Background:Mental health outcomes are substantially poorer among people with HIV than the general population. We investigated whether inflammation or HIV status may play a role in the longitudinal trajectories of depressive symptoms. Methods:This prospective cohort study involved 862 children (291 without HIV, 292 exposed to HIV, 279 with HIV) and 439 adult caregivers (165 without HIV, 274 with HIV) recruited from 2017 to 2024 from the Kawaala Health Center IV in Kampala, Uganda. High-sensitivity C-Reactive Protein (CRP) was measured in blood serum at baseline using ELISA. Depressive symptoms were assessed longitudinally using the Patient Health Questionnaire (PHQ-9) at six-monthly intervals for up to 24 months (total 3212 observations), with 2% of children and 4% of adults meeting criteria for severe depressive symptoms (PHQ-9 score > 10) at baseline. Latent growth curve modelling was used to investigate interactions between HIV status and CRP concentration on the baseline (intercept) and longitudinal change (slope) of PHQ-9 scores, separately for children and adults. Results:Here we show that the association of baseline CRP concentrations with the intercept (β [95% confidence interval] = -0.09 [-0.18, -0.01], p = 0.034) and slope (β = 0.09 [0.03, 0.15], p = 0.004) of PHQ-9 score trajectories varied significantly according to HIV status among children. At higher baseline CRP concentrations, children with HIV showed lower baseline depressive symptoms relative to children without HIV. Over time, depressive symptoms increased in children with HIV but decreased in children without HIV. No differences in trajectories were observed in adults. Conclusions:Our results suggest that given high baseline inflammation, recovery from depressive symptoms may be significantly slower among children living with HIV compared to those without HIV. Specific interventions to reduce inflammation may need to be combined with more regular, holistic and personalised interventions to alleviate depressive symptoms among children with HIV.

Fatty acids (FAs) play critical neurodevelopmental roles, yet associations with executive function among children affected by perinatal HIV remain poorly characterized. This prospective cohort study examined associations between serum FAs and caregiver-reported executive function and evaluated effect modification by perinatal HIV status among 6-10-year-old Ugandan children who had perinatal HIV infection (CPHIV; n = 84), were HIV exposed but uninfected (CHEU; n = 78), or were HIV unexposed and uninfected (CHUU; n = 81). Serum FAs were measured at enrollment, and executive dysfunction was assessed at enrollment, 6, and 12 months (Executive Functioning Index (EFI) and Global Executive Composite (GEC)). Multivariable linear mixed models estimated overall and HIV-specific mean differences (MDs) and 95% confidence intervals (CIs) in executive dysfunction z-scores by FA tertiles. Moderate versus low arachidonic acid (MD [95% CI] EFI: -0.40 [-0.71, -0.09]; GEC: -0.30 [-0.58, -0.03]) and highly unsaturated FAs (HUFAs; EFI: -0.41 [-0.72, -0.11]) associated with lower executive dysfunction. Among CPHIV, high Mead acid (20:3 (n-9)) associated with higher executive dysfunction (EFI: 0.56 [0.11, 1.01]). Among CHEU, lower executive function was associated with high docosatetraenoic acid (EFI: -0.93 [-1.71, -0.15]) and docosahexaenoic acid (GEC: -0.78 [-1.26, -0.31]). These results showed that higher HUFAs associated with better executive function, particularly among CHEU, supporting further nutritional intervention research for children affected by perinatal HIV.

