RESUMO
INTRODUCTION: Over 265 000 women are living with HIV in the USA, but limited research has investigated the physical, mental and behavioural health outcomes among women living with HIV of reproductive age. Health status during the reproductive years before, during and after pregnancy affects pregnancy outcomes and long-term health. Understanding health outcomes among women living with HIV of reproductive age is of substantial public health importance, regardless of whether they experience pregnancy. The Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study is a prospective observational cohort study designed to investigate physical and mental health outcomes of young women living with HIV as they age, including HIV disease course, engagement in care, reproductive health and choices and cardiometabolic health. We describe the HOPE study design, and characteristics of the first 437 participants enrolled as of 1 January 2024. METHODS AND ANALYSIS: The HOPE study seeks to enrol and follow 1630 women living with HIV of reproductive age, including those with perinatally-acquired HIV, at 12 clinical sites across 9 US states and Puerto Rico. HOPE studies multilevel dynamic determinants influencing physical, mental and social well-being and behaviours of women living with HIV across the reproductive life course (preconception, pregnancy, post partum, not or never-pregnant), informed by the socioecological model. Key research areas include the clinical course of HIV, relationship of HIV and antiretroviral medications to reproductive health, pregnancy outcomes and comorbidities and the influence of racism and social determinants of health. HOPE began enrolling in April 2022. ETHICS AND DISSEMINATION: The HOPE study received approval from the Harvard Longwood Campus Institutional Review Board, the single institutional review board of record for all HOPE sites. Results will be disseminated through conference presentations, peer-reviewed journals and lay summaries.
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Infecções por HIV , Complicações Infecciosas na Gravidez , Humanos , Feminino , Gravidez , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , Adulto , Estados Unidos/epidemiologia , Adulto Jovem , Resultado da Gravidez , Projetos de Pesquisa , Antirretrovirais/uso terapêutico , Estudos Observacionais como Assunto , Adolescente , Saúde Mental , Saúde Reprodutiva , Fármacos Anti-HIV/uso terapêuticoRESUMO
OBJECTIVE: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF). DESIGN: IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study. METHODS: Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) more than 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIV pol/gag -DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair. RESULTS: Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. Nine of 18 (50%) were female sex-at-birth, and 14 of 18 (78%) were black. Median (range) age was 20âyears (13-27), time on ART was 18.3âyears (8.0-25.5), and FCCS was 68 (53-80). HIV-DNA was detected in PBMCs from all participants. In CSF, two of 18 (11%, 95% CI: 1.4-34.7%) participants had detectable cell-free HIV-RNA, while HIV gag or pol -DNA was detectable in 13 of 18 (72%, 95% confidence interval: 47-90). Detectable HIV-DNA in CSF was associated with male sex-at-birth ( P â=â0.051), lower CD4 + cell count at enrollment ( P â=â0.016), and higher PBMC HIV pol -DNA copies ( P â=â0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection. CONCLUSION: We found that a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.
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Antirretrovirais , DNA Viral , Infecções por HIV , RNA Viral , Humanos , Feminino , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Adolescente , DNA Viral/líquido cefalorraquidiano , Adulto Jovem , Adulto , RNA Viral/líquido cefalorraquidiano , Antirretrovirais/uso terapêutico , Prevalência , Disfunção Cognitiva , Estados Unidos/epidemiologia , Líquido Cefalorraquidiano/virologia , Biomarcadores/líquido cefalorraquidianoRESUMO
