Association of In Utero HIV Exposure With Obesity and Reactive Airway Disease in HIV-Negative Adolescents and Young Adults

Fourman, Lindsay T; Pan, Chelsea S; Zheng, Isabel; Gerard, Marisa E; Sheehab, Asia; Lee, Hang; Stanley, Takara L.; Grinspoon, Steven

doi:10.1097/qai.0000000000002235

Cited by 8 publications

(8 citation statements)

References 44 publications

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“…Furthermore, we have found a relationship of lower CD4 + T-cell count during pregnancy with higher HEU BMI z-score during adolescence and young adulthood. 10 By demonstrating a direct link of prenatal CD4 + T-cell count with fetoplacental development, the current study reaffirms the developmental mechanisms of health and disease among HEU individuals that have been suggested by these prior reports. Furthermore, our findings underscore low maternal CD4 + T-cell count as a proxy for a perturbed intrauterine environment in HIV, which may have implications for clinical care.…”

Section: Discussionsupporting

confidence: 86%

“…In this study, we leveraged a longitudinal cohort of HEU adolescents and young adults that we previously developed at a large US academic health center (Partners HealthCare, Boston, MA). 10 Briefly, we searched the Research Patient Data Registry for women who had HIV during pregnancy, labor, or delivery based on the International Classification of Diseases , Ninth Revision coding and also queried the records of their HIV-negative offspring. HEU individuals were required to have been born since 1990 with medical records available beyond 13 years of age.…”

Section: Methodsmentioning

confidence: 99%

“…Data on prenatal, birth, and medical history were obtained from the medical records of HEU adolescents and young adults and their mothers as we have described previously. 10 Sex- and age-adjusted body mass index (BMI) z-score was calculated from the Centers for Disease Control and Prevention growth charts using the most recent weight and height obtained beyond 12 years old. Presence of RAD also was ascertained as defined by a clinical report of “RAD” or “asthma” in the medical record at 12 years or older.…”

Section: Methodsmentioning

confidence: 99%

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Placental Vascular Abnormalities in Association With Prenatal and Long-Term Health Characteristics Among HIV-Exposed Uninfected Adolescents and Young Adults

Fourman

Mueller

Boutin

et al. 2021

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Section: Discussionsupporting

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Placental Vascular Abnormalities in Association With Prenatal and Long-Term Health Characteristics Among HIV-Exposed Uninfected Adolescents and Young Adults

Fourman

Mueller

Boutin

et al. 2021

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Despite the lower weight, HIV exposure has been associated with higher levels of dyslipidemia in children [ 15 , 16 ]. HIV exposure has also been linked to an increased risk of obesity and hypertension in adolescents in the United States [ 17 , 18 ]. The mechanisms by which HIV-exposure influences cardiometabolic health are incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

In-utero HIV exposure and cardiometabolic health among children 5–8 years: findings from a prospective birth cohort in South Africa

Bengtson¹,

Pellowski

McGarvey³

et al. 2022

Aids

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Objective: To evaluate if in-utero HIV exposure is associated with adverse cardiometabolic health outcomes at 5-8 years of age.Design: Prospective cohort study. Methods:We enrolled a random sample of HIV-exposed but uninfected (HEU) and HIV-unexposed children from the Drakenstein Child Health study, a longitudinal birth cohort study in Cape Town, South Africa, in a cardiometabolic health pilot study. Outcomes were assessed by trained study staff and included: anthropometry, body composition and size, blood pressure, fasting plasma glucose, HbA1c, lipids, and insulin resistance using HOMA-IR. We used multivariable linear and log-binomial regression to estimate associations between HIV-exposure and cardiometabolic outcomes, adjusted for child age, sex, height, body size, and maternal factors as appropriate.Results: We included 260 children (HEU n ¼ 100, HIV-unexposed n ¼ 160). HEU children had older mothers (median age 30 vs. 26 years), with minimal differences in gestational age and size at birth by HIV-exposure status. In multivariable analyses, HEU children had lower weight-for-age (mean difference À0.35, 95% confidence interval À0.66, À0.05), and height-for-age (mean difference À0.29, 95% confidence interval À0.56, À0.03; z-scores). There were no differences in adiposity, impaired glucose metabolism, or lipid levels by HIV-exposure status. Overall, 12% of children had blood pressure more than 90th percentile, with no differences by HIV-exposure status.Conclusion: Overall, there were few differences in cardiometabolic outcomes between HEU and HIV-unexposed children in this South African cohort. Although these findings are reassuring, monitoring of cardiometabolic health is important as HEU and HIVunexposed children enter adolescence and cardiometabolic risk trajectories become established.

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“…YPHIV born during the early days of the HIV epidemic who have survived into their youth or young adulthood today are likely to have received lifelong ART, which includes these older NRTIs. Interestingly, in the absence of HIV infection, children exposed to ART perinatally have been found to display higher myocardial and mitochondrial mass which were associated with zidovudine (ZDV) exposure [10]; higher levels of mitochondrial DNA; and a higher prevalence of autism spectrum disorders [11], obesity, and reactive airway disease [12].…”

Section: Introductionmentioning

confidence: 99%

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

Jao

Jacobson

Wang

et al. 2021

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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 (b: 7.511, 95% confidence interval [95% CI]: 0.402, 14.620) and Complex IV activity (b: 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 (b for interaction: À0.048, P ¼ 0.003). Among YPHIV, current (b: À0.789, 95% CI: À1.174, À0.404) and nadir CD4 þ % (b: À0.605, 95% CI: À1.086, À0.125) 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.

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Association of In Utero HIV Exposure With Obesity and Reactive Airway Disease in HIV-Negative Adolescents and Young Adults

Abstract: Bold text denotes statistical significance with P < 0.05. a Median household income was determined based on current adolescent zip code according to U.S. census data. b Maternal BMI was ascertained between 35 and 50 years of age.

Cited by 8 publications

References 44 publications

Placental Vascular Abnormalities in Association With Prenatal and Long-Term Health Characteristics Among HIV-Exposed Uninfected Adolescents and Young Adults

Placental Vascular Abnormalities in Association With Prenatal and Long-Term Health Characteristics Among HIV-Exposed Uninfected Adolescents and Young Adults

In-utero HIV exposure and cardiometabolic health among children 5–8 years: findings from a prospective birth cohort in South Africa

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

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