BACKGROUND:Associations between fatty acids (FAs) and scholastic outcomes in adolescents are understudied. These relationships may be especially important in adolescents with perinatal HIV exposure or infection who are more vulnerable to FA insufficiency and educational disruption. OBJECTIVES:To evaluate associations between baseline FAs, including essential FA deficiency (EFAD), and scholastic outcomes >18 mo, and to assess heterogeneity by perinatal HIV status among Ugandan adolescents. METHODS:Adolescents (n = 373) were followed for 18 mo. Baseline serum FAs, including the triene:tetraene (T:T) ratio, were categorized into tertiles ("low," "moderate," and "high"). Scholastic outcomes were assessed every 6 mo via questionnaires. Self-report scholastic disadvantage, school aversion, and teacher challenge were age- and sex-standardized to z-scores; grade repetition, nonenrollment, and morbidity-related educational loss were dichotomous. Time-averaged mean differences (MDs) or odds ratios (ORs) and 95% confidence intervals (CIs) were measured using adjusted linear mixed-effects models or generalized estimating equations. FA × HIV interactions assessed heterogeneity by perinatal HIV status. RESULTS:Moderate compared with low total omega (ω)-3 polyunsaturated FAs (PUFAs) were associated with lower teacher challenge [MD (95% CI): -0.27 (-0.47, -0.07)], whereas a higher ω-6:ω-3 ratio was associated with greater teacher challenge [0.30 (0.07, 0.52)]. Contrary to hypotheses, a high compared with low T:T ratio was associated with lower school aversion [-0.36 (-0.73, 0.00)] and nonenrollment OR [OR (95% CI): 0.57 (0.35, 0.94)]. High mead acid concentrations, however, correlated with higher odds of morbidity-related educational loss [2.48 (1.01, 6.15)]. Associations were more consistent for standardized z-score outcomes than dichotomous outcomes. When heterogeneity was present, associations differed by HIV status, with patterns varying across outcomes. CONCLUSIONS:ω-3 PUFAs and the ω-6:ω-3 ratio were more consistently associated with scholastic outcomes than EFAD markers, highlighting the importance of ω-3 PUFA status among adolescents affected by perinatal HIV. Future studies may consider these findings to develop tailored nutritional interventions.

OBJECTIVE:To (1) determine how serum fatty acid (FA) levels differ by developmental stage, (2) quantify associations between perinatal HIV-related factors and PUFA levels and (3) examine the heterogeneity of these associations by developmental stage. DESIGN:Cross-sectional secondary analysis of baseline data from two prospective cohorts. SETTING:Kampala, Uganda. PARTICIPANTS:243 children (6-10 years old) and 383 adolescents (11-18 years old) were recruited at Kawaala Health Center based on perinatal HIV status. Youth (children and adolescents) were classified as: those with perinatal HIV infection (PHIV: n 212), those perinatally HIV exposed but remained uninfected (HEU: n 211) and those perinatally HIV unexposed and uninfected (HUU: n 203). RESULTS:Adolescents had lower n-6 and n-3 PUFA levels than children, and among adolescents, these levels increased with age. Relative to children HUU, children PHIV had a higher triene:tetraene ratio and 20:3n-9 (indicators of essential fatty acid deficiency (EFAD)). Adolescents PHIV v. HUU had lower 20:5n-3 levels. When considering in utero/peripartum antiretroviral therapy (IPA) exposure, the FA profile was indicative of EFAD for youth PHIV with (a) no IPA exposure and (b) combination IPA exposure, whereas non-nucleoside RT inhibitor+nucleoside RT inhibitor exposure was associated with a favourable FA profile among youth PHIV and HEU (all P < 0·05). CONCLUSION:In this sample, perinatal HIV status was associated with low PUFA levels, and these associations varied by developmental stage and IPA exposure type. Future research should elucidate the contribution of IPA exposure type to EFAD and the implications of these differences on growth and cognitive development.

