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BACKGROUND Depression is frequent among youth living with HIV (YLWH). Studies suggest that manualized treatment guided by symptom measurement is more efficacious than usual care. SETTING This study evaluated manualized, measurement-guided depression treatment among YLWH, aged 12-24 years at 13 US sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Network. METHODS Using restricted randomization, sites were assigned to either a 24-week, combination cognitive behavioral therapy and medication management algorithm (COMB-R) tailored for YLWH or to enhanced standard of care, which provided standard psychotherapy and medication management. Eligibility included diagnosis of nonpsychotic depression and current depressive symptoms. Arm comparisons used t tests on site-level means. RESULTS Thirteen sites enrolled 156 YLWH, with a median of 13 participants per site (range 2-16). At baseline, there were no significant differences between arms on demographic factors, severity of depression, or HIV status. The average site-level participant characteristics were as follows: mean age of 21 years, 45% male, 61% Black, and 53% acquired HIV through perinatal transmission. At week 24, youth at COMB-R sites, compared with enhanced standard of care sites, reported significantly fewer depressive symptoms on the Quick Inventory for Depression Symptomatology Self-Report (QIDS-SR score 6.7 vs. 10.6, P = 0.01) and a greater proportion in remission (QIDS-SR score ≤ 5; 47.9% vs. 17.0%, P = 0.01). The site mean HIV viral load and CD4 T-cell level were not significantly different between arms at week 24. CONCLUSIONS A manualized, measurement-guided psychotherapy and medication management algorithm tailored for YLWH significantly reduced depressive symptoms compared with standard care at HIV clinics.

Depressive symptoms among HIV-positive (HIV+) women may negatively impact their health and possibly that of their young children through risk of compromised caregiving. We evaluated how depression symptoms in predominantly (97%) female caregivers relate to neurodevelopmental outcomes in their HIV affected children. Data come from the IMPAACT P1104s Study, an observational cohort across six sites in four countries: Zimbabwe, South Africa, Uganda and Malawi. Participants (n=611) were 5-11 year old children with HIV (HIV), HIV exposed uninfected (HEU), or HIV unexposed uninfected (HUU). Primary caregivers were assessed for depression with the Hopkins Symptom Checklist (HSCL) and children with Behavior Rating Inventory for Executive Function (BRIEF) parent-report, Kauffman Assessment Battery for Children II (KABC), Bruininks-Oseretsky Test of Motor Proficiency 2(nd) Ed. (BOT-2), Test of Variables of Attention (TOVA), Multiple Indicators Cluster Survey, Child Disability and Development scales (MICS-4). Caregivers with higher depression scores (> 1.75 mean HSCL score) reported more executive function problems in their children, regardless of HIV status. All executive function scores were significantly (p

Antiretroviral (ARV) adherence is critical in monitoring disease response in youth with perinatally-acquired HIV (PHIV). We used pharmacy refill (PR) information for PHIV youth from the PHACS Memory Sub-study to calculate medication availability over 2, 4, and 6 months. PR, a proxy of adherence, was compared with self-reported 7-day adherence in predicting suppressed viral load (SVL

Prospective memory (PM), “remembering to remember,” has been linked to important functional outcomes in adults. Studies of PM in children and adolescents would benefit from the development and validation of developmentally appropriate clinical measures with known psychometric properties. The Prospective Memory Assessment for Children & Youth (PROMACY), a performance-based measure of PM, was developed for the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, Memory and Executive Functioning Substudy, and includes Summary, Time-, and Event-based scores derived from eight trials with an ongoing word search task. Fifty-four healthy perinatally HIV-exposed, uninfected children and youth, mean age 13 years, 54% female, 76% Black/non-Hispanic, and 61% impoverished were included in this psychometric analysis. PROMACY Summary Scores demonstrated low, but broadly acceptable internal consistency as measured by Cronbach’s alpha and Spearman-Brown. Better PROMACY performance was associated with older age, but no other demographic factors. Generally medium-sized correlations were observed between the PROMACY Summary Score and standard clinical measures of retrospective memory, working memory, executive functions, and IQ. Findings from this preliminary psychometric study of non-clinical children and youth provide cautious support for the internal consistency and construct validity of PROMACY’s Summary Score that awaits replication and extension in larger samples of healthy children, youth and clinical populations.

Youth with perinatal HIV infection (PHIV) are at increased risk for neurocognitive impairment. 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 non-adherence. 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 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 neurocognitive impairment (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

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.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.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, P0.001), adjusting for demographic variables (age, race and caregiver education).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.

