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8. Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1

Author

Rawat, Pratima, Brummel, Sean S, Singh, Kumud K, Kim, Jihoon, Frazer, Kelly A, Nichols, Sharon, Seage, George R, Williams, Paige L, Van Dyke, Russell B, Harismendy, Olivier, Trout, Rodney N, and Spector, Stephen A

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Infectious Diseases, Clinical Research, HIV/AIDS, Pediatric, Genetics, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, 14-3-3 Proteins, Child, Child, Preschool, Female, Genome-Wide Association Study, Genomics, HIV Infections, HIV-1, Humans, Infant, Infectious Disease Transmission, Vertical, Inflammasomes, Inflammation, Intracellular Signaling Peptides and Proteins, Male, Membrane Proteins, Microglia, Neurocognitive Disorders, Receptors, CCR, IIIV, neurocognitive impairment, IIIV perinatal infection, genome-wide exome sequencing, CCRL2, RETREG1, YWHAH, 14-3-3 eta protein, 14-3-3η protein, HIV, HIV perinatal infection, Biological Sciences, Medical and Health Sciences, Microbiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundWe identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children.MethodsWhole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA)

Published
2021

13. Per‐ and Polyfluoroalkyl Substance Exposure, Gestational Weight Gain, and Postpartum Weight Changes in Project Viva

Author

Mitro, Susanna D, Sagiv, Sharon K, Rifas‐Shiman, Sheryl L, Calafat, Antonia M, Fleisch, Abby F, Jaacks, Lindsay M, Williams, Paige L, Oken, Emily, and James‐Todd, Tamarra M

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Clinical Research, Pediatric, Reproductive health and childbirth, Good Health and Well Being, Adult, Caprylates, Cohort Studies, Female, Fluorocarbons, Gestational Weight Gain, Humans, Postpartum Period, Pregnancy, Prospective Studies, Endocrinology & Metabolism
Abstract

ObjectiveThe purpose of this study was to test the extent to which pregnancy per- and polyfluoroalkyl substance (PFAS) concentrations were associated with gestational weight gain and postpartum weight changes.MethodsThis study was composed of 1,614 women recruited between 1999 and 2002 via the Project Viva cohort with pregnancy plasma concentrations of six PFAS, including perfluorooctanesulfonic acid, perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. Gestational weight gain was defined as the difference between last pregnancy weight and prepregnancy weight, 1-year postpartum weight retention as the difference between 1-year postpartum weight and prepregnancy weight, and 3-year postpartum weight change as the difference between 3-year postpartum weight and prepregnancy weight.ResultsDuring pregnancy, women gained 0.37 kg (95% CI: 0.11-0.62) more weight per doubling of 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. At 1 year post partum, women retained 0.55 kg (95% CI: 0.07-1.04) more weight per doubling of PFOA. At 3 years post partum, women gained 0.91 kg (95% CI: 0.25-1.56) more weight per doubling in PFOA. Findings were similar after adjustment for all PFAS. Other PFAS were not associated with weight changes. Postpartum associations were stronger among women with higher prepregnancy BMI. Models were adjusted for demographics.ConclusionsPregnancy PFAS were associated with greater gestational weight gain, weight retention, and weight gain years after pregnancy.

Published
2020

14. Brain morphometric differences in youth with and without perinatally-acquired HIV: A cross-sectional study

Author

Angeles, C Paula Lewis-de los, Williams, Paige L, Jenkins, Lisanne M, Huo, Yanling, Malee, Kathleen, Alpert, Kathryn I, Uban, Kristina A, Herting, Megan M, Csernansky, John G, Nichols, Sharon L, Van Dyke, Russell B, Sowell, Elizabeth R, Wang, Lei, and for the Pediatric HIV/AIDS Cohort Study and the Pediatric Imaging, Neurocognition

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Pediatric AIDS, HIV/AIDS, Pediatric, Neurosciences, Good Health and Well Being, Adolescent, Brain, Child, Cohort Studies, Cross-Sectional Studies, Female, HIV Infections, Humans, Magnetic Resonance Imaging, Male, Young Adult, Perinatally-acquired HIV, Neurodevelopment, Grey matter, Pediatric HIV/AIDS Cohort Study (PHACS) and the Pediatric Imaging, Neurocognition, and Genetics (PING) Study, Biological psychology, Clinical and health psychology
Abstract