BACKGROUND:Adolescence is critical for executive function development, and fatty acids, vital for brain development, may influence this process. This influence is understudied in populations affected by HIV, where malnutrition and neuroinflammation persist. OBJECTIVES:This study aimed to determine associations between serum fatty acid concentrations and executive function in Ugandan adolescents over 12 mo and evaluate modification by perinatal HIV status. It was hypothesized that PUFA concentrations were associated with improved executive function, whereas SFA concentrations were associated with worse executive function, especially in adolescents affected by perinatal HIV exposure/infection. METHODS:Adolescents with perinatal HIV infection (APHIV; n = 122), adolescents perinatally exposed to but uninfected with HIV (AHEU; n = 130), and adolescents perinatally unexposed to and uninfected with HIV (AHUU; n = 123) were analyzed. Serum fatty acid concentrations were measured at baseline. Questionnaire- and performance-based measures of executive function (analyzed as z-scores) were assessed at baseline and 6 and 12 mo. Linear mixed-effects models were used to analyze associations between baseline serum fatty acid tertiles and repeated executive function measures. Mean differences (MDs) and their 95% CIs are reported. RESULTS:Among all adolescents, moderate compared with low ω-3 PUFA levels were associated with decreases in self-report executive dysfunction (total ω-3 PUFA-MD: -0.51; 95% CI: - 0.87, -0.15; Omega-3 Index-MD: -0.52; 95% CI: -0.88, -0.16; highly unsaturated fatty acid ratio-MD: -0.42; 95% CI: -0.79, -0.06; DHA-MD: -0.58; 95% CI: -0.94, -0.21). Among APHIV, high EPA (MD: 1.07; 95% CI: 0.27, 1.87) and select SFA concentrations (arachidic acid-MD: 0.86; 95% CI: 0.38, 1.34; behenic acid-MD: 0.76; 95% CI: 0.23, 1.29; lignoceric acid-MD: 0.78; 95% CI: 0.24, 1.31) correlated with increased self-report and performance-based executive dysfunction, respectively. CONCLUSIONS:Overall, higher ω-3 PUFA concentrations are associated with better questionnaire-based executive function, but high EPA and SFA concentrations are associated with worse executive function among APHIV. These findings support the potential of ω-3 PUFAs to improve executive function in vulnerable populations and highlight the importance of further studying the relationship between fatty acids and executive function among APHIV.

ABSTRACTIn the combined antiretroviral therapy era, limited information exists about cognitive function in children exposed perinatally to human immunodeficiency virus (HIV). To address this, we evaluated executive function (EF) among groups with known HIV exposure status during the perinatal period and at ages 6-10 years: children HIV-infected perinatally (CPHIV, n = 99), children born to HIV-infected mothers, but were HIV negative at enrollment (CPHEU, n = 97), and HIV unexposed, uninfected community controls (CHUU, n = 98). Caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF) to assess two dimensions of child EF (BRI: Behavioral Regulation Index; MCI: Metacognition Index) and a combination of these dimensions (General Executive Composite). We derived Z-scores for BRIEF measures using the CHUU group as the reference and used generalized linear models to estimate mean differences among the groups. The CPHIV and CPHEU groups did not differ from the CHUU group on the GEC or MCI. However, the CPHIV group scored lower than CHUU on the BRI, which is indicative of better functioning in this domain (β = -0.40, 95% CI -0.77, -0.03). Results were unaffected following adjustment. EF scores did not differ substantially across perinatal HIV exposure groups, though we observed evidence that CPHIV may thrive in the BRI domain.

Mental health outcomes are substantially poorer among people with HIV than the general population. In a sample of 862 children and 439 adult caregivers in Kampala, Uganda, we investigated whether the trajectories of depressive symptoms over 24 months may be influenced by participants’ HIV status and baseline inflammation (indexed via high-sensitivity C-reactive protein, CRP). At higher baseline CRP concentrations, children with HIV showed lower baseline depressive symptoms relative to children without HIV. Over time, depressive symptoms increased in children with HIV but decreased in children without HIV. No differences in trajectories were observed in adults. Our results suggest that given high baseline inflammation, recovery from depressive symptoms may be significantly slower among children living with HIV compared to those without HIV. Specific interventions to reduce inflammation may need to be combined with more regular, holistic, and personalised interventions to alleviate depressive symptoms among children with HIV.

Survival is possible for children perinatally exposed to or infected by HIV in the post-combined antiretroviral therapy era and identifying factors affecting children's ability to thrive has public health significance. Caregiver mental health is one such factor to consider given its impact on child development, but previous work has not included a full complement of HIV exposure/infection groups within HIV-endemic settings. We compared depressive symptoms among caregivers of 3 groups of 6-10-year-olds in Uganda: children with perinatally acquired HIV infection (CPHIV, n = 102), children with perinatal HIV exposure, but no infection (CPHEU, n = 101), and children without perinatal HIV exposure or infection (CHUU, n = 103). The Hopkins Symptom Checklist was used to assess caregiver depressive symptoms. Generalized linear models were used to estimate group mean differences. Adjusted models included caregiver demographics, social support, and lifetime trauma. Depression symptoms were higher among CPHEU compared to CPHIV caregivers (model coefficient [B] = -3.5, 95%CI -5.3, -1.8). This finding was minimally attenuated following adjustment for covariates (B = -2.2, 95%CI -4.1, -0.4) and among biological mothers. At lower levels of social support and wealth, CPHEU caregivers reported higher levels of depression symptoms than CPHIV caregivers. Our findings point to unmet mental health needs among CPHEU caregivers.

