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Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use

BACKGROUND: Primary human immunodeficiency virus (HIV) is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to antiretroviral therapy (ART) initiation and substance use impact these immunologic changes. ME...

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Autores principales: Gilada, Trupti, Schnittman, Samuel R, White, Edward, Mercader, Jacqueline, Wang, Yixin, Dasgupta, Sayan, Valdez, Rogelio, Pinto-Santini, Delia, Pasalar, Siavash, Sanchez, Jorge, Gonzales, Pedro, Lama, Javier R, Bender Ignacio, Rachel, Duerr, Ann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124591/
https://www.ncbi.nlm.nih.gov/pubmed/35611350
http://dx.doi.org/10.1093/ofid/ofac155
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author Gilada, Trupti
Schnittman, Samuel R
White, Edward
Mercader, Jacqueline
Wang, Yixin
Dasgupta, Sayan
Valdez, Rogelio
Pinto-Santini, Delia
Pasalar, Siavash
Sanchez, Jorge
Gonzales, Pedro
Lama, Javier R
Bender Ignacio, Rachel
Duerr, Ann
author_facet Gilada, Trupti
Schnittman, Samuel R
White, Edward
Mercader, Jacqueline
Wang, Yixin
Dasgupta, Sayan
Valdez, Rogelio
Pinto-Santini, Delia
Pasalar, Siavash
Sanchez, Jorge
Gonzales, Pedro
Lama, Javier R
Bender Ignacio, Rachel
Duerr, Ann
author_sort Gilada, Trupti
collection PubMed
description BACKGROUND: Primary human immunodeficiency virus (HIV) is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to antiretroviral therapy (ART) initiation and substance use impact these immunologic changes. METHODS: We studied plasma immune activation biomarkers, viral load, and CD4(+) and CD8(+) cell counts in participants from the Sabes primary infection study in Peru, who had been randomized to begin ART immediately after diagnosis vs 24 weeks later. We modeled influence of substance use and duration of HIV infection on biomarkers at baseline and over 24 weeks. RESULTS: Compared to participants enrolled >30 days after HIV acquisition, participants enrolled during acute infection (≤30 days) had higher mean interferon (IFN)–γ and IFN-α2a (1.7-fold and 3.8-fold interquartile range [IQR] higher, respectively). Participants enrolled >30 days after HIV acquisition had higher mean baseline CD8(+) cell count (2.7 times the IQR). Alcohol use (positive phosphatidylethanol level) was associated with elevated IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70), and smoking was associated with higher macrophage inflammatory protein 1α, TNF-α, and IL-12p70. Most biomarkers declined more quickly in participants who initiated ART immediately; however, substance use and duration of HIV infection at enrollment had little influence on rate of decline. CONCLUSIONS: IFN-γ and other biomarkers are elevated during early primary infection, when exposure to HIV antigens is high. Immune activation decreased most quickly in those who started ART during acute/early primary infection. Higher CD8(+) cell counts and a trend toward higher soluble CD163 levels during the 30 days after acquisition suggest the onset of compensatory responses and immune exhaustion.
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spelling pubmed-91245912022-05-23 Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use Gilada, Trupti Schnittman, Samuel R White, Edward Mercader, Jacqueline Wang, Yixin Dasgupta, Sayan Valdez, Rogelio Pinto-Santini, Delia Pasalar, Siavash Sanchez, Jorge Gonzales, Pedro Lama, Javier R Bender Ignacio, Rachel Duerr, Ann Open Forum Infect Dis Major Article BACKGROUND: Primary human immunodeficiency virus (HIV) is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to antiretroviral therapy (ART) initiation and substance use impact these immunologic changes. METHODS: We studied plasma immune activation biomarkers, viral load, and CD4(+) and CD8(+) cell counts in participants from the Sabes primary infection study in Peru, who had been randomized to begin ART immediately after diagnosis vs 24 weeks later. We modeled influence of substance use and duration of HIV infection on biomarkers at baseline and over 24 weeks. RESULTS: Compared to participants enrolled >30 days after HIV acquisition, participants enrolled during acute infection (≤30 days) had higher mean interferon (IFN)–γ and IFN-α2a (1.7-fold and 3.8-fold interquartile range [IQR] higher, respectively). Participants enrolled >30 days after HIV acquisition had higher mean baseline CD8(+) cell count (2.7 times the IQR). Alcohol use (positive phosphatidylethanol level) was associated with elevated IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70), and smoking was associated with higher macrophage inflammatory protein 1α, TNF-α, and IL-12p70. Most biomarkers declined more quickly in participants who initiated ART immediately; however, substance use and duration of HIV infection at enrollment had little influence on rate of decline. CONCLUSIONS: IFN-γ and other biomarkers are elevated during early primary infection, when exposure to HIV antigens is high. Immune activation decreased most quickly in those who started ART during acute/early primary infection. Higher CD8(+) cell counts and a trend toward higher soluble CD163 levels during the 30 days after acquisition suggest the onset of compensatory responses and immune exhaustion. Oxford University Press 2022-03-24 /pmc/articles/PMC9124591/ /pubmed/35611350 http://dx.doi.org/10.1093/ofid/ofac155 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Article
Gilada, Trupti
Schnittman, Samuel R
White, Edward
Mercader, Jacqueline
Wang, Yixin
Dasgupta, Sayan
Valdez, Rogelio
Pinto-Santini, Delia
Pasalar, Siavash
Sanchez, Jorge
Gonzales, Pedro
Lama, Javier R
Bender Ignacio, Rachel
Duerr, Ann
Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use
title Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use
title_full Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use
title_fullStr Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use
title_full_unstemmed Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use
title_short Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use
title_sort immune activation in primary human immunodeficiency virus: influence of duration of infection, treatment, and substance use
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124591/
https://www.ncbi.nlm.nih.gov/pubmed/35611350
http://dx.doi.org/10.1093/ofid/ofac155
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