BACKGROUND Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. METHODS In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. FINDINGS At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

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

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

Brief psychiatric assessment tools are needed for evaluating children affected by HIV for emotional and behavioral problems. We compared a self-administered symptom rating scale (CASI-4R) to a semi-structured diagnostic interview (DICA-P) in 136 U.S. children affected by HIV. Agreement and performance measures for the two instruments were computed for attention deficit hyperactivity disorder, depression, anxiety, and disruptive behavior. Correlations and regression analyses were conducted to compare the two instruments, and to evaluate their associations with social, academic, and global function. Higher CASI-4R symptom severity scores were associated with DICA diagnoses (p

Children with HIV infection (HIV+) are at neuropsychological risk, but few studies have evaluated this at multiple sites in low-income and middle-income countries. We compared neuropsychological outcomes at enrollment (5 years age) among HIV+, HIV perinatally exposed uninfected (HEU), and HIV unexposed uninfected (HUU) children from four sub-Saharan countries.IMPAACT P1060 compared nevirapine versus lopinavir/ritonavir-based antiretroviral treatment (ART) in HIV-infected children 6-35 months of age. The present study (P1104s) enrolled P1060 children at 5-11 years of age and evaluated their neuropsychological performance over 2 years using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), Tests of Variables of Attention (TOVA), Bruininks-Oseretsky Test, 2nd edition (BOT-2), and parent-reported Behavior Rating Inventory of Executive Function (BRIEF). Cohorts were compared using generalized estimating equations least-squares means adjusted for site, child age and sex, and personal and social characteristics for child and caregiver.Six hundred and eleven (246 HIV+, 183 HEU, 182 HUU) of the 615 enrolled at six sites [South Africa (three), Zimbabwe, Malawi, Uganda] were available for analysis. Mean age was 7.2 years, 48% male, 69% in school. Unadjusted and adjusted comparisons were consistent. HIV+ children performed significantly worse than HEU and HUU cohorts on all KABC-II cognitive performance domains and on BOT-2 total motor proficiency (P 0.001), but not on the BRIEF Global Executive Indices. HUU and HEU cohorts were comparable on cognitive outcomes. HIV+ children initiated on ART before 1 year of age had significantly better BRIEF evaluations (lower scores - fewer behavior problems), compared with those started after (P = 0.03).Significant cognitive deficits were documented among HIV+ children at school age, even when started on ART at an early age. Earlier HIV treatment, neuropsychological monitoring, and rehabilitative interventions are all needed. Subsequent testing for 2 more years will help further evaluate how HIV infection and exposure affect the developmental trajectory.

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

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.

Little is known about the relationship between traumatic head injury (THI) and psychiatric morbidity in torture survivors. We examine the relationship between THI and depression, PTSD, post-concussive syndrome (PCS), disability and poor health status in Vietnamese ex-political detainees who survived incarceration in Vietnamese re-education camps. A community sample of ex-political detainees (n = 337) and a non-THI, non-ex-detainee comparison group (n = 82) were surveyed. Seventy-eight percent of the ex-political detainees had experienced THI; 90.6% of the ex-political detainees and 3.6% of the comparison group had experienced 7 or more trauma events. Depression and PTSD were greater in ex-detainees than in the comparison group (40.9% vs 23.2% and 13.4% vs 0%). Dose–effect relationships for THI and trauma/torture in the ex-political detainee group were significant. Logistic regression in the pooled sample of ex-detainees and the comparison group confirmed the independent impact of THI from trauma/torture on psychiatric morbidity (OR for PTSD = 22.4; 95% CI: 3.0–165.8). These results demonstrate important effects of THI on depression and PTSD in Vietnamese ex-detainees who have survived torture.

Learning and memory in youth with perinatally acquired HIV (PHIV) are poorly understood, despite their importance for academic, healthcare and daily functioning.PHIV (n = 173) and perinatally HIV-exposed but uninfected (PHEU, n = 85) participants (aged 9-19 years) in a substudy of the Pediatric HIV/AIDS Cohort Study completed age-standardized tests of verbal and visual learning and delayed memory. Linear regression models implemented via generalized estimating equations were used to compare memory measures in PHEU participants versus PHIV youth with and without Centers for Disease Control and Prevention class C diagnosis (PHIV-C, n = 45 and PHIV-non-C, n = 128, respectively), adjusting for sociodemographic covariates.Participants (mean age = 14.10 years) were 54% female, 75% Black and 18% Hispanic. Although unadjusted analyses showed significantly lower visual recognition memory and verbal delayed recall for PHIV-C compared with PHEU participants and lower verbal learning for PHIV-C and non-C groups compared with PHEU, differences persisted only for visual recognition memory after adjusting for sociodemographic covariates. For PHIV youth, current CD4%25 was associated with poorer verbal learning, and older age at peak viral load was associated with poorer verbal delayed recall and design memory.Youth with PHIV, particularly those with Centers for Disease Control and Prevention class C diagnosis, showed poorer performance on some measures of learning and memory compared with PHEU. Although group differences in verbal memory were largely attributable to sociodemographic characteristics, associations of class C diagnosis with poorer visual recognition memory and of current CD4% with poorer verbal learning suggest subtle effects of HIV on learning and memory in youth with PHIV.

This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection.Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria.Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD.A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.