OBJECTIVE: Deficits in neurocognitive functioning are common among adolescents and young adults (AYA) with perinatally acquired HIV (PHIV). Limitations of traditional neuropsychological tests hinder assessment of neurocognition in low- and middle-income countries where most AYA with PHIV reside. Computerized testing could make assessment of neurocognition more accessible in these countries. This study examined a culturally modified NeuroScreen, a tablet-based neurocognitive testing app, for use in Thailand. Construct validity was examined among Thai AYA (13-23 years) with and without PHIV. METHOD: NeuroScreen underwent adaptation including language, content, and usability review by Thai psychologists, AYA, and clinical staff. One hundred Thai AYA (50 PHIV; 50 HIV-uninfected, matched controls) were administered the adapted NeuroScreen and a battery of traditional paper-and-pencil neuropsychological tests. Correlations, mean differences, and proportions with impaired performance were examined across NeuroScreen and the traditional tests. RESULTS: The Thai version of NeuroScreen was deemed understandable and culturally appropriate. A large correlation (.82) between overall performance on the NeuroScreen and traditional batteries was observed. Small-to-large correlations were found between conceptually similar NeuroScreen and traditional tests of processing speed, working memory, motor speed, and executive functioning. Mean test performance differences between AYA with PHIV and controls were similar between test batteries. Both sets of tests identified similar rates of impaired participants. CONCLUSIONS: Results provide support for the acceptability and construct validity of the Thai NeuroScreen tests to assess neurocognition in Thai AYA with PHIV. An easy-to-use tool to assess neurocognition can help Thai providers provide better care for AYA with PHIV. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Assuntos
Infecções por HIV , Adolescente , Adulto Jovem , Humanos , Tailândia , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/psicologia , Testes Neuropsicológicos , Função Executiva , CogniçãoRESUMO
This study examined associations of self-regulatory behavior and cognitive functioning with substance use (SU) to inform interventions for youth with perinatal HIV infection (YPHIV) or exposure but uninfected (YPHEU). Youth aged 7-15 years (YPHIV, n = 390; YPHEU, n = 211) were followed longitudinally with cognitive testing and behavioral questionnaires including self-report of alcohol, marijuana, tobacco, and other SU. Cox proportional hazards analyses were used to examine correlates of initiating each substance for those without prior use at baseline and generalized estimating equation analyses were used to address associations of cognitive/behavioral measurements with SU prevalence for the entire sample. Lower self-reported self-regulation skills, but higher cognitive functioning abilities, were associated with initiation and prevalent use of alcohol and marijuana regardless of HIV status. Our findings suggest SU screening tools and self-regulation interventions developed for general adolescent populations should be implemented for those with PHIV, who may be at heightened risk for SU-related health consequences.
RESUMEN: En este estudio se examina el vínculo del comportamiento autorregulado y la función cognoscitiva con el consumo de sustancias para argumentar intervenciones para los jóvenes con infección perinatal por el VIH (JIPVIH) y los jóvenes con exposición perinatal sin infección por el VIH (JEPSIVIH). Se hizo un seguimiento longitudinal de jóvenes de 7 a 15 años de edad (JIPVIH, n = 390; JEPSIVIH, n = 211) por medio de pruebas cognoscitivas y cuestionarios sobre el comportamiento, incluyendo el autoinforme de consumo de alcohol, marihuana, tabaco y otras sustancias. Se usaron los análisis Cox de riesgos proporcionales para examinar factores correlacionados con el inicio del consumo de cada sustancia por personas no consumidoras en el punto de referencia inicial. Asimismo, se usaron análisis de ecuaciones de estimación generalizadas para examinar la asociación entre la prevalencia del consumo de sustancias y las medidas cognoscitivas y las medidas conductuales para toda la muestra. Habilidades de autorregulación disminuidas, según autoinforme, pero capacidades superiores de función cognoscitiva, fueron vinculadas con el inicio y consumo frecuente de alcohol y marihuana, independientemente de la condición de VIH. Nuestros hallazgos sugieren que herramientas para detectar el consumo de sustancias e intervenciones de autorregulación creadas para la población general de adolescentes se deberían implementar para los JIPVIH que podrían correr mayores riesgos de sufrir consecuencias en la salud relacionadas con el consumo de sustancias.
