Perinatally HIV-exposed But Uninfected Research Articles

Hope for the future protects against suicidal ideation among adolescents and young adults affected by perinatal HIV

ABSTRACT Hope for the future has been found protective against suicidal ideation (SI) in adolescents and young adults (AYA) yet has not been examined in AYA with perinatal HIV-infection (PHIV) or AYA who were perinatally HIV-exposed but uninfected (PHEU), who are at higher risk for SI than general populations. Using data from a New York City-based longitudinal study of AYAPHIV and AYAPHEU enrolled when 9–16 years old, we examined associations between hope for the future, psychiatric disorders, and SI over time using validated measures. Generalized estimating equations were used to estimate differences in mean hope for the future scores by PHIV-status and to estimate adjusted odds ratios for associations between hope for the future and SI. AYA reported high hope for the future scores and low SI across visits, irrespective of PHIV-status. Higher hope for the future scores were associated with lower odds of SI (AOR = 0.48, 95% CI: 0.23, 0.996). Mood disorder was associated with increased odds of SI (AOR = 13.57, 95% CI: 5.11, 36.05) in a model including age, sex, follow-up, PHIV-status, mood disorder, and hope for the future. Understanding how hope can be cultivated and how it protects against SI can help to inform preventive interventions for HIV-affected AYA.

Psychiatric, behavioral and emotional disorders in Polish children and adolescents with perinatal HIV infection.

The aims of the study were to evaluate the prevalence of psychiatric, behavioral and emotional disorders in children and adolescents with perinatal HIV infection and to establish their possible relationships with clinical and sociodemographic variables. 56 children with perinatal HIV infection (PHIV+ group), 24 healthy children perinatally HIV-exposed but uninfected (PHEU) and 43 healthy children of uninfected parents (HIV-nA), aged 6-18 years, were assessed. The Child Behavior Checklist (CBCL/4-18), completed by parents, and the Youth Self-Report (YSR) were used to assess behavioral and emotional disorders, while the semi-structured diagnostic interview K-SADS-PL was used to assess the symptoms of psychiatric disorders. Higher prevalence of psychiatric disorders was found in the PHIV+ group and the PHEU group compared to the HIV-nAgroup. Anxiety disorders and affective disorders were diagnosed most often. Prevalence of symptoms of emotional and behavioral disorders in the PHIV+ group and in the PHEU group was associated with similar sociodemographic variables (male, not living with the biological caregiver, the experience of stressful life events). Psychiatric disorders were noted more often among PHIV+ subjects whose ARV treatment was started after 12 months of age. Positive correlations were observed between the results of some YSR and CBCL/4-18 problem scales and CD4 counts at the time of the study, higher logarithm of viral load at the start of ARV treatment and at the time of HIV diagnosis. The prevalence of psychiatric disorders in PHIV+ group and the PHEU group is higher in comparison with HIV-nAgroup. Amore serious course of HIV infection and its severity before treatment are associated with the severity of internalizing problems.

Health-related quality of life in Polish children and adolescents with perinatal HIV infection – short report

ABSTRACT The aims of the study were to assess health-related quality of life (HRQoL) in children and adolescents with perinatal HIV infection and to establish possible relationships with clinical and socio-demographic variables. About 56 children with perinatal HIV infection, aged 6–18 years (PHIV+ group), 24 healthy perinatally HIV-exposed but uninfected (PHEU) children, and 43 children HIV-unexposed uninfected (HUU) were assessed using the PedsQL 4.0. Generic Core. The perceptions of school functioning according to children and social functioning, according to parents, were worse in the PHIV+ group compared to those in the PHEU group. In comparison to the HUU group, PHIV+ children received lower total HRQoL scores in the caregivers’ perception. Most of the life-quality indices increased systematically with age in PHIV+ group, whereas opposite trends were present in both control groups. Caregivers of children with a final CDC category C and caregivers of children diagnosed with encephalopathy perceived most domains of their children functioning as more problematic. A more serious course and more severe HIV infection before treatment were associated with worse multidimensional functioning and a worse total HRQoL score. Results highlight the importance of early diagnosis and treatment initiation as having significant implications for the quality of life.

Emotional and behavioral resilience among children with perinatally acquired HIV in Thailand and Cambodia.

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. 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. 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. 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%), P = 0.049. Factors associated with resilience in adjusted models included: HIV-exposed but uninfected status, higher household income, Cambodian nationality, female sex, and caregiver type. Despite biopsychosocial risks, resilience is observed among PHIV and PHEU children. Further study is needed to understand mechanisms underlying associated factors and intervention priorities.