Objectives: To determine if fatty acid (FA) levels differ by adolescent status and quantify the relationship between polyunsaturated fatty acid (PUFA) levels and perinatal HIV-related factors among Ugandan children and adolescents. Methods: 243 school-aged children (6-10 years old) and 383 adolescents (11-18 years old) were recruited in Kampala. Baseline serum samples were obtained and methylated to quantify FAs using gas-chromatography mass-spectroscopy. Perinatal HIV infection/exposure and IPA exposure status were established from medical records. Descriptive statistics were used to analyze differences in FA levels by adolescent status, and multivariable linear regression analyses were performed to relate risk factors to select PUFA levels in each youth group. Results: Adolescents had higher saturated FA (55.3% v. 43.4%) and monounsaturated FA (21.2% v. 7.2%) and lower n-6 (20.8% v. 46.4%) and n-3 (2.5% v. 2.9%) PUFA levels than children (all p < 0.05). Relative to children HIV unexposed uninfected (HUU), children with perinatal HIV infection (PHIV) had unfavorable FA levels (higher T:T ratio and Mead acid) with variations by IPA exposure type. Specifically, FA profile was worse for children PHIV with no IPA and combination ART (cART) exposure, but nevirapine+zidovudine+lamivudine (NVP+ZDV+3TC) exposure was associated with a favorable FA profile among children PHIV and children HIV exposed uninfected (HEU). Among adolescents, increasing age was associated with a more favorable FA profile. Overall, relative to adolescents HUU, adolescents PHIV had lower EPA levels, but FA levels varied further by IPA exposure type. Specifically, adolescents PHIV with no IPA exposure had lower linoleic acid and EPA levels and those with cART exposure had lower n-3 PUFA levels, but adolescent PHIV exposed to NVP±ZDV had more beneficial FA levels (all p < 0.05). Conclusions: Adolescents are more vulnerable to low PUFA levels than children, but their levels increase with age. Overall, PHIV and HEU status are associated with low levels for some n-3 and n-6 PUFAs. However, the relationship between perinatal HIV status and FA levels varies by adolescent status and IPA exposure type. Additional studies examining the contributory role of IPA exposure type are warranted. Funding Sources: National Institute of Neurological Disorders and Stroke of the National Institutes of Health.

In utero/peripartum antiretroviral (IPA) drug exposure in human immunodeficiency virus (HIV)-exposed children has established benefit for prevention of HIV mother-to-child-transmission but its association with height-for-age by adolescence is unknown. Hence we quantify IPA-associated growth differences at 6 to 18 years old among children with perinatally acquired HIV (CPHIV) infection and children HIV exposed but uninfected (CHEU) relative to children HIV unexposed and uninfected (CHUU). Cohort study. Kampala, Uganda. Two hundred thirty eight community controls and 490 children of women living with HIV born between 2000 and 2011 in a community were enrolled at 6 to 18 years of age and followed every 6 months for 1 year. Height-for-age determined at enrollment, 6 and 12 months after enrollment using the World Health Organization reference. IPA exposure was retrospectively determined from medical records and categorized as: no IPA, single-dose nevirapine with/without zidovudine (sdNVP ± AZT), sdNVP + AZT + lamivudine, or combination antiretroviral therapy (cART). Mean differences (β) with 95% confidence intervals (CIs) in height-for-age over 12 months were evaluated according to IPA exposure for CPHIV and CHEU and relative to CHUU using longitudinal linear mixed effects models adjusted for caregiver factors (sex, age, education, functioning in caregiving role, and lifetime adversity) in Statistical Analysis Software (v.9.4). Regardless of IPA type, CPHIV grew worse than CHUU by school-age/adolescence (β = -0.30, 95% CI: -0.48, -0.11). Relative to CHUU height-for-age was similar for CHEU exposed to sdNVP ± AZT (β = -0.16, 95% CI: -0.46, 0.14) and for CHEU exposed to sdNVP + AZT + lamivudine (β = 0.08, 95% CI: -0.20, 0.35). However, CHEU without any IPA exposure had lower height-for-age (β = -0.27, 95% CI: -0.52, -0.00) whereas CHEU with cART exposure had greater height-for-age (β = 0.41, 95% CI: 0.10, 0.71) in comparison with CHUU by 6 to 18 years old. Our findings suggest that CHEU may achieve height-for-age parity with CHUU by school-age and adolescent years- especially if provided benefit of effective cART in the peripartum period. However, CPHIV regardless of IPA exposure type and CHEU without IPA exposure remain at a disadvantage and will benefit from intervention to support their growth.