Assuntos
Infecções por HIV , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Cognição , Feminino , Infecções por HIV/epidemiologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Testes Neuropsicológicos , Gravidez , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
OBJECTIVE: To develop a predictive model of neurocognitive trajectories in children with perinatal HIV (pHIV). DESIGN: Machine learning analysis of baseline and longitudinal predictors derived from clinical measures utilized in pediatric HIV. METHODS: Two hundred and eighty-five children (ages 2-14 years at baseline; Mageâ=â6.4 years) with pHIV in Southeast Asia underwent neurocognitive assessment at study enrollment and twice annually thereafter for an average of 5.4 years. Neurocognitive slopes were modeled to establish two subgroups [above (nâ=â145) and below average (nâ=â140) trajectories). Gradient-boosted multivariate regressions (GBM) with five-fold cross validation were conducted to examine baseline (pre-ART) and longitudinal predictive features derived from demographic, HIV disease, immune, mental health, and physical health indices (i.e. complete blood count [CBC]). RESULTS: The baseline GBM established a classifier of neurocognitive group designation with an average AUC of 79% built from HIV disease severity and immune markers. GBM analysis of longitudinal predictors with and without interactions improved the average AUC to 87 and 90%, respectively. Mental health problems and hematocrit levels also emerged as salient features in the longitudinal models, with novel interactions between mental health problems and both CD4 cell count and hematocrit levels. Average AUCs derived from each GBM model were higher than results obtained using logistic regression. CONCLUSION: Our findings support the feasibility of machine learning to identify children with pHIV at risk for suboptimal neurocognitive development. Results also suggest that interactions between HIV disease and mental health problems are early antecedents to neurocognitive difficulties in later childhood among youth with pHIV.
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Cognição/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Transmissão Vertical de Doenças Infecciosas , Aprendizado de Máquina , Desempenho Psicomotor/efeitos dos fármacos , Algoritmos , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Função Executiva/efeitos dos fármacos , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Saúde Mental , Parto , GravidezRESUMO
OBJECTIVES: Psychosocial challenges associated with perinatally acquired HIV (PHIV) infection are well known, yet many children infected with HIV since birth demonstrate positive outcomes, referred to as resilience. The purpose of this study was to evaluate emotional-behavioral development and identify salient predictors of resilience among long-term survivors of PHIV. DESIGN: Prospective investigation of children with PHIV compared with demographically similar perinatally HIV-exposed but uninfected (PHEU) and HIV-unexposed, uninfected (HUU) children, all from Thailand and Cambodia. METHODS: The Child Behavior Checklist (CBCL; parent version) was administered at baseline and annual follow-up visits (median follow-up of 3 years) to children age 6-14. Resilience was defined as consistent CBCL scores on the Internalizing, Externalizing or Total Problem T scales within normative ranges (T-scores <60) at every time point. Generalized estimating equations examined CBCL scores over time and logistic models examined demographic, socioeconomic, and cultural predictors of resilience. RESULTS: Participants included 448 children (236 PHIV, 98 PHEU, 114 HUU), with median (interquartile range) age at first evaluation of 7 (6-9) years. Children with PHIV exhibited similar rates of resilience as PHEU and HUU on the Externalizing and Total Problems scales. Resilience on the Internalizing scale was more likely in PHEU (71%) compared with PHIV (59%) or HUU (56%), Pâ=â0.049. Factors associated with resilience in adjusted models included: HIV-exposed but uninfected status, higher household income, Cambodian nationality, female sex, and caregiver type. CONCLUSION: Despite biopsychosocial risks, resilience is observed among PHIV and PHEU children. Further study is needed to understand mechanisms underlying associated factors and intervention priorities.
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Comportamento do Adolescente , Comportamento Infantil , Infecções por HIV/psicologia , Resiliência Psicológica , Adolescente , Camboja , Criança , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Modelos Logísticos , Masculino , Estudos Prospectivos , TailândiaRESUMO
BACKGROUND: Large numbers of perinatally HIV-infected (PHIV) children are aging into adolescence. We examined cognitive and behavioral outcomes in a longitudinal cohort of Asian youth. METHODS: We followed up 231 PHIV, 125 perinatally HIV-exposed, uninfected (HEU), and 138 HIV-unexposed, uninfected (HUU) adolescents (aged 10 years and older), matched by age/sex, in Thailand and Cambodia for 3 years. Executive function was assessed with Children's Color Trails Tests 1 and 2 (CCTT-1 and -2), the design fluency test, and the verbal fluency test. Working memory (Freedom from Distractibility Index) and processing speed index were assessed using WISC-III. Visual memory was assessed by design memory and design recognition subtests of the Wide Range Assessment of Memory and Learning (WRAML-2) and behavioral problems using the Child Behavior Checklist (CBCL). Generalized estimating equations examined adjusted odds ratios of cognitive impairment (Z-scores ≥2 SD below age-adjusted means of the HUU group) and CBCL T-scores in the borderline-clinical range (T-Scores ≥60) in PHIV and HEU versus HUU youth, adjusting for ethnicity, household income, and caregiver characteristics. RESULTS: The median age at enrollment was 13.8 years, with 58% women and 63% Thai participants. PHIV youth had >86% virological suppression and significantly higher impairment rates on CCTT-1 and -2 tests, design fluency test, verbal fluency tests, design memory, and CBCL internalizing and externalizing problems. Results were mostly similar between HEU and HUU groups, apart from higher impairment rates on CCTT-1 and internalizing problems in HEU. CONCLUSION: Asian adolescents with PHIV remain at risk of cognitive and mental health problems despite HIV treatment. Selective risks are observed among HEU youth.