Youth with perinatally-acquired HIV (PHIV) experience specific and global cognitive deficits at increased rates compared to typically-developing HIV-uninfected youth. In youth with PHIV, HIV infects the brain early in development. Neuroimaging studies have demonstrated altered grey matter morphometry in youth with PHIV compared to typically-developing youth. This study examined cortical thickness, surface area, and gyrification of grey matter in youth (age 11-20 years old) with PHIV (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) compared to typically-developing presumed HIV uninfected and unexposed youth (n = 80) from the Pediatric Imaging, Neurocognition and Genetics Study (PING) using structural magnetic resonance imaging. This study also examined the relationship between grey matter morphometry and age. Youth with PHIV had reduced cortical thickness, surface area, and gyrification compared to typically-developing youth. In addition, an inverse relationship between age and grey matter volume was found in typically-developing youth, but was not observed in youth with PHIV. Longitudinal studies are necessary to understand the neurodevelopmental trajectory of youth with PHIV.

Published
2020

15. Brain morphometric differences in youth with and without perinatally-acquired HIV: A cross-sectional study.

Author

Lewis-de Los Angeles, C Paula, Williams, Paige L, Jenkins, Lisanne M, Huo, Yanling, Malee, Kathleen, Alpert, Kathryn I, Uban, Kristina A, Herting, Megan M, Csernansky, John G, Nichols, Sharon L, Van Dyke, Russell B, Sowell, Elizabeth R, Wang, Lei, and Pediatric HIV/AIDS Cohort Study (PHACS) and the Pediatric Imaging, Neurocognition, and Genetics (PING) Study

Subjects
Pediatric HIV/AIDS Cohort Study (PHACS) and the Pediatric Imaging, Neurocognition, and Genetics (PING) Study, Brain, Grey matter, Neurodevelopment, Perinatally-acquired HIV, Pediatric HIV/AIDS Cohort Study (PHACS) and the Pediatric Imaging, Neurocognition, and Genetics (PING) Study, Neurosciences
Abstract

Youth with perinatally-acquired HIV (PHIV) experience specific and global cognitive deficits at increased rates compared to typically-developing HIV-uninfected youth. In youth with PHIV, HIV infects the brain early in development. Neuroimaging studies have demonstrated altered grey matter morphometry in youth with PHIV compared to typically-developing youth. This study examined cortical thickness, surface area, and gyrification of grey matter in youth (age 11-20 years old) with PHIV (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) compared to typically-developing presumed HIV uninfected and unexposed youth (n = 80) from the Pediatric Imaging, Neurocognition and Genetics Study (PING) using structural magnetic resonance imaging. This study also examined the relationship between grey matter morphometry and age. Youth with PHIV had reduced cortical thickness, surface area, and gyrification compared to typically-developing youth. In addition, an inverse relationship between age and grey matter volume was found in typically-developing youth, but was not observed in youth with PHIV. Longitudinal studies are necessary to understand the neurodevelopmental trajectory of youth with PHIV.

Published
2020

22. Bayesian kernel machine regression-causal mediation analysis

Author

Devick, Katrina L., Bobb, Jennifer F., Mazumdar, Maitreyi, Henn, Birgit Claus, Bellinger, David C., Christiani, David C., Wright, Robert O., Williams, Paige L., Coull, Brent A., and Valeri, Linda

Subjects
Statistics - Methodology
Abstract

Greater understanding of the pathways through which an environmental mixture operates is important to design effective interventions. We present new methodology to estimate natural direct and indirect effects and controlled direct effects of a complex mixture exposure on an outcome through a mediator variable. We implement Bayesian Kernel Machine Regression (BKMR) to allow for all possible interactions and nonlinear effects of (1) the co-exposures on the mediator, (2) the co-exposures and mediator on the outcome, and (3) selected covariates on the mediator and/or outcome. From the posterior predictive distributions of the mediator and outcome, we simulate counterfactuals to obtain posterior samples, estimates, and credible intervals of the mediation effects. Our simulation study demonstrates that when the exposure-mediator and exposure-mediator-outcome relationships are complex, BKMR--Causal Mediation Analysis performs better than current mediation methods. We applied our methodology to quantify the contribution of birth length as a mediator between in utero co-exposure to arsenic, manganese and lead, and children's neurodevelopmental scores, in a prospective birth cohort in Bangladesh. Among younger children, we found a negative (adverse) association between the metal mixture and neurodevelopment. We also found evidence that birth length mediates the effect of exposure to the metal mixture on neurodevelopment for younger children. If birth length were fixed to its $75^{th}$ percentile value, the harmful effect of the metal mixture on neurodevelopment is attenuated, suggesting nutritional interventions to help increase fetal growth, and thus birth length, could potentially block the harmful effect of the metal mixture on neurodevelopment., Comment: 22 pages, 12 figures, and 1 tables

Published
2018

23. Markers of Bone Mineral Metabolism and Cardiac Structure and Function in Perinatally HIV-Infected and HIV-Exposed but Uninfected Children and Adolescents.