Malnutrition is prevalent in low-middle-income countries (LMICs), but it is usually clinically diagnosed through abnormal anthropometric parameters characteristic of protein energy malnutrition (PEM). In doing so, other contributors or byproducts of malnutrition, notably essential fatty acid deficiency (EFAD), are overlooked. Previous research performed mainly in high-income countries (HICs) shows that deficiencies in essential fatty acids (EFAs) and their n-3 and n-6 polyunsaturated fatty acid (PUFA) byproducts (also known as highly unsaturated fatty acids or HUFAs) lead to both abnormal linear growth and impaired cognitive development. These adverse developmental outcomes remain an important public health issue in LMICs. To identify EFAD before severe malnutrition develops, clinicians should perform blood fatty acid panels to measure levels of fatty acids associated with EFAD, notably Mead acid and HUFAs. This review demonstrates the importance of measuring endogenous fatty acid levels for measuring fatty acid intake in various child populations in LMICs. Featured topics include a comparison of fatty acid levels between global child populations, the relationships between growth and cognition and PUFAs and the possible mechanisms driving these relationships, and the potential importance of EFAD and HUFA scores as biomarkers of overall health and normal development.

In utero/peripartum antiretroviral therapy (IPA) exposure type was examined in relationship to mental health symptoms among 577 children with perinatally acquired HIV (CPHIV), children perinatally HIV exposed but uninfected (CHEU), and children HIV unexposed uninfected (CHUU). IPA exposure was categorized for CPHIV and CHEU as none, single-dose nevirapine with or without zidovudine (sdNVP±AZT), sdNVP+AZT+lamivudine (3TC), or combination antiretroviral therapy (cART). Anxiety and depressive symptoms were reported at baseline, 6-, and 12-month follow-up per behavioral assessment system for children. Multivariable linear mixed models were used to estimate differences (b) with 95% confidence intervals (95% CI) for IPA exposure types versus CHEU without IPA exposure. Depressive and anxiety symptoms were lower in CHUU relative to CHEU and CPHIV but did not differ between CPHIV and CHEU. CHEU with sdNVP±AZT exposure had greater anxiety (b = 0.51, 95% CI: [0.06, 0.96]) and depressive symptoms (b = 0.48, 95% CI: [0.07, 0.89]) than CHEU without IPA exposure. CHEU with sdNVP+AZT+3TC exposure had higher anxiety (b = 0.0.45, 95% CI: [0.03, 0.86]) and depressive symptoms (b = 0.72, 95% CI: [0.27, 1.17]) versus CHEU without IPA exposure. Depressive and anxiety symptoms were not different for CHEU and CPHIV exposed to cART (b = 0.12-0.60, 95% CI: [-0.41, 1.30]) and CHEU and CHUU (b = -0.04 to 0.08, 95% CI: [-0.24, 0.29]) without IPA exposure. Among CHEU, peripartum sdNVP±AZT and sdNVP+AZT+3TC but not cART compared to no IPA exposure was associated with clinically important elevations in anxiety and depressive symptoms. Monitoring of mental health trajectory of HIV-affected children considering IPA is needed to inform mental health interventions. Patient Contribution: Caregivers and their dependents provided consent for participation and collaborated with study team to identify mutually convenient times for protocol implementation.