Based on studies conducted throughout the world, it is now well established that youth with perinatal HIV infection (PHIV) experience relatively high rates of psychopathology.1–5 This is not unexpected as psychiatric symptoms in adults are not only implicated in HIV disease transmission6 but also associated with less than optimal strategies for managing child behavior7 and evidence moderate to high heritability.8,9 There is also fairly compelling evidence indicating HIV contributes to neurocognitive impairment,10–13 and treatment with antiretroviral drugs is onerous14 and may result in a range of annoying somatic symptoms.15,16 Thus, over and above the challenges of coping with a chronic illness17 associated with considerable negative social stigma, youth with PHIV are vulnerable to a number of biological and environmental risk factors.18–20 In addition to the obvious need to provide adequate care, the mental health concerns of youth with HIV have additional implications for clinicians. For example, psychiatric symptoms are associated with risky sexual behaviors and disease transmission,1,18,19,21–24 substance use,19,25,6 poor adherence to pharmacotherapy,27–31 and HIV illness parameters,13 but relations among these variables are complex and may vary as a function of study population characteristics.32 What is much less clear is the role of HIV infection or its attendant therapies in either contributing to or exacerbating emotional and behavioral problems. There are a handful of studies with appropriate comparison samples that have examined this topic, most of which have used cross-sectional designs. For example, Mellins et al33 found 3- to 8-year-old children with PHIV did not differ in the severity of caregiver ratings of emotional behavioral problems from HIV-exposed but uninfected peers. However, in a later study Mellins et al34 also examined rates of psychiatric disorders in the past year in older youth (aged 9–16 years) with HIV versus controls recruited from 4 medical centers. Here, they found a significantly higher overall rate of psychiatric disorders assessed with a structured interview in youth with PHIV (61%) versus exposed but uninfected peers (49%); however, group differences were not significant for specific disorders with the exception of attention-deficit hyperactivity disorder (ADHD) (18 and 8%, respectively). Recently, we reported on 319 youth with PHIV and 256 peers who were HIV-exposed or living in house-holds with at least 1 HIV-infected family member (peer comparisons). Participants were recruited from 29 sites in the United States and Puerto Rico.35 Youth with PHIV were relatively healthy, and almost all youth were currently receiving antiretroviral therapy. Many youth with PHIV (27%) and peer comparisons (26%) were rated (either self- or caregiver report) as having psychiatric problems that interfered with academic or social functioning, and the percentage of youth in both groups with the symptoms of specific disorders was clearly higher than the general population. Moreover, youth with PHIV had higher lifetime rates of special education (44%/32%) and interventions for emotional or behavioral problems (37%/22%) than uninfected peers, suggesting that lifetime rates of mental health concerns may actually be higher in youth with PHIV. In a related report about the same sample,36 we found several HIV illness parameters including lower nadir and entry CD4% associated with psychiatric illness, particularly conduct disorder (CD), as well as poorer quality of life and social and academic performance, suggesting that either the virus or severe immune suppression may have an effect on these functions. Collectively, the findings of these controlled, primarily cross-sectional studies support earlier reports of mental health concerns in youth with PHIV and identify several potential risk factors; however, they generally do not address the incidence of psychiatric conditions or changes in symptom or treatment status over time, relative to an appropriate comparison group, all of which help illustrate the scope of clinical management concerns. This study expands on our prior research by characterizing (a) the incidence of emerging psychiatric symptoms in youth with PHIV and peer comparisons during a 2-year time interval, (b) predictors of emerging symptoms (demographic, psychosocial, and HIV illness variables), and (c) rates of pharmacotherapy for emerging symptoms in these 2 groups of youth. This is one of the first published studies to address these topics using a controlled, prospective, longitudinal design with a relatively large, geographically representative sample of youth with PHIV, most of whom were treated with highly active antiretroviral therapy (HAART).

Mitochondrial dysfunction has been associated with both human immunodeficiency virus (HIV) infection and exposure to antiretroviral therapy. Mitochondrial dysfunction has not been widely studied in HIV-infected children. We estimated the incidence of clinically defined mitochondrial dysfunction among children with perinatal HIV infection.Children with perinatal HIV infection enrolled in a prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993 through 2004 were included. Two clinical case definitions of mitochondrial dysfunction, the Enquête Périnatale Française criteria and the Mitochondrial Disease Classification criteria, were used to classify signs and symptoms that were consistent with possible mitochondrial dysfunction. Adjusted odds ratios of the associations between single and dual nucleoside reverse-transcriptase inhibitor use and possible mitochondrial dysfunction were estimated using logistic regression.Overall, 982 (33.5%) of 2931 children met 1 or both case definitions of possible mitochondrial dysfunction. Mortality was highest among the 96 children who met both case definitions (20%). After adjusting for confounders, there was a higher risk of possible mitochondrial dysfunction among children who received stavudine regardless of exposure to other medications (odds ratio, 3.44 [95% confidence interval, 1.91-6.20]) or who received stavudine-didanosine combination therapy (odds ratio, 2.23 [95% confidence interval, 1.19-4.21]). Exposure to lamivudine and to lamivudine-stavudine were also associated with an increased risk of mitochondrial dysfunction.Receipt of nucleoside reverse-transcriptase inhibitors, especially stavudine and lamivudine, was associated with possible mitochondrial dysfunction in children with perinatal HIV infection. Further studies are warranted to elucidate potential mechanisms of nucleoside reverse-transcriptase inhibitor toxicities.

