Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/61088
Type
ArticleCopyright
Restricted access
Embargo date
2030-12-31
Collections
- INI - Artigos de Periódicos [3645]
Metadata
Show full item record
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
Author
Epeldegui, Marta
Di, Chang
Lee, Jeannette
Magpantay, Larry I.
Borok, Margaret
Bukuru, Aggrey
Busakhala, Naftali
Godfrey, Catherine
Hosseinipour, Mina C.
Kang, Minhee
Kanyama, Cecilia
Langat, Deborah
Mngqibisa, Rosie
Mwelase, Noluthando
Nyirenda, Mulinda
Samaneka, Wadzanai
Hoagland, Brenda
Campbell, Thomas B.
Martínez-Maza, Otoniel
Krown, Susan E.
Di, Chang
Lee, Jeannette
Magpantay, Larry I.
Borok, Margaret
Bukuru, Aggrey
Busakhala, Naftali
Godfrey, Catherine
Hosseinipour, Mina C.
Kang, Minhee
Kanyama, Cecilia
Langat, Deborah
Mngqibisa, Rosie
Mwelase, Noluthando
Nyirenda, Mulinda
Samaneka, Wadzanai
Hoagland, Brenda
Campbell, Thomas B.
Martínez-Maza, Otoniel
Krown, Susan E.
Affilliation
Department of Obstetrics and Gynecology. University of California. Los Angeles, CA, USA.
Department of Biostatistics. University of Arkansas for Medical Sciences. Little Rock, AR.
Department of Biostatistics. University of Arkansas for Medical Sciences. Little Rock, AR.
Department of Obstetrics and Gynecology. University of California. Los Angeles, CA, USA.
Unit of Internal Medicine. Faculty of Medicine and Health Sciences. University of Zimbabwe. Harare, Zimbabwe.
Joint Clinical Research Center. Kampala, Uganda.
Department of Pharmacology. Moi University School of Medicine. Eldoret, Kenya.
Office of the Global AIDS Coordinator. Department of State. Washington, DC, USA.
Department of Medicine. Division of Infectious Diseases. University of North Carolina Project. Lilongwe, Malawi.
Center for Biostatistics in AIDS Research in the Department of Biostatistics. Harvard School of Public Health. Boston, MA, USA.
Department of Medicine. Division of Infectious Diseases. University of North Carolina Project. Lilongwe, Malawi.
Department of Research. KEMRI Walter Reed Project. Kericho, Kenya.
Research Unit. Enhancing Care Foundation. Durban International Clinical Research Site. King Edward Hospital. Enhancing Care Foundation. Durban, South Africa.
Department of Internal Medicine. University of Witwatersrand. Johannesburg, South Africa.
College of Medicine-Johns Hopkins Research Project. Blantyre, Malawi.
Unit of Internal Medicine. Faculty of Medicine and Health Sciences. University of Zimbabwe. Harare, Zimbabwe.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Department of Infectious Diseases. Rio de Janeiro, RJ, Brazil.
Department of Medicine. University of Colorado School of Medicine Aurora. Colorado, CO, USA.
Department of Obstetrics and Gynecology. University of California. Los Angeles, CA, USA.
Department of Medicine. Memorial Sloan-Kettering Cancer Center (Emerita). New York, NY, USA.
Department of Biostatistics. University of Arkansas for Medical Sciences. Little Rock, AR.
Department of Biostatistics. University of Arkansas for Medical Sciences. Little Rock, AR.
Department of Obstetrics and Gynecology. University of California. Los Angeles, CA, USA.
Unit of Internal Medicine. Faculty of Medicine and Health Sciences. University of Zimbabwe. Harare, Zimbabwe.
Joint Clinical Research Center. Kampala, Uganda.
Department of Pharmacology. Moi University School of Medicine. Eldoret, Kenya.
Office of the Global AIDS Coordinator. Department of State. Washington, DC, USA.
Department of Medicine. Division of Infectious Diseases. University of North Carolina Project. Lilongwe, Malawi.
Center for Biostatistics in AIDS Research in the Department of Biostatistics. Harvard School of Public Health. Boston, MA, USA.
Department of Medicine. Division of Infectious Diseases. University of North Carolina Project. Lilongwe, Malawi.
Department of Research. KEMRI Walter Reed Project. Kericho, Kenya.
Research Unit. Enhancing Care Foundation. Durban International Clinical Research Site. King Edward Hospital. Enhancing Care Foundation. Durban, South Africa.
Department of Internal Medicine. University of Witwatersrand. Johannesburg, South Africa.
College of Medicine-Johns Hopkins Research Project. Blantyre, Malawi.
Unit of Internal Medicine. Faculty of Medicine and Health Sciences. University of Zimbabwe. Harare, Zimbabwe.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Department of Infectious Diseases. Rio de Janeiro, RJ, Brazil.
Department of Medicine. University of Colorado School of Medicine Aurora. Colorado, CO, USA.
Department of Obstetrics and Gynecology. University of California. Los Angeles, CA, USA.
Department of Medicine. Memorial Sloan-Kettering Cancer Center (Emerita). New York, NY, USA.
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. Trial registration: ClinicalTrials.gov NCT01352117.
Share