Perinatally acquired HIV infection is associated with abnormal blood mitochondrial function during childhood/adolescence

Jennifer Jao; Denise L. Jacobson; Jonathan S. Russell; Jiajia Wang; Wendy Yu; Greg S. Gojanovich; Sue Siminski; Laurie Hyzy; Mitchell E. Geffner; Mariana Gerschenson

doi:10.1097/QAD.0000000000002884

Perinatally acquired HIV infection is associated with abnormal blood mitochondrial function during childhood/adolescence

Jennifer Jao^*, Denise L. Jacobson, Jonathan S. Russell, Jiajia Wang, Wendy Yu, Greg S. Gojanovich, Sue Siminski, Laurie Hyzy, Mitchell E. Geffner, Mariana Gerschenson

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Objective:We assessed differences in mitochondrial function between youth living with perinatal HIV (YPHIV) and youth perinatally HIV-exposed but uninfected (YPHEU).Design:Cross-sectional analysis.Methods:We measured lactate and pyruvate values, as well as mitochondrial Complex I and Complex IV activity in peripheral blood mononuclear cells. Logistic or linear regression models were fit, as appropriate, to assess the association between PHIV status and each mitochondrial parameter, adjusted for confounders. We introduced interaction terms to assess effect modification of PHIV status on the relationship between anthropometric factors and each mitochondrial parameter. Among YPHIV, similar regression models were fit to assess the relationship between HIV-associated factors and each mitochondrial outcome.Results:A total of 243 YPHIV and 118 YPHEU were compared. On average, YPHIV had higher lactate/pyruvate ratio (β: 7.511, 95% confidence interval [95% CI]: 0.402, 14.620) and Complex IV activity (β: 0.037, 95% CI: 0.002, 0.072) compared to YPHEU, adjusted for confounders. Among YPHIV, body mass index Z score (BMIZ) and Complex I activity were inversely associated, whereas, among YPHEU, there was a positive association (β for interaction: -0.048, P = 0.003). Among YPHIV, current (β: -0.789, 95% CI: -1.174, -0.404) and nadir CD4⁺% (β: -0.605, 95% CI: -1.086, -0.125) were inversely associated with lactate/pyruvate ratio; higher current (4.491, 95% CI: 0.754, 8.229) and peak (7.978, 95% CI: 1.499, 14.457) HIV RNA levels were positively associated with lactate/pyruvate ratio in adjusted models.Conclusions:Mitochondrial function and substrate utilization appear perturbed in YPHIV compared to YPHEU. Increasing immunosuppression and viremia are associated with mitochondrial dysfunction among YPHIV.

Original language	English (US)
Pages (from-to)	1385-1394
Number of pages	10
Journal	AIDS
Volume	35
Issue number	9
DOIs	https://doi.org/10.1097/QAD.0000000000002884
State	Published - Jul 15 2021

Funding

We thank the participants and families for their participation in PHACS, and the individuals and institutions involved in the conduct of PHACS. The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute on Alcohol Abuse and Alcoholism, the Office of AIDS Research, and the National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) (Principal Investigator: George R Seage III; Program Director: Liz Salomon) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson). Funding sources: This project was supported in part by R01NR012885 (Gerschenson), P30GM103341 (Gerschenson), and P20GM113134 (Gerschenson). The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) with co-funding from the National Institute of Dental & Craniofacial Research (NIDCR), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), Office of AIDS Research (OAR), the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) and the Tulane University School of Medicine (HD052104).

Keywords

children with HIV
metabolic
mitochondria
mitochondrial function
perinatal HIV

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/QAD.0000000000002884

Cite this

@article{5b20c53a833a45e9b27695965b0bcf9a,

title = "Perinatally acquired HIV infection is associated with abnormal blood mitochondrial function during childhood/adolescence",