Objective To compare the rates of psychopathology in youths perinatally infected with HIV (N = 319) with a comparison sample of peers (N = 256) either HIV-exposed or living in households with HIV-infected family members. Method Participants were randomly recruited from 29 sites in the United States and Puerto Rico and completed an extensive battery of measures including standardized DSM-IV-referenced ratings scales. Results The HIV+ group was relatively healthy (73% with CD4% >25%), and 92% were actively receiving antiretroviral therapy. Youths with HIV (17%) met symptom and impairment criteria for the following disorders: attention-deficit/hyperactivity disorder (12%), oppositional defiant disorder (5%), conduct disorder (1%), generalized anxiety disorder (2%), separation anxiety disorder (1%), depressive disorder (2%), or manic episode (1%). Many youths with HIV (27%) and peers (26%) were rated (either self- or caregiver report) as having psychiatric problems that interfered with academic or social functioning. With the exception of somatization disorder, the HIV+ group did not evidence higher rates or severity of psychopathology than peers, although rates for both groups were higher than the general population. Nevertheless, self-awareness of HIV infection in younger children was associated with more severe symptomatology, and youths with HIV had higher lifetime rates of special education (44 vs 32%), psychopharmacological (23 vs 12%), or behavioral (27 vs 17%) interventions. Youth-caregiver agreement was modest, and youths reported more impairment. Conclusion HIV infection was not associated with differentially greater levels of current psychopathology; nevertheless, investigation of relations with developmental changes and specific illness parameters and treatments are ongoing.

BACKGROUND: Youths perinatally infected with HIV often receive psychotropic medication and behavioral treatment for emotional and behavioral symptoms. We describe patterns of intervention for HIV-positive youth and youth in a control group in the United States. METHODS: Three hundred nineteen HIV-positive youth and 256 controls, aged 6 to 17 years, enrolled in the International Maternal Adolescent AIDS Clinical Trials 1055, a prospective, 2-year observational study of psychiatric symptoms. One hundred seventy-four youth in the control group were perinatally exposed to HIV, and 82 youth were uninfected children living in households with HIV-positive members. Youth and their primary caregivers completed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–referenced symptom-rating scales. Children's medication and behavioral psychiatric intervention histories were collected at entry. We evaluated the association of past or current psychiatric treatment with HIV status, baseline symptoms, and impairment by using multiple logistic regression, controlling for potential confounders. RESULTS: HIV-positive youth and youth in the control group had a similar prevalence of psychiatric symptoms (61%) and impairment (14% to 15%). One hundred four (18%) participants received psychotropic medications (stimulants [14%], antidepressants [6%], and neuroleptic agents [4%]), and 127 (22%) received behavioral treatment. More HIV-positive youth than youth in the control group received psychotropic medication (23% vs 12%) and behavioral treatment (27% vs 17%). After adjusting for symptom class and confounders, HIV-positive children had twice the odds of children in the control group of having received stimulants and >4 times the odds of having received antidepressants. Caregiver-reported symptoms or impairment were associated with higher odds of intervention than reports by children alone. CONCLUSIONS: HIV-positive children are more likely to receive mental health interventions than control-group children. Pediatricians and caregivers should consider available mental health treatment options for all children living in families affected by HIV.

Survival of HIV-infected children continues to increase and the use of antiretrovirals (ARVs) is expanding; however there are few data regarding the incidence of renal dysfunction and associated risk factors among HIV-infected children and youth.A total of 2102 children enrolled in Pediatric AIDS Clinical Trials Group Study 219/219C, were followed and assessed prospectively for30 months. Occurrence of clinical events and laboratory abnormalities were recorded using standardized criteria and forms. Therapeutic decisions were made by clinicians at each site. Occurrence of persistent renal laboratory abnormalities was the main outcome measure.Four hundred forty-six (22%) enrollees exhibited at least one persistent renal laboratory abnormality. Elevated serum creatinine (Cr) was more common than persistent proteinuria (15% vs. 8%). The incidence of new renal laboratory abnormalities was 3.7 events per 100 person-years with rates increasing between 1993 and 2005. Older age (or=6 years vs.6 years), Hispanic ethnicity, and Black non-Hispanic race were associated with increased risk of renal dysfunction, but CDC clinical class and plasma HIV RNA levels were not. Subjects exposed to ARV regimens containing tenofovir and/or indinavir had approximately twice the risk of developing renal dysfunction compared with persons exposed to other ARVs. The risk of renal dysfunction was also elevated for other antivirals (hazard ratio = 5.4) and amphotericin B (hazard ratio = 28).Persistent renal function abnormalities occur frequently in HIV-infected children. Improved survival, Black race and Hispanic ethnicity, and exposure to tenofovir, indinavir, and other antimicrobial agents increase the risk for renal dysfunction. All HIV-infected children should be monitored closely for evidence of renal disease.

Objectives The relationship of specific psychiatric conditions to adherence has not been examined in longitudinal studies of youth with perinatal HIV infection (PHIV). We examined associations between psychiatric conditions and antiretroviral nonadherence over 2 years. Design Longitudinal study in 294 PHIV youth, 6-17 years old, in the United States and Puerto Rico. Methods We annually assessed three nonadherence outcomes: missed above 5% of doses in the past 3 days, missed a dose within the past month, and unsuppressed viral load (>400 copies/ml). We fit multivariable logistic models for nonadherence using Generalized Estimating Equations, and evaluated associations of psychiatric conditions (attention deficit hyperactivity disorder, disruptive behavior, depression, anxiety) at entry with incident nonadherence using multivariable logistic regression. Results Nonadherence prevalence at study entry was 14% (3-day recall), 32% (past month nonadherence), and 38% (unsuppressed viral load), remaining similar over time. At entry, 38% met symptom cut-off criteria for at least one psychiatric condition. Greater odds of 3-day recall nonadherence were observed at week 96 for those with depression [adjusted odds ratio (aOR) 4.14, 95% confidence interval (CI) 1.11-15.42] or disruptive behavior (aOR 3.36, 95% CI 1.02-11.10], but not at entry. Those with vs. without attention deficit hyperactivity disorder had elevated odds of unsuppressed viral load at weeks 48 (aOR 2.46, 95% CI 1.27-4.78) and 96 (aOR 2.35, 95% CI 1.01-5.45), but not at entry. Among 232 youth adherent at entry, 16% reported incident 3-day recall nonadherence. Disruptive behavior conditions at entry were associated with incident 3-day recall nonadherence (aOR 3.01, 95% CI 1.24-7.31). Conclusion In PHIV youth, comprehensive adherence interventions that address psychiatric conditions throughout the transition to adult care are needed.

