Human Immunodeficiency Virus Type 1 Persistence Following Systemic Chemotherapy for Malignancy

Area of Science:

• Immunology
• Virology
• Oncology

Background:

• Systemic chemotherapy transiently depletes CD4+ T lymphocytes, a key reservoir for human immunodeficiency virus type 1 (HIV-1).
• The impact of cytoreductive chemotherapy on HIV-1 reservoir dynamics, persistence, and immune responses remains poorly understood.

Purpose of the Study:

• To investigate changes in HIV-1 DNA/RNA levels, lymphocyte activation, viral diversity, and immune responses in HIV-1 infected individuals undergoing chemotherapy.
• To elucidate the role of chemotherapy in HIV-1 reservoir dynamics and persistence.

Main Methods:

• Longitudinal cohort study of 15 HIV-1 infected individuals receiving chemotherapy or autologous stem cell transplantation.
• Analysis of peripheral CD4+ T-cell-associated HIV-1 DNA and RNA, lymphocyte activation markers, viral population structure, and virus-specific immune responses.

Main Results:

• A transient reduction in CD4+ T cells was observed, followed by a 1.7-fold increase in HIV-1 RNA and 3.3-fold increase in HIV-1 DNA months post-chemotherapy.
• Changes in CD4+ T-cell diversity and clonal viral expansion occurred during T-cell reconstitution after chemotherapy cessation.
• HIV-1 DNA was preferentially detected in cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-responsive CD4+ T cells.

Conclusions:

• Expansion of HIV-infected CMV/EBV-specific CD4+ T cells may contribute to the persistence of the HIV DNA reservoir after chemotherapy.
• These findings highlight a potential mechanism for HIV reservoir maintenance in patients treated for malignancies.