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Comportamento do Adolescente , Comportamento Infantil , Função Executiva , Infecções por HIV/psicologia , Comportamento Problema , Adolescente , Camboja , Criança , Estudos de Coortes , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Aprendizagem , Masculino , Memória , Memória de Curto Prazo , TailândiaRESUMO
BACKGROUND: Medication adherence is a critical but challenging developmental task for children and adolescents with perinatally acquired HIV (PHIV). Understanding how medication responsibility, executive functions (EFs) and adaptive functioning (AF) influence adherence may help prepare adolescents for transition to adulthood. METHODS: Participants included PHIV children and adolescents 7-16 years of age enrolled in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, who were prescribed antiretroviral medications. Measures included caregiver report and child self-report measures of adherence, medication responsibility and EF, caregiver report of child AF, examiner-administered tests of EF and processing speed and demographic and health characteristics. RESULTS: Two hundred fifty-six participants with PHIV (mean age: 12 years old) were 51% female, 80% black and 79% non-Hispanic. Per 7-day recall, 72% were adherent (no missed doses). Children/adolescents self-reported that 22% had sole and 55% had shared medication responsibility. Adjusted logistic models revealed significantly higher odds of adherence with sole caregiver responsibility for medication [odds ratio (OR): 4.10, confidence interval (CI): 1.43-11.8, P = 0.009], child nadir CD4% <15% (OR: 2.26, CI: 1.15-4.43, P = 0.018), better self-reported behavioral regulation (OR: 0.65, CI: 0.44-0.96, P = 0.029) and slower processing speed (OR: 0.54, CI: 0.38-0.77, P < 0.001), adjusting for demographic variables (age, race and caregiver education). CONCLUSIONS: Among children and adolescents with PHIV, continued caregiver medication management, especially during adolescence, is essential. Although global EF and AF were not significantly associated with adherence, behavioral regulation was. Given that EF and AF develop throughout adolescence, their relationships to adherence should be evaluated longitudinally, especially as youth transition to adulthood and caregiver responsibility diminishes.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV , Adesão à Medicação , Adolescente , Cuidadores , Criança , Estudos de Coortes , Função Executiva , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Infecções por HIV/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricosRESUMO
BACKGROUND: Little is known regarding effects of perinatally acquired HIV infection (PHIV) on longitudinal change in memory and executive functioning (EF) during adolescence despite the importance of these skills for independence in adulthood. METHODS: PHIV (n = 144) and perinatally HIV-exposed uninfected youth (PHEU, n = 79), ages 12-17, completed standardized tests of memory and EF at baseline and 2 years later. Changes from baseline for each memory and EF outcome were compared between PHEU and PHIV youth with (PHIV/C, n = 39) and without (PHIV/non-C, n = 105) history of CDC class C (AIDS-defining) diagnoses. Among PHIV youth, associations of baseline and past disease severity with memory and EF performance at follow-up were evaluated using adjusted linear regression models. RESULTS: Participants were primarily black (79%); 16% were Hispanic; 55% were female. Mean memory and EF scores at follow-up generally fell in the low-average to average range. Pairwise comparison of adjusted mean change from baseline to follow-up revealed significantly greater change for PHIV/non-C compared with PHEU youth in only one verbal recognition task, with a difference in mean changes for PHIV/non-C versus PHEU of -0.99 (95% CI: -1.80 to -0.19; P = 0.02). Among youth with PHIV, better immunologic status at baseline was positively associated with follow-up measures of verbal recall and recognition and cognitive inhibition/flexibility. Past AIDS-defining diagnoses and higher peak viral load were associated with lower performance across multiple EF tasks at follow-up. CONCLUSIONS: Youth with PHIV demonstrated stable memory and EF during a 2-year period of adolescence, allowing cautious optimism regarding long-term outcomes.