Background Combination antiretroviral therapy (cART) has resulted in a dramatic decrease in human immunodeficiency virus (HIV)-related opportunistic infections and deaths in US youth, but both continue to occur. Methods We estimated the incidence of complications and deaths in IMPAACT P1074, a long-term US-based prospective multicenter cohort study conducted from April 2008 to June 2014. Incidence rates of selected diagnoses and trends over time were compared with those from a previous observational cohort study, P219C (2004-2007). Causes of death and relevant demographic and clinical features were reviewed. Results Among 1201 HIV-infected youth in P1074 (87% perinatally infected; mean [standard deviation] age at last chart review, 20.9 [5.4] years), psychiatric and neurodevelopmental disorders, asthma, pneumonia, and genital tract infections were among the most common comorbid conditions. Compared with findings in P219C, conditions with significantly increased incidence included substance or alcohol abuse, latent tuberculosis, diabetes mellitus, atypical mycobacterial infections, vitamin D deficiency or metabolic bone disorders, anxiety disorders, and fractures; the incidence of pneumonia decreased significantly. Twenty-eight deaths occurred, yielding a standardized mortality rate 31.5 times that of the US population. Those who died were older, less likely to be receiving cART, and had lower CD4 cell counts and higher viral loads. Most deaths (86%) were due to HIV-related medical conditions. Conclusions Opportunistic infections and deaths are less common among HIV-infected youth in the US in the cART era, but the mortality rate remains elevated. Deaths were associated with poor HIV control and older age. Emerging complications, such as psychiatric, inflammatory, metabolic, and genital tract diseases, need to be addressed.

Purpose: To assess the impact of a Balint-like physician awareness group on hematology-oncology fellows’ attitudes and measure changes in attitudes during the first fellowship year. Patients and Methods: We used a modified crossover design in which one half of a fellowship class at a time was exposed to the group intervention over a 2-year period (2000 to 2002). Two 14-fellow classes were followed for 1 year each and were given three “attitudes” questionnaires, at the beginning, middle, and end of the academic year. Results: Forty Balint group sessions were held during the 2-year study period; 82 questionnaires of the 84 administered (98%) were recovered. Instrument content and criterion validity were demonstrated, as was topic domain reliability. Overall, mean attitude scores increased following the group intervention, from 3.6 (95% CI, 3.5 to 3.7) to 3.7 (95% CI, 3.6 to 3.8; P = .09). Within domains, scores increased in a “fellow’s views of him/herself as a physician,” from 3.8 (95% CI, 3.6 to 3.9) to 4.1 (95% CI, 3.9 to 4.2; P = .008) and “comfort dealing with emotional patient/clinical situations,” from 3.5 (95% CI, 3.3 to 3.7) to 3.7 (95% CI, 3.6 to 3.9; P = .11). Changes in responses to individual questions included: an increase in fellows’ comfort with the technical aspects of being an oncologist (P < .03); an increase in fellows’ comfort with discussing the stress of home at work (P < .023); and an increase among fellows in feeling pressed for time to discuss psychosocial issues with patients (P = .035). Conclusion: A physician awareness group was feasible and enhanced fellows’ development as physicians. Further research is needed to determine how to incorporate such groups into oncology fellowships.

Older age is a strong predictor of accelerated human immunodeficiency virus (HIV) disease progression. We investigated the possible immunologic basis of this interaction by comparing older (>/=45 years) and younger (

As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care.To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status.Combining data from the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 multicenter cohort studies (March 2007 through April 2015), we estimated event rates during person-time spent in key strata of age (7-12, 13-17, and 18-30 years), CD4 cell count (200, 200-499, and ≥500/μL), and a combined measure of VL and ARV status (VL400 or ≥400 copies/mL; ARV therapy or no ARV therapy). A total of 1562 participants in the PHACS Adolescent Master Protocol and IMPAACT P1074 were eligible, and 1446 PHIVY from 41 ambulatory sites in the 12 US states, including Puerto Rico were enrolled. The dates of analysis were March 2015 through January 2017.Clinical event rates stratified by person-time in age, CD4 cell count, and VL and ARV categories.A total of 1446 PHIVY participated in the study (mean [SD] age, 14.6 [4.6] years; 759 female [52.5%]; 953 black [65.9%]). During a mean (SD) follow-up of 4.9 (1.3) years, higher incidences of CDC-B events, CDC-C events, and mortality were observed as participants aged. Older PHIVY (aged 13-17 and 18-30 years) spent more time with a VL of 400 copies/mL or more and with a CD4 cell count of less than 200/µL compared with 7- to 12-year-old participants (30% and 44% vs 22% of person-time with a VL≥400 copies/mL; 5% and 18% vs 2% of person-time with CD4 cell count200/µL; P .001 for each comparison). We observed higher rates of CDC-B events, CDC-C events, bacterial infections, and mortality at lower CD4 cell counts, as expected. The mortality rate among older PHIVY was 6 to 12 times that among the general US population. Higher rates of sexually transmitted infections were also observed at lower CD4 cell counts after adjusting for age.Older PHIVY were at increased risk of viremia, immunosuppression, CDC-B events, CDC-C events, and mortality. Interventions to improve ARV therapy adherence and optimize models of care for PHIVY as they age are urgently needed to improve long-term outcomes among PHIVY.