Abstract Resilience-promoting factors (RPF), minority race and their interaction, were evaluated as determinants of quality of life (QOL) decline in a nationally representative sample of US adults ≥50 years old (N=3932) with heart disease and/or type-2 diabetes from 2006-2014 as part of the Health and Retirement Study. RPF included personal mastery and positive social support (PSS). QOL was assessed by self-rated health (SRH) and defined as poor (fair/poor), good, or excellent (very good/ excellent). Repeated measures multinomial regression using generalized estimating equations (GEEs) related RPF, race, and their interaction to SRH declines over 8 years. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with adjustment for time, sociodemographic and behavioral confounders. Low mastery, low PSS and minority race were each associated with higher odds of QOL declines over 8 years (mastery OR- 2.27, 95% CI: 1.83- 2.81; PSS OR- 1.35, 95% CI: 1.10-1.65; African American OR- 1.46, 95% CI: 1.25-1.70, and Other race OR- 1.43, 95% CI: 1.10-1.86). QOL declines related to PSS-friends varied by race and time (race x time x PSS-friends, p=0.093). Among older Caucasians, the association between PSS and QOL declines did not vary over time (p=0.676). However, among African Americans and Other race, low PSS was associated with increased odds of QOL declines over time (p=0.031 and p=0.034 respectively). RPF and minority race predicted QOL decline in older Americans with comorbid conditions. Policies/ interventions to enhance resiliency represent a viable strategy for mitigating racial disparities in overall wellbeing and improving health outcomes in aging Americans.

We tested the hypothesis that vitamin D deficiency (VDD) is associated with higher developmental disorder probability in 604 children with perinatal HIV infection (CPHIV, n = 199), HIV exposed and uninfected (CHEU, n = 196), and HIV unexposed uninfected (CHUU, n = 201). Children at 6–18 years old and their adult caregivers were assessed at enrollment, 6, and 12-month follow-ups. Serum 25-hydroxyvitamin-D (25OHD) levels in children quantified per the NHANES protocol were used to define VD categories as VDD (25OHD < 20 ng/mL), VD insufficient (VDI, 20 ≤ 25OHD ≤ 25 ng/mL), and VD sufficient (VDS = reference group if 25OHD > 25 ng/mL). Perinatal HIV status per DNA polymerase chain reaction/HIV rapid diagnostic tests included: CPHIV, CHEU, and CHUU. Developmental stage was defined as pre-adolescent (age < 11) vs. adolescent (age ≥ 11) years. Caregiver responses to standardized questions from Behavioral Assessment System for Children, Third Edition (BASC-3), were used to calculate probability scores for four disorders, namely: autism (ASD), attention deficit & hyperactivity (ADHD), emotional behavioral disorder (EBD), functional impairment (FI), and resiliency at 0, 6 and 12 months. Multivariable longitudinal models estimated VD-associated standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) in respective probability scores in Statistical Analysis Software (v.9.4). Baseline VDD vs. VDS predicted higher probability scores of moderate clinical importance for ASD, ADHD, EBD, and higher FI among pre-adolescents (SMD = 0.32 to 0.40, 95% CI: 0.00 to 0.74). VDD was not associated with resiliency or any developmental disorders among adolescents. VDD predicted higher developmental disorder and FI scores over 12 months in a developmental stage-dependent manner. This relationship requires further understanding to appropriately target future interventions.

Children in Uganda are at risk for significant cognitive sequelae from severe malaria. Computerized cognitive rehabilitation training (CCRT) represents a potential method to improve working memory, behavior, and executive functioning, cognitive domains most at risk following severe malaria. The primary aim of this study was to complete a secondary analysis of data from a concluded CCRT randomized control trial in order to compare the training efficiency of a commonly used CCRT program under conditions of titrated (adaptive) or non-titrated (non-adaptive) training and with children with increasing malaria severity to determine how various factors may affect potential CCRT improvement. A total of 201 school-aged children (66.2% boys) who were either healthy (n = 102) or previously diagnosed with severe or cerebral malaria (n = 99) were randomized into two active treatment arms (titrated and non-titrated learning). Each child received 24 one-hour sessions of training over 8 weeks using Captain's Log (R) CCRT by BrainTrain, which includes a comprehensive set of CCRT tasks. Children generally benefited from CCRT over the 24 training sessions, but titrated CCRT showed a clear advantage over non-titrated. Severity of illness or factors such as BMI, did not moderate CCRT performance indicators. These findings support our hypothesis that titrated CCRT would result in steeper improvement in learning, but do not support our hypothesis that history of recent significant illness would affect learning proficiency. Findings were evident across all CCRT performance scores, even given that children were from generally rural, low-resource settings and were generally unfamiliar with computers.

