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 Journal Article


Authors: Epeldegui, M.; Chang, D.; Lee, J.; Magpantay, L. I.; Borok, M.; Bukuru, A.; Busakhala, N.; Godfrey, C.; Hosseinipour, M. C.; Kang, M.; Kanyama, C.; Langat, D.; Mngqibisa, R.; Mwelase, N.; Nyirenda, M.; Samaneka, W.; Hoagland, B.; Campbell, T. B.; Martínez-Maza, O.; Krown, S. E.; for the A5264/AMC-067 team
Article Title: 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
Abstract: BACKGROUND: Guidelines for limited-stage human immunodeficiency 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 inflammation-associated 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. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: vascular endothelial growth factor a; human immunodeficiency virus infection; biomarkers; biological marker; etoposide; interleukin 10; inflammation; vasculotropin a; ligand; ligands; tumor necrosis factor receptor; acquired immune deficiency syndrome; acquired immunodeficiency syndrome; kaposi sarcoma; sarcoma, kaposi; hiv infections; chemoradiotherapy; gelatinase a; interleukin-10; receptors, tumor necrosis factor; complication; matrix metalloproteinase 2; humans; human; resource-limited settings; resource limited setting
Journal Title: JAIDS: Journal of Acquired Immune Deficiency Syndromes
Volume: 94
Issue: 2
ISSN: 1525-4135
Publisher: Lippincott Williams & Wilkins  
Date Published: 2023-10-01
Start Page: 165
End Page: 173
Language: English
DOI: 10.1097/qai.0000000000003236
PUBMED: 37368929
PROVIDER: scopus
PMCID: PMC10527582
DOI/URL:
Notes: Article -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Susan Krown
    156 Krown