abstract = "Objective:We assessed differences in mitochondrial function between youth living with perinatal HIV (YPHIV) and youth perinatally HIV-exposed but uninfected (YPHEU).Design:Cross-sectional analysis.Methods:We measured lactate and pyruvate values, as well as mitochondrial Complex I and Complex IV activity in peripheral blood mononuclear cells. Logistic or linear regression models were fit, as appropriate, to assess the association between PHIV status and each mitochondrial parameter, adjusted for confounders. We introduced interaction terms to assess effect modification of PHIV status on the relationship between anthropometric factors and each mitochondrial parameter. Among YPHIV, similar regression models were fit to assess the relationship between HIV-associated factors and each mitochondrial outcome.Results:A total of 243 YPHIV and 118 YPHEU were compared. On average, YPHIV had higher lactate/pyruvate ratio (β: 7.511, 95% confidence interval [95% CI]: 0.402, 14.620) and Complex IV activity (β: 0.037, 95% CI: 0.002, 0.072) compared to YPHEU, adjusted for confounders. Among YPHIV, body mass index Z score (BMIZ) and Complex I activity were inversely associated, whereas, among YPHEU, there was a positive association (β for interaction: -0.048, P = 0.003). Among YPHIV, current (β: -0.789, 95% CI: -1.174, -0.404) and nadir CD4+% (β: -0.605, 95% CI: -1.086, -0.125) were inversely associated with lactate/pyruvate ratio; higher current (4.491, 95% CI: 0.754, 8.229) and peak (7.978, 95% CI: 1.499, 14.457) HIV RNA levels were positively associated with lactate/pyruvate ratio in adjusted models.Conclusions:Mitochondrial function and substrate utilization appear perturbed in YPHIV compared to YPHEU. Increasing immunosuppression and viremia are associated with mitochondrial dysfunction among YPHIV.",

keywords = "children with HIV, metabolic, mitochondria, mitochondrial function, perinatal HIV",

author = "Jennifer Jao and Jacobson, {Denise L.} and Russell, {Jonathan S.} and Jiajia Wang and Wendy Yu and Gojanovich, {Greg S.} and Sue Siminski and Laurie Hyzy and Geffner, {Mitchell E.} and Mariana Gerschenson",

note = "Funding Information: We thank the participants and families for their participation in PHACS, and the individuals and institutions involved in the conduct of PHACS. The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute on Alcohol Abuse and Alcoholism, the Office of AIDS Research, and the National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) (Principal Investigator: George R Seage III; Program Director: Liz Salomon) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson). Funding Information: Funding sources: This project was supported in part by R01NR012885 (Gerschenson), P30GM103341 (Gerschenson), and P20GM113134 (Gerschenson). The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) with co-funding from the National Institute of Dental & Craniofacial Research (NIDCR), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), Office of AIDS Research (OAR), the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) and the Tulane University School of Medicine (HD052104). Publisher Copyright: {\textcopyright} 2021 Lippincott Williams and Wilkins. All rights reserved.",

year = "2021",

month = jul,

day = "15",

doi = "10.1097/QAD.0000000000002884",

language = "English (US)",

volume = "35",

pages = "1385--1394",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "9",

}

TY - JOUR

T1 - Perinatally acquired HIV infection is associated with abnormal blood mitochondrial function during childhood/adolescence

AU - Jao, Jennifer

AU - Jacobson, Denise L.

AU - Russell, Jonathan S.

AU - Wang, Jiajia

AU - Yu, Wendy

AU - Gojanovich, Greg S.

AU - Siminski, Sue

AU - Hyzy, Laurie

AU - Geffner, Mitchell E.

AU - Gerschenson, Mariana

N1 - Funding Information: We thank the participants and families for their participation in PHACS, and the individuals and institutions involved in the conduct of PHACS. The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute on Alcohol Abuse and Alcoholism, the Office of AIDS Research, and the National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) (Principal Investigator: George R Seage III; Program Director: Liz Salomon) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson). Funding Information: Funding sources: This project was supported in part by R01NR012885 (Gerschenson), P30GM103341 (Gerschenson), and P20GM113134 (Gerschenson). The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) with co-funding from the National Institute of Dental & Craniofacial Research (NIDCR), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), Office of AIDS Research (OAR), the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) and the Tulane University School of Medicine (HD052104). Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved.

