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.

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.

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.

Expansion of HIV-infected CMV/EBV-specific CD4 ⁺ T cells may contribute to maintenance of the HIV DNA reservoir following chemotherapy.