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

Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth. The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites. Among 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. Among 485 participants (305 PHIV and 180 PHEU) with echocardiograms and bone mineralization measures, low 25-OHD (<20 ng/mL) was common among all participants (48% PHIV and 44% PHEU), but elevated PTH (>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. In 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.

Caregiver perceptions of environment moderate relationship between neighborhood characteristics and language skills among youth living with perinatal HIV and uninfected youth exposed to HIV in New York City

ABSTRACTDespite the increased recognition of how neighborhood conditions bear on cognitive and academic outcomes, no studies have examined the influences of objective and subjective neighborhood indices on specific areas of cognitive functioning among youth living with perinatal HIV (PHIV). In the United States (US), this is of particular concern as HIV has disproportionately affected African American youth living in economically disadvantaged and racially segregated communities. Thus, based on a longitudinal cohort study of psychosocial and behavioral health outcomes in 340 perinatally HIV-exposed but uninfected (PHEU) and PHIV youth residing in New York City, ages 9–16 years at enrollment, we analyzed data from baseline and multiple follow-up (FU) quantitative interviews with youth and their primary caregivers, from when they were at least 13-years-old (approximately 4–6 years post enrollment). We examined the association between baseline neighborhood indices (2000 US census data and caregiver’s perception of neighborhood stressors) and youth receptive language skills (PPVT; Peabody Picture Vocabulary Test) at FU2 and FU3. Census data (percentage of families in neighborhood living below the national poverty rate, median neighborhood household income, and percentage of residents professionally employed) were not independently associated with PPVT scores at both follow-ups. However, in the logistic regression model, the more caregivers perceived their neighborhood as stressful and subjected to violence, the stronger the relationship between census data indicators of low resource neighborhoods and lower PPVT scores for both groups. Findings support “place-based” policies and practices that alleviate caregiver experiences of neighborhood stressors which may contribute to improved cognitive outcomes for youth living with and affected by PHIV.

Prospective memory in youth with perinatally-acquired HIV infection

ABSTRACTYouth with perinatal HIV infection (PHIV) are at increased risk for neurocognitive impairment (NCI). Prospective memory (PM) is a complex neurocognitive function that has been shown to be impaired in adults with HIV disease and independently associated with poorer daily living skills, including medication nonadherence. The current study sought to determine the presence and extent of PM deficits in youth with PHIV. Participants included 173 youth with PHIV and 85 youth perinatally HIV-exposed but uninfected (PHEU), mean age 14.1 years, 75% black, 18% Hispanic. Among youth with PHIV, 26% had a past AIDS-defining condition (Centers for Disease Control and Prevention [CDC], Class C), 74% did not (non-C). Adjusted generalized estimating equation models were used to compare groups (PHIV/C, PHIV/non-C, and PHEU) on the Naturalistic Event-Based Prospective Memory Test (NEPT) and the Prospective Memory Assessment for Children & Youth (PROMACY). Secondarily, subgroups defined by HIV serostatus and global NCI were compared (PHIV/NCI, PHIV/non-NCI, PHEU). PHIV/C had significantly lower NEPT scores than PHEU, with decreases of 40% in mean scores, but did not differ from PHIV/non-C. PHIV/NCI had 11–32% lower PROMACY scores and 33% lower NEPT scores compared to PHIV/non-NCI (all p < .05); significantly, lower scores for PHIV/NCI versus PHEU also were observed for PROMACY and NEPT indices. Findings suggest a subset of youth with PHIV (those with a prior AIDS-defining diagnosis) is vulnerable to PM deficits. The extent to which PM deficits interfere with development and maintenance of independent living and health-related behaviors during transition to adulthood requires further study.

Executive Functioning in Children and Adolescents With Perinatal HIV Infection and Perinatal HIV Exposure.

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. 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. 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. 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.

Associations of Memory and Executive Functioning With Academic and Adaptive Functioning Among Youth With Perinatal HIV Exposure and/or Infection.

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. 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. 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. 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.

