Browsing by Author "Pediatric HIV/AIDS Cohort Study (PHACS)"

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    Changes in insulin sensitivity over time and associated factors in HIV-infected adolescents
    (Lippincott, Williams & Wilkins, 2018-03-13) Geffner, Mitchell E.; Patel, Kunjal; Jacobson, Denise L.; Wu, Julia; Miller, Tracie L.; Hazra, Rohan; Gerschenson, Mariana; Sharma, Tanvi; Silio, Margarita; Jao, Jennifer; Takemoto, Jody K.; Van Dyke, Russell B.; Dimeglio, Linda A.; Pediatric HIV/AIDS Cohort Study (PHACS); Pediatrics, School of Medicine
    OBJECTIVE: To compare prevalence of insulin resistance between perinatally HIV-infected (PHIV+) and perinatally HIV-exposed, but uninfected adolescents (PHEU), determine incidence of and contributory factors to new and resolved cases of insulin resistance in PHIV+, and evaluate glucose metabolism. DESIGN: Cross-sectional design for comparison of prevalence among PHIV+ and PHEU. Longitudinal design for incidence and resolution of insulin resistance among PHIV+ at risk for these outcomes. METHODS: The source population was adolescents from pediatric HIV clinics in the United States and Puerto Rico participating in the Pediatric HIV/AIDS Cohort Study, an ongoing prospective cohort study designed to evaluate impact of HIV infection and its treatment on multiple domains in preadolescents and adolescents. Insulin resistance was assessed by homeostatic model assessment of insulin resistance. Those with incident insulin resistance underwent 2-h oral glucose tolerance test and HbA1c. Baseline demographic, metabolic, and HIV-specific variables were evaluated for association with incident or resolved insulin resistance. RESULTS: Unadjusted prevalence of insulin resistance in PHIV+ was 27.3 versus 34.1% in PHEU. After adjustment for Tanner stage, age, sex, and race/ethnicity, there was no significant difference between groups. Factors positively associated with developing insulin resistance included female sex, higher BMI z score, and higher waist circumference; those associated with resolving insulin resistance included male sex and lower BMI z score. CONCLUSION: Prevalence of insulin resistance in PHIV+ and PHEU was substantially higher than that reported in HIV-uninfected nonoverweight youth, but similar to that in HIV-uninfected obese youth. Factors associated with incident or resolved insulin resistance among PHIV+ were similar to those reported in HIV-negative obese youth. However, a contributory role of HIV infection and/or its treatment to the incident risk of insulin resistance cannot be excluded.
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    Delay in sexual maturation in perinatally HIV-infected youths is mediated by poor growth
    (Lippincott, Williams & Wilkins, 2017-06-01) Bellavia, Andrea; Williams, Paige L.; DiMeglio, Linda A.; Hazra, Rohan; Abzug, Mark J.; Patel, Kunjal; Jacobson, Denise L.; Van Dyke, Russell B.; Geffner, Mitchell E.; International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P219/219C Study; Pediatric HIV/AIDS Cohort Study (PHACS); Pediatrics, School of Medicine
    OBJECTIVE: To evaluate the association between HIV infection and sexual maturation, and mediation of this association by HIV effects on growth. DESIGN: Pooled data were analyzed from two longitudinal cohort studies, the International Maternal Pediatric Adolescent AIDS Clinical Trials P219/219C Study (1993-2007) and the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (2007-2015), including perinatally HIV-infected (PHIV) and HIV-exposed uninfected (PHEU) youths. METHODS: We evaluated age at sexual maturity among 2539 PHIV and PHEU adolescents based on annual physician-assessed pubertal staging measures. Interval-censored regression models were used to evaluate associations of HIV infection with age at maturity. Mediation analyses accounting for height and BMI Z-scores at specific ages were used to estimate direct and indirect effects of HIV infection on age at sexual maturity. RESULTS: Mean ages at sexual maturity for PHIV girls (n = 1032) were 15.5 years for both female breast and pubic hair and 15.9 and 15.8 years for PHIV boys (n = 1054) for genitalia and pubic hair, respectively. PHIV youths matured approximately 6 months later on average than PHEU (n = 221 girls and 232 boys), and this difference persisted after adjustment for race/ethnicity and birth cohort. BMI and height Z-scores mediated the association between HIV infection and later maturation in girls, accounting for up to 74% of the total HIV effect. Only height Z-scores mediated the effect of HIV on male age at maturity, accounting for up to 98% of the HIV effect. CONCLUSION: PHIV youths attain sexual maturity later on average than PHEU youths. Much of this difference may be attributable to deficient growth, suggesting directions for future interventions.
