001/ALLRT with newly diagnosed AIDS lymphoma,19 had plasma HIV-1 RNA <50 copies/mL on ART before (pre-Cx) and after (post-Cx) chemotherapy, 11 had stored samples at both time points, and 10 had HIV-1 RNA amplified efficiently by qPCR. All patients received moderately intensive chemotherapy for lymphoma (7 Non-Hodgkins; 3 Hodgkins) that achieved durable remission in 9 patients and relapse in 1. Median time from pre-Cx to post-Cx samples was 432 days (range: 90 to 1011). Median CD4+ cell count pre-Cx was 267 cells/µL vs 297 cells/µL post-Cx. Median pre-Cx HIV-1 RNA was 1 copies/mL (range: <0.4 to 67) vs 5 copies/mL (range: <0.5 to 16) post-Cx. Six patients had detectable HIV-1 RNA pre-Cx that showed declines post-Cx (2 becoming undetectable and the others showing 1.5-, 2.0-, 3.0-, and 13-fold decreases). By contrast, 3 of 4 patients with undetectable HIV-1 RNA pre-Cx had detectable HIV-1 RNA post-Cx. Overall, there was no significant difference in the proportion of patients becoming undetectable vs detectable post-Cx (p = 0.6, McNemar’s test). HIV-1 DNA levels also did not change significantly: median pre-Cx HIV-1 DNA was 133 vs 106 copies/106 CD4+ cells post-Cx (median change –18 copies/106 CD4+ cells [p = 0.5]). 2-LTR were detectable pre-Cx in 3 of 10 patients (range: 17 to 200 copies/106 CD4+ cells) and in 4 post-Cx (range: 4 to 78 copies/106 CD4+ cells).
Conclusions: In this preliminary assessment, moderately intensive chemotherapy for AIDS-related lymphoma did not appear to have a significant or sustained impact on persistent HIV-1 reservoirs.