A Prospective Longitudinal Study of Mental Health Symptoms Among Perinatally HIV-Infected and HIV-Exposed but Uninfected Urban Youths

PurposeSignificant gaps persist in our understanding of the etiological factors that shape the progression of mental health symptoms (MHS) among perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youths. This study sought to assess the changes in MHS among PHIV+ and PHEU youths as they transition through adolescence and to identify the associated psychosocial factors. MethodsData were drawn from a longitudinal study of 166 PHIV+ and 114 PHEU youths (49% male, ages 9–16 years at baseline) in New York City. Individual interviews were administered at baseline and subsequently over a 5-year period. MHS were assessed using the youth version of the Diagnostic Interview Schedule for Children. Predictive growth curve analyses were conducted to assess longitudinal changes in MHS and identify the relevant factors. Level I predictors included: time, major life events, household poverty, caregiver mental health, and neighborhood stressors. Level II predictors included youths' sociodemographic characteristics (e.g., age, gender, HIV status) and baseline future orientation scores. ResultsThe changes in youths' MHS followed a quadratic growth curve and were positively associated with the number of major negative life events and neighborhood stressors experienced. Youths' HIV status, household poverty, and caregiver mental health were not significantly associated with youths' MHS. ConclusionsFindings suggest that irrespective of youths' HIV status, major life events and neighborhood stressors increase MHS among PHIV+ and PHEU youths. There is a need for interventions to reduce the impact of stressors on the mental well-being of PHIV+ and PHEU youths.

Prevalence and Persistence of Varicella Antibodies in Previously Immunized Children and Youth With Perinatal HIV-1 Infection.

Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥ 15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status. The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites. In a cross-sectional analysis, we tested participants' most recent stored sera for varicella antibody using whole-cell and glycoprotein enzyme-linked immunosorbent assay. Seropositivity predictors were identified using multivariable logistic regression models and C statistics. Samples were available for 432 children with PHIV and 221 PHEU children; 82% of children with PHIV and 97% of PHEU children were seropositive (P < .001). Seropositivity after 1 vaccine dose among children with PHIV and PHEU children was 100% at <3 years (both), 73% and 100% at 3-<7 years (P < .05), and 77% and 97% at ≥ 7 years (P < .01), respectively. Seropositivity among recipients of 2 vaccine doses was >94% at all intervals. Independent predictors of seropositivity among children with PHIV were receipt of 2 vaccine doses, receipt of 1 dose while on ≥ 3 months of cART, compared with none (adjusted odds ratio [aOR]: 14.0 and 2.8, respectively; P < .001 for overall dose effect), and in those vaccinated ≥ 3 years previously, duration of cART (aOR: 1.29 per year increase, P = .02). Humoral immune responses to varicella vaccine are best achieved when children with PHIV receive their first dose ≥ 3 months after cART initiation and maintained by completion of the 2-dose series and long-term cART use.

Biomarkers and neurodevelopment in perinatally HIV-infected or exposed youth

To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth. Cross-sectional design within a prospective, 15-site US-based cohort study. Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores. Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs. Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth.

Mental health functioning among children and adolescents with perinatal HIV infection and perinatal HIV exposure

Mental health problems (MHPs) among children with perinatal HIV infection have been described prior to and during the highly active antiretroviral therapy (HAART) era. Yet child, caregiver and socio-demographic factors associated with MHPs are not fully understood. We examined the prevalence of MHPs among older children and adolescents with perinatal HIV exposure, including both perinatally HIV-infected (PHIV + ) and perinatally HIV-exposed but uninfected (PHEU) youth. Our aims were to identify the impact of HIV infection by comparing PHIV+ and PHEU youth and to delineate risk factors associated with MHPs, in order to inform development of appropriate prevention and intervention strategies. Youth and their caregivers were interviewed with the Behavior Assessment System for Children, 2nd edition (BASC-2) to estimate rates of at-risk and clinically significant MHPs, including caregiver-reported behavioral problems and youth-reported emotional problems. The prevalence of MHPs at the time of study entry was calculated for the group overall, as well as by HIV status and by demographic, child health, and caregiver characteristics. Logistic regression models were used to identify factors associated with youth MHPs. Among 416 youth enrolled between March 2007 and July 2009 (295 PHIV+, 121 PHEU), the overall prevalence of MHPs at entry was 29% and greater than expected based on recent national surveys of the general population. MHPs were more likely among PHEU than among PHIV+ children (38% versus 25%, p<0.01). Factors associated with higher odds of MHPs at p<0.10 included caregiver characteristics (psychiatric disorder, limit-setting problems, health-related functional limitations) and child characteristics (younger age and lower IQ). These findings suggest that PHEU children are at high risk for MHPs, yet current models of care for these youth may not support early diagnosis and treatment. Family-based prevention and intervention programs for HIV affected youth and their caregivers may minimize long-term consequences of MHPs.