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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.

Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

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.

Objectives: HIV-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction in HIV-infected children (with and without hyperlipidaemia) with those in HIV-exposed, uninfected (HEU) children enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers., Methods: A prospective cohort study was carried out. Biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP1)], coagulant dysfunction (fibrinogen and P-selectin), endothelial dysfunction [soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM) and E-selectin], and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded., Results: The median ages of the children were 12.3 years in the HIV-infected group and 10.1 years in the HEU group. Body mass index (BMI) z-scores, waist and hip circumferences, and percentage body fat were lower in the HIV-infected children. Total and non-high-density lipoprotein (HDL) cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children also had higher MCP-1, fibrinogen, sICAM and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavourable lipid profiles were positively associated with IL-6, MCP-1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP-1 and CRP) and endothelial dysfunction (sICAM and sVCAM)., Conclusions: HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavourable lipid levels and active HIV replication., (© 2011 British HIV Association.)

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.

Objective: Antiretroviral (ARV) drugs are routinely provided to HIV-infected pregnant women to prevent HIV mother-to-child transmission. Although ARV use has significantly reduced mother-to-child transmission to <2% in the United States, it remains crucial to monitor uninfected infants and children for adverse consequences of in utero ARV exposure., Methods: We studied neurodevelopmental function in HIV-exposed uninfected children who were enrolled in Pediatric AIDS Clinical Trials Group 219/219C, a multisite, prospective, cohort study. Mental and motor functioning were assessed with the Bayley Scales of Infant Development (BSID), first and second editions. ARV exposure information was collected during pregnancy or within the first years of life. Linear regression methods were used to evaluate the association of in utero ARV exposure on Mental Developmental Index and Psychomotor Developmental Index at 2 years of age, controlling for demographic factors (age, gender, and race/ethnicity) and potential confounders: test version, primary language, primary caregiver, caregiver education level, low birth weight, geographic and urban/rural location, birth year, and maternal illicit drug use., Results: Among 1840 infants who were born between 1993 and 2006, 1694 (92%) were exposed to ARV in utero and 146 (8%) were not exposed. After controlling for confounders, children who were exposed in utero to any ARV did not have lower Mental Developmental Index and Psychomotor Developmental Index scores than unexposed children. Among low birth weight infants, significantly higher BSID scores were observed for prenatally ARV-exposed than unexposed children. Maternal illicit drug use was reported for 17% of mothers but was not associated with BSID scores., Conclusions: Mental and motor functioning scores were not lower for infants with in utero ARV exposure compared with no exposure. Although these results are reassuring, continued evaluation of uninfected children with in utero ARV exposure for long-term adverse outcomes is important.