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Função Executiva/fisiologia , Infecções por HIV/congênito , Infecções por HIV/psicologia , Transmissão Vertical de Doenças Infecciosas , Memória/fisiologia , Adolescente , Criança , Feminino , Infecções por HIV/fisiopatologia , Humanos , Deficiências da Aprendizagem/fisiopatologia , Masculino , Transtornos da Memória/fisiopatologia , Testes Neuropsicológicos , Estudos Prospectivos , Estados Unidos , Carga ViralRESUMO
Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth, we evaluated the contributions of home environment, psychosocial, and demographic factors and, among PHIV only, HIV disease severity and antiretroviral treatment (ART), to cognitive functioning (CF) and behavioral functioning (BF). A structural equation modeling (SEM) approach was utilized. Exploratory factor analysis was used to reduce predictor variables to major latent factors. SEMs were developed to measure associations between the latent factors and CF and BF outcomes. Participants included 231 PHIV and 151 PHEU youth (mean age = 10.9 years) enrolled in the PHACS adolescent master protocol. Youth and caregivers completed assessments of CF, BF, psychosocial factors and HIV health. Medical data were also collected. Clusters of predictors were identified, establishing four parsimonious SEMs: child-assessed and caregiver-assessed BF in PHIV and PHEU youth. Among both groups, higher caregiver-child stress predicted worse BF. Caregiver resources and two disease severity variables, late presenter and better past HIV health, were significant predictors of CF in PHIV youth. Higher youth CF was associated with better caregiver-reported BF in both groups. Caregiver resources predicted caregiver-reported BF in PHEU youth, which was mediated via youth CF. Among PHIV youth, better past HIV health and caregiver resources mediated the effects of CF on caregiver-assessed BF. Using SEMs, we found a deleterious impact of caregiver and child stress on BF in both groups and of HIV disease factors on the CF of PHIV youth, reinforcing the importance of early comprehensive intervention to reduce risks for impairment.
Assuntos
Comportamento do Adolescente , Cuidadores/psicologia , Cognição/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Criança , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Adesão à Medicação , Gravidez , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Executive functions (EFs) are critical for management of life activities, but few studies have evaluated EFs in children and adolescents with perinatally acquired HIV (PHIV), who are at risk for problems in academics, behavior, and medication adherence. We compared EFs in youth with PHIV and in perinatally HIV-exposed but uninfected (PHEU) youth. METHODS: Four Delis-Kaplan Executive Function System (D-KEFS) subtests were administered to 173 youth with PHIV and 85 PHEU youth, aged 9 to <19 years, who were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Memory and Executive Functioning Study. Youth with PHIV, with or without history of a Centers for Disease Control and Prevention Class C (AIDS-defining) condition (PHIV/C [n = 45] and PHIV/non-C [n = 128], respectively), were compared with each other and with PHEU youth. Among youth with PHIV, associations with measures of current and past disease severity were evaluated using adjusted linear regression models. RESULTS: The PHIV/C group (mean age, 15.5 years), compared with the PHIV/non-C and PHEU groups (mean ages, 14.5 and 12.9 years, respectively), were significantly slower on the Inhibition and Color Naming/Reading Combined conditions of the Color-Word Interference subtest and made more errors on Inhibition; differences between the PHIV/C and PHEU groups persisted in adjusted models. No differences in adjusted means for fluency or problem-solving were found. The PHIV/non-C and PHEU groups did not differ on any measure. Associations of specific EF measures with HIV RNA viral load, CD4-positive T-lymphocyte percentage, and age at greatest disease severity were observed. CONCLUSIONS: Youth with PHIV and previous AIDS-defining conditions performed more poorly on some EF measures. Relationships of EF development with the degree and timing of disease severity require further study. Implications for long-term outcomes and interventions are important avenues for follow-up.