Author

Margossian, Renee, Williams, Paige L, Yu, Wendy, Jacobson, Denise L, Geffner, Mitchell E, DiMeglio, Linda A, Van Dyke, Russell B, Spector, Stephen A, Schuster, Gertrud U, Stephensen, Charles B, Miller, Tracie L, and Lipshultz, Steven E

Subjects
Clinical Research, Cardiovascular, Pediatric AIDS, Pediatric, HIV/AIDS, Heart Disease, Prevention, Musculoskeletal, Good Health and Well Being, Adolescent, Biomarkers, Bone Density, Bone and Bones, Calcium, Cardiovascular Abnormalities, Child, Cohort Studies, Echocardiography, Female, Fibroblast Growth Factor-23, Fibroblast Growth Factors, HIV Infections, Humans, Infectious Disease Transmission, Vertical, Male, Minerals, Parathyroid Hormone, Phosphates, United States, Vitamin D, 25-hydroxy-vitamin D, parathyroid hormone, cardiac function, HIV infection, children, Pediatric HIV/AIDS Cohort Study, Clinical Sciences, Public Health and Health Services, Virology
Abstract

BackgroundDisordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth.SettingThe Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites.MethodsAmong perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected (PHEU) youth enrolled in the Adolescent Master Protocol, we evaluated associations of vitamin D [measured as 25-hydroxy-vitamin D (25-OHD)], parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function, and concentrations of NT-proBNP, a biomarker of cardiac damage.ResultsAmong 485 participants (305 PHIV and 180 PHEU) with echocardiograms and bone mineralization measures, low 25-OHD (65 pg/mL) was identified more often among PHIV participants than PHEU participants (9% vs 3%, P = 0.02). After adjusting for HIV status and demographic covariates, both low 25-OHD and elevated PTH were associated with lower mean LV mass z-scores, whereas elevated PTH was associated with higher mean fractional shortening z-scores. Participants with low 25-OHD also had slightly higher mean LV end-systolic wall stress z-scores, but differences were more pronounced in PHEU participants than in PHIV participants. FGF-23 was inversely related to end-diastolic septal thickness, both overall and among PHIV participants.ConclusionsIn this cohort of PHIV and PHEU youth, we observed associations of 25-OHD, PTH, and FGF-23 with both structural and functional cardiac parameters, supporting links between bone mineral metabolism and cardiac status.

Published
2019

30. Polybrominated diphenyl ethers and gestational weight gain: a multi‐center prospective cohort study.

Author

Wang, Zifan, Williams, Paige L., Bellavia, Andrea, Wylie, Blair J., Kannan, Kurunthachalam, Bloom, Michael S., Hunt, Kelly J., Hacker, Michele R., Zhang, Cuilin, and James‐Todd, Tamarra

Subjects
*OBESITY in women, *POLYBROMINATED diphenyl ethers, *WEIGHT gain, *FETAL development, *PREGNANT women
Abstract

Objective: To evaluate the associations of plasma polybrominated diphenyl ether (PBDE) concentrations in early pregnancy with gestational weight gain (GWG). Design: Prospective cohort study. Setting: US‐based, multicentre cohort of pregnant women. Population: We used data from 2052 women without obesity and 397 women with obesity participating in the NICHD Fetal Growth Studies – Singleton Cohort, with first‐trimester plasma PBDE concentrations and weight measurements throughout pregnancy. Methods: We applied generalised linear models and Bayesian kernel machine regression (BKMR) to evaluate both the individual and joint associations of PBDEs with measures of GWG, adjusting for potential confounders. Main outcome measures: Total GWG (kg), total and trimester‐specific GWG velocities (kg/week), and GWG categories and trajectory groups. Results: Mean pre‐pregnancy BMIs were 23.6 and 34.5 kg/m2 for women without and with obesity, respectively. Among women without obesity, there were no associations of PBDEs with any GWG measure. Among women with obesity, one standard deviation increase in log‐transformed PBDE 47 was associated with a 1.87 kg higher total GWG (95% CI 0.39–3.35) and a 0.05 kg/week higher total GWG velocity (95% CI 0.01–0.09). Similar associations were found for PBDE 47 in BKMR among women with obesity, and PBDE 47, 99 and 100 were associated with lower odds of being in the low GWG trajectory group. Conclusions: PBDEs were not associated with GWG among individuals without obesity. Among those with obesity, only PBDE 47 showed consistent positive associations with GWG measures across multiple statistical methods. Further research is needed to validate this association and explore potential mechanisms. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Birth Outcomes for Pregnant Women with HIV Using Tenofovir–Emtricitabine