PY - 2021/7/15

Y1 - 2021/7/15

N2 - Objective:We assessed differences in mitochondrial function between youth living with perinatal HIV (YPHIV) and youth perinatally HIV-exposed but uninfected (YPHEU).Design:Cross-sectional analysis.Methods:We measured lactate and pyruvate values, as well as mitochondrial Complex I and Complex IV activity in peripheral blood mononuclear cells. Logistic or linear regression models were fit, as appropriate, to assess the association between PHIV status and each mitochondrial parameter, adjusted for confounders. We introduced interaction terms to assess effect modification of PHIV status on the relationship between anthropometric factors and each mitochondrial parameter. Among YPHIV, similar regression models were fit to assess the relationship between HIV-associated factors and each mitochondrial outcome.Results:A total of 243 YPHIV and 118 YPHEU were compared. On average, YPHIV had higher lactate/pyruvate ratio (β: 7.511, 95% confidence interval [95% CI]: 0.402, 14.620) and Complex IV activity (β: 0.037, 95% CI: 0.002, 0.072) compared to YPHEU, adjusted for confounders. Among YPHIV, body mass index Z score (BMIZ) and Complex I activity were inversely associated, whereas, among YPHEU, there was a positive association (β for interaction: -0.048, P = 0.003). Among YPHIV, current (β: -0.789, 95% CI: -1.174, -0.404) and nadir CD4+% (β: -0.605, 95% CI: -1.086, -0.125) were inversely associated with lactate/pyruvate ratio; higher current (4.491, 95% CI: 0.754, 8.229) and peak (7.978, 95% CI: 1.499, 14.457) HIV RNA levels were positively associated with lactate/pyruvate ratio in adjusted models.Conclusions:Mitochondrial function and substrate utilization appear perturbed in YPHIV compared to YPHEU. Increasing immunosuppression and viremia are associated with mitochondrial dysfunction among YPHIV.

AB - Objective:We assessed differences in mitochondrial function between youth living with perinatal HIV (YPHIV) and youth perinatally HIV-exposed but uninfected (YPHEU).Design:Cross-sectional analysis.Methods:We measured lactate and pyruvate values, as well as mitochondrial Complex I and Complex IV activity in peripheral blood mononuclear cells. Logistic or linear regression models were fit, as appropriate, to assess the association between PHIV status and each mitochondrial parameter, adjusted for confounders. We introduced interaction terms to assess effect modification of PHIV status on the relationship between anthropometric factors and each mitochondrial parameter. Among YPHIV, similar regression models were fit to assess the relationship between HIV-associated factors and each mitochondrial outcome.Results:A total of 243 YPHIV and 118 YPHEU were compared. On average, YPHIV had higher lactate/pyruvate ratio (β: 7.511, 95% confidence interval [95% CI]: 0.402, 14.620) and Complex IV activity (β: 0.037, 95% CI: 0.002, 0.072) compared to YPHEU, adjusted for confounders. Among YPHIV, body mass index Z score (BMIZ) and Complex I activity were inversely associated, whereas, among YPHEU, there was a positive association (β for interaction: -0.048, P = 0.003). Among YPHIV, current (β: -0.789, 95% CI: -1.174, -0.404) and nadir CD4+% (β: -0.605, 95% CI: -1.086, -0.125) were inversely associated with lactate/pyruvate ratio; higher current (4.491, 95% CI: 0.754, 8.229) and peak (7.978, 95% CI: 1.499, 14.457) HIV RNA levels were positively associated with lactate/pyruvate ratio in adjusted models.Conclusions:Mitochondrial function and substrate utilization appear perturbed in YPHIV compared to YPHEU. Increasing immunosuppression and viremia are associated with mitochondrial dysfunction among YPHIV.

KW - children with HIV

KW - metabolic

KW - mitochondria

KW - mitochondrial function

KW - perinatal HIV

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U2 - 10.1097/QAD.0000000000002884

DO - 10.1097/QAD.0000000000002884

M3 - Article

C2 - 33730749

AN - SCOPUS:85111787986

SN - 0269-9370

VL - 35

SP - 1385

EP - 1394

JO - AIDS

JF - AIDS

IS - 9

ER -

Perinatally acquired HIV infection is associated with abnormal blood mitochondrial function during childhood/adolescence

Abstract

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Keywords

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UN SDGs

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