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Função Executiva , Infecções por HIV/fisiopatologia , Infecções por HIV/psicologia , Adolescente , Criança , Feminino , Infecções por HIV/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Testes NeuropsicológicosRESUMO
BACKGROUND: Perinatally acquired HIV (PHIV) confers risk for neurocognitive impairment, which potentially affects school performance and functional independence of infected children. In this study, we examined the associations of 2 key neurocognitive domains, memory and executive function (EF), with academic and adaptive skills among youth with PHIV and perinatally HIV-exposed but uninfected (PHEU) youth. METHODS: Participants ages 9 to <19 years enrolled in the Pediatric HIV/AIDS Cohort Study's Memory and Executive Functioning Study completed standardized measures of reading and math. The primary caregivers completed a standardized measure of their child's adaptive behavior. Participants with PHIV, those with (PHIV/C) and without (PHIV/non-C) a Centers for Disease Control and Prevention class C diagnosis, and PHEU participants were compared. Retrospective memory (RM), prospective memory (PM), and EF were evaluated relative to outcomes using general linear regression models adjusted for sociodemographic characteristics. RESULTS: Of the participants (N = 258; mean age, 14.1 years), 46% were male, 75% were black, and 18% were Hispanic. Adjusted mean scores in math and adaptive behavior did not differ among the youth with PHIV/C (n = 45), those with PHIV/non-C (n = 128), and PHEU youth (n = 85). Youth with PHIV/C had lower adjusted mean reading scores than PHIV/non-C and PHEU youth (86.9 vs 93.8 [P = .02] and 93.2 [P = .04], respectively). There were positive associations of RM, PM, EF, and some sociodemographic characteristics with higher reading and math scores. Immediate and delayed verbal memory, delayed visual memory, PM, and some EF measures were positively associated with adaptive behavior. CONCLUSIONS: Higher-order cognitive abilities such as memory and EF seem to play a key role in academic and adaptive capacities, regardless of a child's HIV status, and might serve as intervention targets for improving functional outcomes.
Assuntos
Função Executiva , Infecções por HIV/fisiopatologia , Infecções por HIV/psicologia , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Adaptação Psicológica , Adolescente , Criança , Feminino , Infecções por HIV/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Testes NeuropsicológicosRESUMO
BACKGROUND: Perinatal HIV (PHIV) infection may place youth at risk for impairments in executive functioning (EF). We examined associations of EF with HIV infection, disease severity and other factors among youth with PHIV and perinatally HIV-exposed, uninfected youth (PHEU). METHODS: Within the US-based Pediatric HIV/AIDS Cohort Study, 354 PHIV and 200 PHEU youth completed a standardized EF measure (Children's Color Trails Test, CCTT) and youth and/or caregivers completed a questionnaire measuring everyday EF (Behavior Rating Inventory of Executive Function, BRIEF). Covariates included HIV status, current and historical disease severity, demographic and caregiver variables and other cognitive measures. Analyses used linear and logistic regression and proportional odds models. RESULTS: No significant HIV status group differences were found on CCTT scores. Caregiver BRIEF ratings indicated significantly fewer problems for PHIV than PHEU youth. However, PHIV youth with past encephalopathy self-endorsed significantly greater metacognitive (ie, cognitive regulation) problems on the BRIEF and performed more slowly on the CCTT than PHEU youth. CCTT and caregiver BRIEF scores had significant associations with indicators of past and present disease severity. Both PHIV and PHEU had significantly worse scores than population means on CCTT and BRIEF; scores had significant associations with demographic covariates. CONCLUSIONS: Youth with PHIV show EF problems likely associated with risk factors other than HIV. However, cognitive slowing and self-reported metacognitive problems were evident in PHIV youth with a history of encephalopathy. Assessment and treatment of EF impairment may be important to identifying PHIV youth at particular risk for poor health and behavioral outcomes.