Author

Rough, Kathryn, Seage, George R, Williams, Paige L, Hernandez-Diaz, Sonia, Huo, Yanling, Chadwick, Ellen G, Currier, Judith S, Hoffman, Risa M, Barr, Emily, Shapiro, David E, and Patel, Kunjal

Subjects
Paediatrics, Reproductive Medicine, Biomedical and Clinical Sciences, HIV/AIDS, Pediatric, Infant Mortality, Infectious Diseases, Perinatal Period - Conditions Originating in Perinatal Period, Clinical Research, Preterm, Low Birth Weight and Health of the Newborn, Prevention, Clinical Trials and Supportive Activities, Reproductive health and childbirth, Infection, Good Health and Well Being, Adult, Anti-HIV Agents, Cohort Studies, Disease Transmission, Infectious, Drug Administration Schedule, Drug Therapy, Combination, Emtricitabine, Female, HIV Infections, Humans, Infant, Low Birth Weight, Infant, Newborn, Lamivudine, Lopinavir, Pregnancy, Pregnancy Complications, Infectious, Pregnancy Outcome, Premature Birth, Risk, Ritonavir, Tenofovir, Zidovudine, PHACS and the IMPAACT P1025 Study Teams, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundIn a previous trial of antiretroviral therapy (ART) involving pregnant women with human immunodeficiency virus (HIV) infection, those randomly assigned to receive tenofovir, emtricitabine, and ritonavir-boosted lopinavir (TDF-FTC-LPV/r) had infants at greater risk for very premature birth and death within 14 days after delivery than those assigned to receive zidovudine, lamivudine, and ritonavir-boosted lopinavir (ZDV-3TC-LPV/r).MethodsUsing data from two U.S.-based cohort studies, we compared the risk of adverse birth outcomes among infants with in utero exposure to ZDV-3TC-LPV/r, TDF-FTC-LPV/r, or TDF-FTC with ritonavir-boosted atazanavir (ATV/r). We evaluated the risk of preterm birth (

Published
2018

38. Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) — a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health

Author

Preston, Emma V, primary, Quinn, Marlee R, additional, Williams, Paige L, additional, McElrath, Thomas F, additional, Cantonwine, David E, additional, Seely, Ellen W, additional, Wylie, Blair J, additional, Hacker, Michele R, additional, O'Brien, Karen, additional, Brown, Florence M, additional, Powe, Camille E, additional, Bellavia, Andrea, additional, Wang, Zifan, additional, Tomsho, Kathryn S, additional, Hauser, Russ, additional, and James-Todd, Tamarra, additional

Published
2024
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43. Mediation Analysis for Censored Survival Data under an Accelerated Failure Time Model

Author

Fulcher, Isabel R., Tchetgen, Eric Tchetgen, and Williams, Paige L.

Subjects
Statistics - Methodology
Abstract

Recent advances in causal mediation analysis have formalized conditions for estimating direct and indirect effects in various contexts. These approaches have been extended to a number of models for survival outcomes including accelerated failure time (AFT) models which are widely used in a broad range of health applications given their intuitive interpretation. In this setting, it has been suggested that under standard assumptions, the "difference" and "product" methods produce equivalent estimates of the indirect effect of exposure on the survival outcome. We formally show that these two methods may produce substantially different estimates in the presence of censoring or truncation, due to a form of model misspecification. Specifically, we establish that while the product method remains valid under standard assumptions in the presence of independent censoring, the difference method can be biased in the presence of such censoring whenever the error distribution of the AFT model fails to be collapsible upon marginalizing over the mediator. This will invariably be the case for most choices of mediator and outcome error distributions. A notable exception arises in case of normal mediator-normal outcome where we show consistency of both difference and product estimators in the presence of independent censoring. These results are confirmed in simulation studies and two data applications.

Published
2016

49. Birth Weight and Preterm Delivery Outcomes of Perinatally vs Nonperinatally Human Immunodeficiency Virus-Infected Pregnant Women in the United States: Results From the PHACS SMARTT Study and IMPAACT P1025 Protocol.