Obtaining accurate estimates of mental health problems among youth perinatally infected with HIV (PHIV) helps clinicians develop targeted interventions but requires enrollment and retention of representative youth into research studies.The study design for IMPAACT P1055, a US-based, multisite prospective study of psychiatric symptoms among PHIV youth and uninfected controls aged 6 to 17 years old, is described. Participants were compared with nonparticipants by demographic characteristics and reasons were summarized for study refusal. Adjusted logistic regression models were used to evaluate the association of psychiatric symptoms and other factors with loss to follow-up (LTFU).Among 2281 youth screened between 2005 and 2006 at 29 IMPAACT research sites, 580 (25%) refused to participate, primarily because of time constraints. Among 1162 eligible youth approached, 582 (50%) enrolled (323 PHIV and 259 Control), with higher participation rates for Hispanic youth. Retention at 2 years was significantly higher for PHIV than Controls (84% vs 77%, P = 0.03). In logistic regression models adjusting for sociodemographic characteristics and HIV status, youth with any self-assessed psychiatric condition had higher odds of LTFU compared with those with no disorder (adjusted odds ratio = 1.56, 95% confidence interval: 1.00 to 2.43). Among PHIV youth, those with any psychiatric condition had 3-fold higher odds of LTFU (adjusted odds ratio = 3.11, 95% confidence interval: 1.61 to 6.01).Enrollment and retention of PHIV youth into mental health research studies is challenging for those with psychiatric conditions and may lead to underestimated risks for mental health problems. Creative approaches for engaging HIV-infected youth and their families are required for ensuring representative study populations.

Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), disproportionately affect adolescents and young adults (AYAs) ages 13-24 years. Sexually transmitted infections likewise are a risk factor for HIV acquisition and transmission; however, there is a lack of data on STI acquisition in HIV-infected AYAs.We determined the incidence of STIs in HIV-infected AYAs 12.525 years of age in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 observational cohort study. Univariate and multivariable logistic regression models were used to evaluate the association of HIV control (mean viral load500 copies/mL and CD4+ T cells500 cells/mm3 in the year preceding STI diagnosis) and other risk factors with STI occurrence.Of 1201 enrolled subjects, 1042 participants met age criteria and were included (49% male, 61% black, 88% perinatally infected; mean age 18.3 years). One hundred twenty participants had at least 1 STI on study, of whom 93 had their first lifetime STI (incidence rate = 2.8/100 person-years). For individual STI categories, 155 incident category-specific events were reported; human papillomavirus (HPV) and chlamydial infections were the most common. In the multivariable model, having an STI was associated with older age (adjusted odds ratio [aOR] = 1.13; 95% confidence interval [CI], 1.05-1.22), female sex (aOR = 2.65; 95% CI, 1.67-4.21), nonperinatal HIV acquisition (aOR = 2.33; 95% CI, 1.29-4.22), and uncontrolled HIV infection (aOR = 2.05; 95% CI, 1.29-3.25).Sexually transmitted infection acquisition in HIV-infected AYAs is associated with older age, female sex, nonperinatal HIV acquisition, and poorly controlled HIV infection. Substantial rates of STIs among HIV-infected AYAs support enhanced preventive interventions, including safe-sex practices and HPV vaccination, and antiretroviral adherence strategies.

The influence of disease severity on cognitive and adaptive functioning in perinatally HIV-infected youth with (PHIV+/C) and without (PHIV+/NoC) a previous AIDS-defining illness (Centers for Disease Control and Prevention Class C event), compared with perinatally HIV-exposed but uninfected youth (PHEU) is not well understood.This was a cross-sectional analysis of cognitive and adaptive functioning in PHIV+/C (n = 88), PHIV+/NoC (n = 270) and PHEU (n = 200) youth aged 7-16 years, from a multisite prospective cohort study. Youth and caregivers completed the Wechsler Intelligence Scale for Children, Fourth Edition and the Adaptive Behavior Assessment System, Second Edition, respectively. We compared means and rates of impairment between groups, and examined associations with other psychosocial factors.Overall mean scores on measures of cognitive and adaptive functioning were in the low average range for all 3 groups. After adjustment for covariates, mean full-scale intelligence quotient scores were significantly lower for the PHIV+/C group than the PHIV+/NoC and PHEU groups (mean = 77.8 versus 83.4 and 83.3, respectively), whereas no significant differences were observed between the PHEU and PHIV+/NoC groups in any domain. Lower cognitive performance for the PHIV+/C group was primarily attributable to a prior diagnosis of encephalopathy. No significant differences between groups were observed in adaptive functioning.For long-term survivors, youth with HIV infection and a prior Centers for Disease Control and Prevention Class C event have higher risk for cognitive but not adaptive impairment regardless of current health status; this finding appears attributable to a previous diagnosis of encephalopathy. Early preventive therapy may be critical in reducing risk of later neurodevelopmental impairments.

