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Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy
by
Rubin, Leah H.
, Kisakye, Alice
, Deme, Pragney
, Batte, James
, Mayanja, Richard
, Saylor, Deanna
, Yu, Danyang
, Wawer, Maria J.
, Sacktor, Ned C.
, Reynolds, Steven J.
, Nakasujja, Noeline
, Haughey, Norman J.
, Xu, Yanxun
, Anok, Aggrey
, Quinn, Thomas C.
, Nakigozi, Gertrude
in
Adaptation
/ amino acid catabolism
/ amino acid metabolism
/ Amino acids
/ antiretroviral agents
/ Antiretroviral drugs
/ Antiretroviral therapy
/ Art exhibits
/ Bioenergetics
/ blood serum
/ Caffeine
/ Carnitine
/ Chronic illnesses
/ Chronic infection
/ Drug therapy
/ fatty acid oxidation
/ Fatty acids
/ Glucose
/ glucose oxidation
/ Glycolysis
/ HIV
/ HIV infection
/ HIV infections
/ Human immunodeficiency virus
/ Immune response
/ immunometabolism
/ Infections
/ Ketones
/ Lactic acid
/ Lymphocytes
/ Metabolism
/ Metabolites
/ Metabolomics
/ Oxidation
/ pentose phosphate cycle
/ Pentose phosphate pathway
/ people
/ Phosphorylation
/ Serum levels
/ therapeutics
/ Uganda
2022
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Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy
by
Rubin, Leah H.
, Kisakye, Alice
, Deme, Pragney
, Batte, James
, Mayanja, Richard
, Saylor, Deanna
, Yu, Danyang
, Wawer, Maria J.
, Sacktor, Ned C.
, Reynolds, Steven J.
, Nakasujja, Noeline
, Haughey, Norman J.
, Xu, Yanxun
, Anok, Aggrey
, Quinn, Thomas C.
, Nakigozi, Gertrude
in
Adaptation
/ amino acid catabolism
/ amino acid metabolism
/ Amino acids
/ antiretroviral agents
/ Antiretroviral drugs
/ Antiretroviral therapy
/ Art exhibits
/ Bioenergetics
/ blood serum
/ Caffeine
/ Carnitine
/ Chronic illnesses
/ Chronic infection
/ Drug therapy
/ fatty acid oxidation
/ Fatty acids
/ Glucose
/ glucose oxidation
/ Glycolysis
/ HIV
/ HIV infection
/ HIV infections
/ Human immunodeficiency virus
/ Immune response
/ immunometabolism
/ Infections
/ Ketones
/ Lactic acid
/ Lymphocytes
/ Metabolism
/ Metabolites
/ Metabolomics
/ Oxidation
/ pentose phosphate cycle
/ Pentose phosphate pathway
/ people
/ Phosphorylation
/ Serum levels
/ therapeutics
/ Uganda
2022
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Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy
by
Rubin, Leah H.
, Kisakye, Alice
, Deme, Pragney
, Batte, James
, Mayanja, Richard
, Saylor, Deanna
, Yu, Danyang
, Wawer, Maria J.
, Sacktor, Ned C.
, Reynolds, Steven J.
, Nakasujja, Noeline
, Haughey, Norman J.
, Xu, Yanxun
, Anok, Aggrey
, Quinn, Thomas C.
, Nakigozi, Gertrude
in
Adaptation
/ amino acid catabolism
/ amino acid metabolism
/ Amino acids
/ antiretroviral agents
/ Antiretroviral drugs
/ Antiretroviral therapy
/ Art exhibits
/ Bioenergetics
/ blood serum
/ Caffeine
/ Carnitine
/ Chronic illnesses
/ Chronic infection
/ Drug therapy
/ fatty acid oxidation
/ Fatty acids
/ Glucose
/ glucose oxidation
/ Glycolysis
/ HIV
/ HIV infection
/ HIV infections
/ Human immunodeficiency virus
/ Immune response
/ immunometabolism
/ Infections
/ Ketones
/ Lactic acid
/ Lymphocytes
/ Metabolism
/ Metabolites
/ Metabolomics
/ Oxidation
/ pentose phosphate cycle
/ Pentose phosphate pathway
/ people
/ Phosphorylation
/ Serum levels
/ therapeutics
/ Uganda
2022
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Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy
Journal Article
Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy
2022
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Overview
Background: HIV infection results in immunometabolic reprogramming. While we are beginning to understand how this metabolic reprogramming regulates the immune response to HIV infection, we do not currently understand the impact of ART on immunometabolism in people with HIV (PWH). Methods: Serum obtained from HIV-infected (n = 278) and geographically matched HIV seronegative control subjects (n = 300) from Rakai Uganda were used in this study. Serum was obtained before and ~2 years following the initiation of ART from HIV-infected individuals. We conducted metabolomics profiling of the serum and focused our analysis on metabolic substrates and pathways assocaited with immunometabolism. Results: HIV infection was associated with metabolic adaptations that implicated hyperactive glycolysis, enhanced formation of lactate, increased activity of the pentose phosphate pathway (PPP), decreased β-oxidation of long-chain fatty acids, increased utilization of medium-chain fatty acids, and enhanced amino acid catabolism. Following ART, serum levels of ketone bodies, carnitine, and amino acid metabolism were normalized, however glycolysis, PPP, lactate production, and β-oxidation of long-chain fatty acids remained abnormal. Conclusion: Our findings suggest that HIV infection is associated with an increased immunometabolic demand that is satisfied through the utilization of alternative energetic substrates, including fatty acids and amino acids. ART alone was insufficient to completely restore this metabolic reprogramming to HIV infection, suggesting that a sustained impairment of immunometabolism may contribute to chronic immune activation and comorbid conditions in virally suppressed PWH.
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