Author

Jao, Jennifer, Kacanek, Deborah, Williams, Paige L, Geffner, Mitchell E, Livingston, Elizabeth G, Sperling, Rhoda S, Patel, Kunjal, Bardeguez, Arlene D, Burchett, Sandra K, Chakhtoura, Nahida, Scott, Gwendolyn B, Van Dyke, Russell B, Abrams, Elaine J, Yogev, Ram, Sanders, Margaret Ann, Malee, Kathleen, Hunter, Scott, Shearer, William, Paul, Mary, Cooper, Norma, Harris, Lynnette, Purswani, Murli, Stuard, Emma, Cintron, Anna, Puga, Ana, Cooley, Dia, Garvie, Patricia A, Blood, James, Borkowsky, William, Deygoo, Sandra, Vasserman, Marsha, Dieudonne, Arry, Bettica, Linda, Knapp, Katherine, Allison, Kim, Wilkins, Megan, Acevedo-Flores, Midnela, Angeli-Nieves, Lourdes, Olivera, Vivian, Kohlhoff, Stephan, Dennie, Ava, Bewley, Susan, Dyke, Russell Van, Craig, Karen, Sirois, Patricia, Crain, Marilyn, Hickman, Paige, Marullo, Dan, Spector, Stephen A, Norris, Kim, Nichols, Sharon, McFarland, Elizabeth, Chambers, Carrie, Wallace, Jenna, Barr, Emily, Rathore, Mobeen, Stowers, Kristi, Mahmoudi, Saniyyah, Usitalo, Ann, Hayani, Karen, Rich, Kenneth, Richardson, Lourdes, Smith, Renee, Mitchell, Charles, Dominguez, Sady, Florez, Claudia, Frederick, Toni, Davtyan, Mariam, Morales-Avendano, Guadalupe, Rodriguez, Zoe M, Heyer, Ibet, Trifilio, Nydia Scalley, Scott, GB, Tuomala, R, Smith, E, Watts, H, Oden, KM, Huo, Y, Patel, K, Barr, EA, Bardeguez, A, Burchett, SK, Livingston, E, Stek, AM, Basar, MT, Hernandez, A, Jennings, A, Cressey, TR, Bryant, J, Tuomala, Ruth, Smith, Elizabeth, Oden, KaSaundra M, Leister, Erin, Shapiro, David E, Barr, Emily A, Wara, Diane W, Bardeguez, Arlene, and Guiterrez, Jenny

Subjects
Prevention, Pediatric Research Initiative, Clinical Research, Infant Mortality, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric, Infectious Diseases, Preterm, Low Birth Weight and Health of the Newborn, Reproductive health and childbirth, Good Health and Well Being, Adult, Birth Weight, CD4 Lymphocyte Count, Female, HIV Infections, Humans, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infectious Disease Transmission, Vertical, Male, Pregnancy, Pregnancy Complications, Infectious, Premature Birth, Prospective Studies, United States, Young Adult, Pediatric HIV/AIDS Cohort Study and the International Maternal Pediatric Adolescent AIDS Clinical Trials P1025 Protocol, Pediatric HIV/AIDS Cohort Study and the International Maternal Pediatric Adolescent AIDS Clinical Trials P1025 Protocol, birth weight, perinatal HIV infection, pregnancy, preterm delivery, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

BackgroundPregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined.MethodsWe compared preterm delivery and birth weight (BW) outcomes (low BW [LBW],

Published
2017

50. Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection: Associations with HIV disease severity, substance use, and cognition

Author

Angeles, C Paula Lewis-de los, Williams, Paige L, Huo, Yanling, Wang, Shirlene D, Uban, Kristina A, Herting, Megan M, Malee, Kathleen, Yogev, Ram, Csernansky, John G, Nichols, Sharon, Van Dyke, Russell B, Sowell, Elizabeth R, Wang, Lei, and Pediatric HIV/AIDS Cohort Study and the Pediatric Imaging, Neurocognition

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Mental Health, Pediatric, Brain Disorders, Drug Abuse (NIDA only), Substance Misuse, Neurosciences, Infectious Diseases, Clinical Research, HIV/AIDS, Pediatric AIDS, Biomedical Imaging, Behavioral and Social Science, Pediatric Research Initiative, Infection, Good Health and Well Being, Adolescent, Brain, Child, Cognition, Female, Gray Matter, HIV Infections, Humans, Infectious Disease Transmission, Vertical, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Organ Size, Severity of Illness Index, Substance-Related Disorders, Young Adult, Adolescence, Grey matter, HIV, Neuroimaging, Perinatally-acquired, Neuropsychology, Magnetic resonance imaging, Development, Pediatric HIV/AIDS Cohort Study (PHACS) and the Pediatric Imaging, Neurocognition, and Genetics (PING) Study, Immunology, Psychology, Neurology & Neurosurgery, Biological psychology
Abstract

Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age=16.7years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age=16.1years). PHIV youth had smaller (2.8-5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0-13.4%; marijuana use: 10.1-16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume.

Published
2017

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