Objective To evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection. Design Cross-sectional analysis of entry data from an observational, prospective 2-year study. Logistic and linear regression models adjusted for potential confounders were used. Setting Twenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico. Participants Youth aged 6 to 17 years who had HIV infection (N = 319). Main Exposures Antiretroviral treatment and perinatal HIV infection. Main Outcome Measures Youth and primary caregivers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social, and academic functioning; and quality of life. Results Characteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms, older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms, higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage at study entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms. A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning. Conclusion Human immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic, and social functioning, all of which warrant additional study. Trial Registration clinicaltrials.gov Identifier: NCT00100542

Drug use in combination with psychiatric illness may lead to unsafe sexual risk behavior and increased risk for secondary HIV transmission among adolescents with HIV infection. We compared the prevalence of substance use for perinatally HIV-infected youth to uninfected adolescents living in families affected by HIV infection, and evaluated the association of psychiatric symptoms with risk of substance use. Among 299 adolescents (196 HIV+, 103 HIV-) aged 12-18 years enrolled in IMPAACT P1055, a multisite US cohort study, 14% reported substance use at enrollment (HIV+: 13%, HIV-: 16%). In adjusted logistic regression models, adolescents had significantly higher odds of substance use if they met symptom criteria for ADHD [adjusted odds ratio (aOR) = 2.7, Wald χ(2) = 5.18, P = 0.02], major depression or dysthymia (aOR = 4.0, Wald χ(2) = 7.36, P = 0.01), oppositional defiant disorder (aOR = 4.8, Wald χ(2) = 12.7, P = 0.001), or conduct disorder (aOR = 15.4, Wald χ(2) = 28.12, P = 0.001). Among HIV-infected youth, those with lower CD4 lymphocyte percentage (CD4% 25%) had significantly increased risk of substance use (aOR = 2.7, Wald χ(2) = 4.79, P = 0.03). However, there was no overall association of substance use with HIV infection status, and the association between psychiatric symptoms and substance use did not differ by HIV status. Programs to prevent substance use should target both HIV-infected and uninfected adolescents living in families affected by HIV infection, particularly those with psychiatric symptoms.

This cross-sectional study evaluated the prevalence of pain and psychiatric symptoms in perinatally HIV-infected children at entry into P1055, a multicenter investigation of the prevalence and severity of psychiatric symptoms in HIV-infected children. Subjects 6–17 years of age and their primary caregivers were recruited from 29 International Maternal Pediatric Adolescent AIDS Clinical Trials sites in the USA and Puerto Rico. A total of 576 children (320 HIV+ and 256 HIV− children) were enrolled from June 2005 to September 2006. Subject self-reports of pain were measured by the Wong–Baker visual analog scale and Short-Form McGill Pain Questionnaire. Symptomatology for anxiety, depression, and dysthymia was assessed through Symptom Inventory instruments. Caregiver's assessment of their child's pain and psychiatric symptomatology was similarly measured. Logistic regression models were used to evaluate predictors of pain. We found that a higher proportion of HIV-infected than uninfected subjects reported pain in the last two months (41% vs 32%, p=0.04), last two weeks (28% vs 19%, p=0.02), and lasting more than one week (20% vs 11%, p=0.03). Among HIV-infected youth, females (OR=1.53, p=0.09), White race (OR=2.15, p=0.04), and Centers for Disease Control (CDC) Class C (OR=1.83, p=0.04) were significantly more likely to report pain. For all subjects, only 52% of caregivers recognized their child's pain and just 22% were aware that pain affected their child's daily activities. The odds of reported pain in HIV+ increased with higher symptom severity for generalized anxiety (OR=1.14, p=0.03), major depression (OR=1.15, p=0.03), and dysthymia (OR=1.18, p=0.01). This study underscores the importance of queries concerning pain and emotional stressors in the care of HIV+ and uninfected children exposed to HIV+ individuals. The discordance between patient and caregiver reports of pain and its impact on activities of daily living highlights that pain in children is under-recognized and therefore potentially under-treated.