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    Growth Patterns of Uninfected Children Born to Women Living with Perinatally- Versus Non-Perinatally-Acquired HIV
    (Wolters Kluwer, 2022) Yu, Wendy; Jacobson, Denise L.; Williams, Paige L.; Patel, Kunjal; Geffner, Mitchell E.; Van Dyke, Russell B.; Kacanek, Deborah; DiMeglio, Linda A.; Jao, Jennifer; Pediatric HIV/AIDS Cohort Study (PHACS); Pediatrics, School of Medicine
    Objective: The aim of this study was to compare long-term growth between HIV-exposed uninfected children (CHEU) born to women with perinatally acquired HIV (CHEU-PHIV) and CHEU born to women with nonperinatally acquired HIV (CHEU-NPHIV). Design: A longitudinal analysis of anthropometric measurements from a U.S.-based multisite prospective cohort study enrolling CHEU and their mothers since April 2007. Methods: CHEU were evaluated for growth annually from birth through age 5 and again at age 7 years. Z-scores were calculated using U.S. growth references for weight (WTZ), height (HTZ), and weight-for-length or BMI-for-age (WLZ/BMIZ). Mid-upper arm circumference (MUACZ) and triceps skinfold thickness (TSFZ) Z-scores were obtained from ages 1 and 2, respectively, through age 7 years. Piecewise mixed-effects models, overall and stratified by race and sex, were fit to assess differential growth patterns across age by maternal PHIV status. Results: One thousand four hundred fifty-four singleton infants (286 CHEU-PHIV and 1168 CHEU-NPHIV) were included. CHEU-PHIV had slower growth rates than CHEU-NPHIV for WTZ and WLZ/BMIZ at earlier ages and continued to have lower mean WTZ [-0.27, 95% confidence interval (95% CI): -0.50, -0.04] and WLZ/BMIZ (-0.39, 95% CI: -0.67, -0.11) through age 7. Among non-Black boys, CHEU-PHIV had slightly lower WTZ and WLZ/BMIZ at birth than CHEU-NPHIV and these growth deficits persisted through age 7 years. Conclusion: Compared with CHEU-NPHIV, CHEU-PHIV had diminished growth in early childhood with differences most pronounced among non-Black male children. Further longitudinal follow-up of CHEU-PHIV into young adulthood is needed to understand whether these early effects of maternal PHIV status on growth persist and have other health consequences.
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    Phosphaturia in HIV-Exposed Uninfected Neonates Associated with Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy
    (Oxford University Press, 2024) Purswani, Murli U.; Jacobson, Denise L.; DiMeglio, Linda A.; Yao, Tzy-Jyun; Kopp, Jeffrey B.; Van Dyke, Russell B.; Yu, Wendy; Siberry, George K.; Pediatric HIV/AIDS Cohort Study (PHACS); Pediatrics, School of Medicine
    Background: Tenofovir disoproxil fumarate (TDF) is often used in treating pregnant women living with HIV. Third-trimester TDF exposure is associated with a 12% reduction in bone mineral content in HIV-exposed uninfected (HEU) neonates. The potential mechanisms underlying this observation are unknown. Methods: The TDF study enrolled newborns of gestational age ≥36 weeks from the Surveillance Monitoring for Antiretroviral Therapy and Toxicities study based on in utero TDF exposure (TDF use ≥8 weeks in the third trimester vs none). Blood and urine samples were collected cross-sectionally within 30 days of birth to assess renal function (serum creatinine, serum phosphate, eGFR, percent tubular reabsorption of phosphate [PTRP]), and bone turnover (serum parathyroid hormone, 25-OH vitamin D [25(OH)D], and urinary cross-linked N-telopeptide of type 1 collagen). For each biomarker, a LOESS plot was fit using values at age at specimen collection; regression lines over age were fit among samples collected from 4 to 30 days, to compare slopes by TDF exposure. Results: Among 141 neonates, 77 were TDF-exposed and 64 TDF-unexposed. Between age 4 and 30 days, PTRP decreased more rapidly in the TDF-exposed compared to the unexposed group with slopes of -0.58 vs -0.08/day (difference -0.50/day [95% CI -0.88, -0.11]). Slopes for 25(OH)D were similar in both groups, but serum levels were lower in TDF-exposed neonates (median [IQR]: 22 [19, 29] vs 26 [22, 37] ng/mL). No differences were observed for other biomarkers. Conclusions: Third-trimester in utero exposure to TDF is associated with increased urinary loss of phosphate and lower serum concentrations of 25(OH)D in HEU neonates.
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    Safety of Tenofovir Use During Pregnancy: Early Growth Outcomes in HIV-Exposed Uninfected Infants
    (Wolters Kluwer, 2012) Siberry, George K.; Williams, Paige L.; Mendez, Hermann; Seage, George R., III; Jacobson, Denise L.; Hazra, Rohan; Rich, Kenneth C.; Griner, Raymond; Tassiopoulos, Katherine; Kacanek, Deborah; Mofenson, Lynne M.; Miller, Tracie; DiMeglio, Linda A.; Watts, D. Heather; Pediatric HIV/AIDS Cohort Study (PHACS); Pediatrics, School of Medicine
    Objective: To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants. Design: US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure. Methods: We evaluated the association of maternal TDF use during pregnancy with small for gestational age (SGA); low birth weight (LBW, <2.5 kg); weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ), and head circumference-for-age (HCAZ) z-scores at newborn visit; and LAZ, HCAZ, and WAZ at age 1 year. Logistic regression models for LBW and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted linear regression models were used to evaluate LAZ, WAZ, and HCAZ by TDF exposure. Results: Of 2029 enrolled children with maternal antiretroviral information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14% in 2003 to 43% in 2010. There was no difference between those exposed to combination regimens with vs. without TDF for SGA, LBW, and newborn LAZ and HCAZ. However, at age 1 year, infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: -0.17 vs. -0.03, P=0.04; HCAZ: 0.17 vs. 0.42, P=0.02). Conclusion: TDF use during pregnancy was not associated with increased risk for LBW or SGA. The slightly lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy.