Human Immunodeficiency Virus Type 1 Persistence Following Systemic Chemotherapy for Malignancy

Background. Systemic chemotherapies for various malignancies have been shown to significantly, yet transiently, decrease numbers of CD4(+) T lymphocytes, a major reservoir for human immunodeficiency virus type 1 (HIV-1) infection. However, little is known about the impact of cytoreductive chemotherapy on HIV-1 reservoir dynamics, persistence, and immune responses. Methods. We investigated the changes in peripheral CD4(+) T-cell-associated HIV-1 DNA and RNA levels, lymphocyte activation, viral population structure, and virus-specific immune responses in a longitudinal cohort of 15 HIV-1-infected individuals receiving systemic chemotherapy or subsequent autologous stem cell transplantation for treatment of hematological malignancies and solid tumors. Results. Despite a transient reduction in CD4(+) T cells capable of harboring HIV-1, a 1.7-and 3.3-fold increase in mean CD4(+) T-cell-associated HIV-1 RNA and DNA, respectively, were observed months following completion of chemotherapy in individuals on antiretroviral therapy. We also observed changes in CD4(+) T-cell population diversity and clonal viral sequence expansion during CD4(+) T-cell reconstitution following chemotherapy cessation. Finally, HIV-1 DNA was preferentially, and in some cases exclusively, detected in cytomegalovirus (CMV)-and Epstein-Barr virus (EBV)-responsive CD4(+) T cells following chemotherapy. Conclusions. Expansion of HIV-infected CMV/EBV-specific CD4(+) T cells may contribute to maintenance of the HIV DNA reservoir following chemotherapy.