Lack of Specific Regulatory T Cell Depletion and Cytoreduction Associated with Extensive Toxicity After Administration of Low and High Doses of Cyclophosphamide.
AIDS Res Hum Retroviruses
; 38(1): 45-49, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-33957772
ABSTRACT
Up to 93% of the human immunodeficiency virus (HIV) latent reservoir comprised defective proviruses, suggesting that a functional cure is possible through the elimination of a small population of cells containing intact virus, instead of the entire reservoir. Cyclophosphamide (Cy) is an established chemotherapeutic agent for immune cell cancers. In high doses, Cy is a nonselective cytoreductor, used in allogeneic stem-cell transplantation, while in a low dose, metronomic schedule, Cy selectively depletes regulatory T cells (Tregs). We administered low and high doses to simian immunodeficiency virus (SIV)-infected rhesus macaques (RM) to assess their effects on the SIV reservoirs. As a Treg-depleting agent, Cy unselectively depleted Treg and total lymphocytes, resulting in minimal immune activation and no viral reactivation. As a cytoreductive agent, Cy induced massive viral reactivation in elite controller RMs without ART. However, when administered with antiretroviral therapy (ART), Cy had substantial adverse effects, including mortality. Our study thus dissuades further investigation of Cy as an HIV cure agent.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV Infections
/
Simian Acquired Immunodeficiency Syndrome
/
Simian Immunodeficiency Virus
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
AIDS Res Hum Retroviruses
Journal subject:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Year:
2022
Document type:
Article
Affiliation country:
United States