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Função Executiva , Infecções por HIV/patologia , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Prospectivos , Estados UnidosRESUMO
INTRODUCTION: Adolescents are a unique and sometimes neglected group in the planning of healthcare services. This is the case in many parts of sub-Saharan Africa, where more than eight out of ten of the world's HIV-infected adolescents live. Although the last decade has seen a reduction in AIDS-related mortality worldwide, largely due to improved access to effective antiretroviral therapy (ART), AIDS remains a significant contributor to adolescent mortality in sub-Saharan Africa. Although inadequate access to ART in parts of the subcontinent may be implicated, research among youth with HIV elsewhere in the world suggests that suboptimal adherence to ART may play a significant role. In this article, we summarize the epidemiology of HIV among sub-Saharan African adolescents and review their adherence to ART, emphasizing the unique challenges and factors associated with adherence behaviour. METHODS: We conducted a comprehensive search of online databases for articles, relevant abstracts, and conference reports from meetings held between 2010 and 2014. Our search terms included "adherence," "compliance," "antiretroviral use" and "antiretroviral adherence," in combination with "adolescents," "youth," "HIV," "Africa," "interventions" and the MeSH term "Africa South of the Sahara." Of 19,537 articles and abstracts identified, 215 met inclusion criteria, and 148 were reviewed. DISCUSSION: Adolescents comprise a substantial portion of the population in many sub-Saharan African countries. They are at particular risk of HIV and may experience worse outcomes. Although demonstrated to have unique challenges, there is a dearth of comprehensive health services for adolescents, especially for those with HIV in sub-Saharan Africa. ART adherence is poorer among older adolescents than other age groups, and psychosocial, socio-economic, individual, and treatment-related factors influence adherence behaviour among adolescents in this region. With the exception of a few examples based on affective, cognitive, and behavioural strategies, most adherence interventions have been targeted at adults with HIV. CONCLUSIONS: Although higher levels of ART adherence have been reported in sub-Saharan Africa than in other well-resourced settings, adolescents in the region may have poorer adherence patterns. There is substantial need for interventions to improve adherence in this unique population.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Adesão à Medicação , Adolescente , África Subsaariana/epidemiologia , Criança , Pré-Escolar , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Masculino , África do Sul , Adulto JovemRESUMO
OBJECTIVES: We investigated whether HIV disease severity was associated with alterations in structural brain connectivity, and whether those alterations in turn were associated with cognitive deficits in youth with perinatally acquired HIV (PHIV). DESIGN: PHIV youth (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) (mean age: 16â±â2 years) were included to evaluate how current and past disease severity measures (recent/nadir CD4%; peak viral load) relate to white matter microstructure within PHIV youth. PHIV youth were compared with 314 controls from the Pediatric Imaging, Neurocognition and Genetics (PING) study. METHODS: Diffusion tensor imaging and tractography were utilized to assess white matter microstructure. Mediation analyses were conducted to examine whether microstructure alterations contributed to relationships between higher disease severity and specific cognitive domains in PHIV youth. RESULTS: Whole brain fractional anisotropy was reduced, but radial and mean diffusivity were increased in PHIV compared with control youth. Within PHIV youth, more severe past HIV disease was associated with reduced fractional anisotropy of the right inferior fronto-occipital (IFO) and left uncinate tracts; elevated mean diffusivity of the F minor; and increased streamlines comprising the left inferior longitudinal fasciculus (ILF). Associations of higher peak viral load with lower working memory performance were partly mediated by reductions in right IFO fractional anisotropy levels. CONCLUSION: Our findings suggest that PHIV youth have a higher risk of alterations in white matter microstructure than typically developing youth, and certain alterations are related to past disease severity. Further, white matter alterations potentially mediate associations between HIV disease and working memory.
