CD4+ T cells rebound in HIV patients after chemotherapy

Despite a temporary — and in some cases “profound” — reduction in CD4+ T cells that were capable of harboring HIV, CD4+ T cell-associated viral nucleic acid increased in several patients on ART following chemotherapy for various malignancies, according to researchers.

Despite powerfully effective treatments that suppress HIV to undetectable levels, the viral reservoir persists. Hope for an HIV cure was raised after it was discovered that chemotherapy may eradicate lingering HIV–infected cells, opening up a new research frontier.  

“Systemic cytoreductive chemotherapy used to treat various malignancies has been shown to significantly, yet transiently, decrease circulating and tissue-based CD4+ T lymphocytes and monocyte-derived cells,” Daniel R. Kuritzkes, MD, of the division of infectious diseases at Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote. “However, the effects of systemic cancer chemotherapies, with or without concomitant rituximab, on HIV persistence are poorly understood, and there are few data regarding the effects of chemotherapy on HIV–specific immune responses, immune activation or viral evolution. The reduction in CD4+ T cells in the setting of cytoreductive chemotherapy and subsequent cellular proliferation during post-chemotherapy immune reconstitution offers a window into the mechanisms by which HIV–infected cell pools persist or even expand over time with the potential to provide unique insights into reservoir dynamics.”

The researchers carried out a prospective cohort study of 15 patients with HIV who were undergoing chemotherapy (n = 13) or autologous stem cell transplantation (n = 2) for either solid tumors or hematological malignancies. Kuritzkes and colleagues evaluated changes in lymphocyte activation, virus-specific immune responses, viral population structure and changes in peripheral CD4+ T cell-associated HIV DNA and RNA. Most patients had diffuse large B cell lymphoma, and received CHOP or EPOCH and concomitant rituximab for at least five cycles.

Although CD4+ T cell counts declined during chemotherapy, the researchers reported, mean CD4+ T cell-associated HIV RNA rose 1.7-fold after chemotherapy, whereas CD4+ T cell-associated DNA saw a 3.3-fold increase. Kuritzkes and colleagues wrote that after the cessation of chemotherapy, they detected HIV most prominently, “and in some cases exclusively,” in cells that were responsive to cytomegalovirus and Epstein-Barr virus.

The researchers acknowledged that the study was limited by its small sample size and by the fact that many patients were either not receiving ART during cancer treatment or were newly diagnosed with HIV at the same time as the presentation of their cancers.

“Nonetheless, we identified several important findings relevant to the understanding of HIV persistence … and critical insights regarding antigen specificity of the reservoir may be further investigated in more diverse cohorts,” the researchers wrote. – by Andy Polhamus

 

Disclosure: The researchers report no relevant financial disclosures.