(1) We examined the hypothesis that in utero/peripartum antiretroviral (IPA) exposure may affect the likelihood of developmental disorders—i.e., attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and functional impairment (FI). (2) Children and their primary caregivers were enrolled and followed for 12 months. The sample included 250 children perinatally HIV-infected (CPHIV), 250 children HIV-exposed and uninfected (CHEU) of women living with HIV, and 250 children HIV unexposed and uninfected (CHUU) at 6–18 years of age. CHEU’s IPA exposure -type was established via medical records and categorized as no IPA, single-dose nevirapine with/without zidovudine (SdNVP ± AZT), SdNVP + AZT + Lamivudine (3TC), or combination ART (cART). Developmental disorders were assessed at months 0, 6, and 12 per caregiver response to standardized questions from the third edition of Behavioral Assessment System for Children. Multivariable repeated measures linear regression models estimated standardized mean differences (SMDs) with 95% confidence intervals (95% CI) according to the IPA exposure type relative to CHUU with adjustment for the dyad’s sociodemographic and psychosocial factors. (3) Relative to the CHUU, outcomes were similar for CPHIV/CHEU with cART, SdNVP ± AZT, and no anti-retroviral drug exposure in the peripartum period. For CHEU relative to CHUU, SdNVP + AZT + 3TC exposure was associated with lower resiliency (SMD = −0.26, 95% CI: −0.49, −0.51), and elevated scores on ADHD (SMD = 0.41, 95% CI: 0.12, 0.70), ASD (SMD = 0.40, 95% CI: 0.19, 0.61), and EBD (SMD = 0.32, 95% CI: 0.08, 0.56) probability and functional impairment (SMD = 0.39, 95% CI: 0.18, 0.61) index scores. With the exception of ADHD, the adverse association between SdNVP + AZT + 3TC and outcomes were replicated for CPHIV vs. CHUU. (4) The results provided reassuring evidence that cART exposure in the peripartum period is unlikely to be adversely associated with developmental disorder probability scores in late childhood and adolescent years. However, the peripartum SdNVP + AZT + 3TC exposure associated elevation in developmental disorder probability and functional limitation at 6–18 years of life is a concern.

Toxic stress (TS), resiliency-promoting factors (RPFs) and their interactions were investigated in relationship to incident dementia in a sample (n = 6516) of US adults ≥50 years old enrolled in the HRS between 2006-2016. TS included experiences of everyday discrimination and RPF included personal mastery. Race/ethnicity was self-reported as African American (AA), Caucasian, or Other. Multivariable Cox proportional hazards regression models estimated TS-, RPF- and race-associated hazard ratios (HR) for dementia diagnosis and 95% confidence intervals (CIs) with adjustment for comorbidity and socio-demographic factors. Discrimination-associated risk of dementia diagnosis on average increased with education level [discrimination x education, p = 0.032; HR = 1.75 (95% CI: 1.01–3.03) if < high school, HR = 5.67 (95% CI: 2.94–10.94) if high school completed and HR = 2.48 (95% CI: 1.53–4.00) if ≥some college education]. Likewise, AA vs. Caucasian race disparity in new-onset dementia was evident (HR = 2.12, 95% CI: 1.42–3.17) among adults with high-mastery while absent (HR = 1.35, 95% CI: 0.75–2.41) among adults with low mastery (Mastery x Race, p = 0.01). TS is a contextual driver of incident dementia that seemingly operates in a race and RPF-dependent manner. Heterogeneity pattern suggests that TS may overwhelm the cognitive reserve benefit of RPF particularly in status-inconsistent contexts including persons subjected to discrimination despite high education and in AA individuals despite high mastery. Policies that reduce discrimination and promote equitable treatment by race/ethnicity may support cognitive resiliency and reduce the risk of dementia diagnosis in adult Americans.