Assuntos
Infecções por HIV/patologia , Índice de Gravidade de Doença , Substância Branca/patologia , Adolescente , Contagem de Linfócito CD4 , Criança , Transtornos Cognitivos/epidemiologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Estudos Prospectivos , Radiografia , Carga Viral , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: To estimate the association of age of viral suppression and central nervous system penetration effectiveness (CPE) score with neurocognitive functioning among school-age children with perinatally acquired HIV infection (PHIV+). DESIGN: We analyzed data from two US-based multisite prospective cohort studies. METHODS: Multivariable general linear regression models were used to evaluate associations of age at viral suppression and CPE scores (of initial antiretroviral therapy regimen and weighted average) with the Wechsler Intelligence Scale for Children, Third or Fourth Edition neurocognitive assessments [Full-Scale Intelligence Quotient (FSIQ); Performance IQ/Perceptual Reasoning Index (PIQ/PRI); and Verbal IQ/Verbal Comprehension Index (VIQ/VCI)], adjusted for demographic and clinical covariates. Sensitivity analyses were stratified by birth cohort (before versus after 1996). RESULTS: A total of 396 PHIV+ children were included. Estimated differences in mean FSIQ (comparing virally suppressed versus unsuppressed children) by each age cutoff were 3.7, 2.2, 3.2, 4.4, and 3.9 points at ages 1, 2, 3, 4, and 5, respectively. For PIQ/PRI, estimated mean differences were 3.7, 2.4, 2.2, 4.6, and 4.5 at ages 1 through 5, respectively. In both cases, these differences were significant only at the age 4 and 5 thresholds. After stratifying by birth cohort, the association between age at suppression and cognitive function persisted only among those born after 1996. Age at viral suppression was not associated with VIQ/VCI; CPE score was not associated with FSIQ, verbal comprehension, or perceptual reasoning indices. CONCLUSION: Virologic suppression during infancy or early childhood is associated with improved neurocognitive outcomes in school-aged PHIV+ children. In contrast, CPE scores showed no association with neurocognitive outcomes.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Síndromes Neurocutâneas/prevenção & controle , Prevenção Secundária/métodos , Carga Viral , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Infecções por HIV/virologia , Humanos , Lactente , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
The prevalence of HIV-associated neurocognitive impairment in perinatally HIV-infected children has declined since the introduction of combination antiretroviral therapy (cART). Early initiation of cART in infancy has been shown to positively impact neurodevelopment; however, children continue to be diagnosed with HIV outside of the early infancy period and can experience subtle to severe neurocognitive deficits despite cART. The causes of these neurocognitive deficits despite effective cART are multifactorial and likely include continued viral replication in the CNS, ongoing neuroinflammation, irreversible CNS injury prior to cART initiation, neurotoxic effects of cART, and socioeconomic and psychosocial effects. Many aspects of our understanding of HIV-associated neurocognitive disorders have emerged from research in adult patients, but perinatally HIV-infected children represent a very different population. These children were exposed to HIV during a period of rapid brain development and have lifelong infection and potential lifelong cART exposure. HIV is no longer a rapidly fatal disease, and most HIV-infected children in resource-rich countries are living into adulthood. It is therefore critical to optimize neurocognitive outcomes of these youth. This review summarizes current understanding of the pathogenesis of HIV-associated CNS infection and the impact of cART on neurocognitive function in children and adolescents and discusses important areas for future research.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/virologiaRESUMO
OBJECTIVE: To evaluate prevalence, incidence, remission, and persistence of psychiatric and substance use disorders among HIV-infected mothers and identify biopsychosocial correlates. METHODS: HIV-infected mothers (n = 1223) of HIV-exposed uninfected children enrolled in a prospective cohort study; HIV-uninfected mothers (n = 128) served as a comparison group. Mothers provided sociodemographic and health information and completed the Client Diagnostic Questionnaire (CDQ). Prevalence of any psychiatric or substance use disorder at initial evaluation was compared between the 2 groups. Incident, remitting, and persisting disorders were identified for 689 mothers with HIV who completed follow-up CDQs. We used logistic regression to evaluate adjusted associations of biopsychosocial characteristics with presence, incidence, remission, and persistence of disorders. RESULTS: Thirty-five percent of mothers screened positive for any psychiatric or substance use disorder at initial evaluation, with no difference by maternal HIV status (P = 1.00). Among HIV-infected mothers, presence of any disorder was associated with younger age [adjusted odds ratio (aOR): 1.39; 95% CI: 1.09 to 1.75], single parenthood (aOR: 1.35; 95% CI: 1.08 to 1.68), and functional limitations (aOR: 2.29; 95% CI: 1.81 to 2.90). Incident disorders were associated with functional limitations (aOR: 1.92; 95% CI: 1.10 to 3.30). Among HIV-infected mothers with a disorder at initial evaluation (n = 238), 61% had persistent disorders. Persistent disorders were associated with lower income (aOR: 2.44; 95% CI: 1.33 to 4.76) and functional limitations (aOR: 3.19; 95% CI: 1.87 to 5.48). Receipt of treatment for any disorder was limited: 4.5% at study entry, 7% at follow-up, 5.5% at both entry and follow-up. CONCLUSIONS: Psychiatric and substance use disorders remain significant comorbid conditions among HIV-infected mothers and require accessible evidence-informed treatment.