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Predictive Value of Serum Biomarkers for Response of Limited-Stage AIDS-Associated Kaposi Sarcoma to Antiretroviral Therapy With or Without Concomitant Chemotherapy in Resource-Limited Settings.
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- Author(s): Epeldegui, Marta1 ; Di Chang2; Lee, Jeannette2; Magpantay, Larry I.1; Borok, Margaret3; Bukuru, Aggrey4; Busakhala, Naftali5; Godfrey, Catherine6; Hosseinipour, Mina C.7; Minhee Kang8; Kanyama, Cecilia7; Langat, Deborah9; Mngqibisa, Rosie10; Mwelase, Noluthando11; Nyirenda, Mulinda12; Samaneka, Wadzanai3; Hoagland, Brenda13; Campbell, Thomas B.14; Martínez-Maza, Otoniel1; Krown, Susan E.15
- Source:
JAIDS: Journal of Acquired Immune Deficiency Syndromes. Oct2023, Vol. 94 Issue 2, p165-173. 9p. - Source:
- Additional Information
- Abstract: Background: Guidelines for limited-stage human immunodefi- ciency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking. Setting: We studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART. Methods: Serum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART. Results: Pretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammationassociated biomarkers and increasing levels post-treatment. Conclusions: Quantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of JAIDS: Journal of Acquired Immune Deficiency Syndromes is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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