A pilot study of South Vietnamese ex-political detainees who had been incarcerated in Vietnamese reeducation camps and resettled in the United States disclosed significant mental health problems associated with torture and traumatic head injury (THI).To identify structural brain alterations associated with THI and to investigate whether these deficits are associated with posttraumatic stress disorder and depression.Cross-sectional neuroimaging study.Massachusetts General Hospital and McLean Hospital.A subsample of Vietnamese ex-political detainees (n = 42) and comparison subjects (n = 16) selected from a community study of 337 ex-political detainees and 82 comparison subjects.Scores on the Vietnamese versions of the Hopkins Symptom Checklist-25 (HSCL) and Harvard Trauma Questionnaire for depression and posttraumatic stress disorder, respectively; cerebral regional cortical thickness; and manual volumetric morphometry of the amygdala, hippocampus, and thalamus.Ex-political detainees exposed to THI (n = 16) showed a higher rate of depression (odds ratio, 10.2; 95% confidence interval, 1.2-90.0) than those without THI exposure (n = 26). Ex-political detainees with THI had thinner prefrontotemporal cortices than those without THI exposure (P.001 by the statistical difference brain map) in the left dorsolateral prefrontal and bilateral superior temporal cortices, controlling for age, handedness, and number of trauma/torture events (left superior frontal cortex [SFC], P = .006; left middle frontal cortex, P = .01; left superior temporal cortex [STC], P = .007; right STC, P = .01). Trauma/torture events were associated with bilateral amygdala volume loss (left, P = .045; right, P = .003). Cortical thinning associated with THI in the left SFC and bilateral STC was related to HSCL depression scores in THI-exposed (vs non-THI-exposed) ex-political detainees (left SFC, P for interaction = .007; left STC, P for interaction = .03; right STC, P for interaction = .02).Structural deficits in prefrontotemporal brain regions are linked to THI exposures. These brain lesions are associated with the symptom severity of depression in Vietnamese ex-political detainees.

Objective To estimate highly active antiretroviral therapy (HAART)–era incident rates for the first episode of noninfectious conditions in human immunodeficiency virus (HIV)–infected youth in order to identify HAART-era changes in the natural history of perinatal HIV infection. Design Multicenter prospective cohort study. Setting More than 80 sites in the United States including Puerto Rico. Patients Perinatally HIV-infected youth. Main Outcome Measures Incidence rates (IRs) per 100 person-years were calculated for targeted noninfectious conditions occurring in perinatally HIV-infected children. A χ 2 test for linear trend was used to evaluate changes in the rates from 2001 to 2006. Results Two thousand five hundred seventy-five perinatally HIV-infected children (51%, female; 59%, black, non-Hispanic) were enrolled in Pediatric AIDS Clinical Trials Group (PACTG) 219C between 2000 and 2006 and were followed up for a median of 59 months. The 10 most common noninfectious conditions were pregnancy conditions (IR = 6.16; 95% confidence interval (CI), 3.9-9.3), birth defects (IR = 0.19; 95% CI, 0.1-0.3), gynecological dysplasias (IR = 5.92; 95% CI, 3.9-8.6), condyloma (IR = 0.15; 95% CI, 0.1-0.2), encephalopathy (IR = 0.38; 95% CI, 0.3-0.5), pancreatitis (IR = 0.30; 95% CI, 0.2-0.4), cardiac disorders (IR = 0.28; 95% CI, 0.2-0.4), renal disorders (IR = 0.26; 95% CI, 0.2-0.4), peripheral neuropathy (IR = 0.23; 95% CI, 0.2-0.4), and idiopathic thrombocytic purpura (IR = 0.15; 95% CI, 0.1-0.3). Among these conditions, 5 showed significant trends, with IRs increasing over time in pregnancy-related conditions ( P P = .02) while IRs decreased over time for encephalopathy ( P P = .002), and cardiac disorders ( P = .007). Conclusions Between 2001 and 2006, the incidence for 3 conditions decreased and increased for 2 others, demonstrating the change in medical issues and conditions in perinatally infected youth. Continued surveillance with appropriate tools will be needed to assess the long-term effects of HAART and HIV as well as development of new noninfectious conditions of HIV.

ContextCombination anti-retroviral therapy or highly active antiretroviral therapy (HAART) has resulted in a dramatic decline in the incidence of opportunistic and other infections in human immunodeficiency virus (HIV)–infected adults and children.ObjectivesTo estimate the incidence of 29 targeted opportunistic and other infections occurring in the era of HAART—between January 1, 2001, and December 31, 2004—in HIV-infected infants, children, and adolescents followed up in Pediatric AIDS Clinical Trials Group (PACTG) 219C; to compare incidence rates in the HAART era to those of the pre-HAART era; and to test for linear trends over time in the HAART era.Design, Setting, and ParticipantsOngoing, multicenter, prospective cohort study designed to examine long-term outcomes in HIV-infected children. The study population included 2767 children enrolled between September 15, 2000, and December 31, 2004, with information entered in the database up to August 1, 2005, when data analysis was conducted. The pre-HAART era comparison population included 3331 children enrolled in 13 PACTG protocols from October 1988 to August 1998.Main Outcome MeasuresFirst occurrence of each of the 29 targeted infections.ResultsSeventy-five percent of the children were enrolled in 2000 and 2001, 90% acquired HIV perinatally, 52% were girls, and 59% were black. The median age was 8.2 years (range, 6-13 years). The median duration of follow-up was 3.4 years. Overall, 553 first episodes of a specific infection occurred among 395 (14%) of the study participants. The number of events for the 4 most common first-time infections and their incidence rates (IRs) per 100 person-years were 123 bacterial pneumonia (IR, 2.15; 95% confidence interval [CI], 1.79-2.56), 77 herpes zoster (IR, 1.11; 95% CI, 0.88-1.39), 57 dermatophyte infections (IR, 0.88; 0.67-1.14), and 52 oral candidiasis (IR, 0.93; 95% CI, 0.70-1.22). Incidence rates of first bacteremia, Pneumocystisjeroveci pneumonia, disseminated Mycobacteriumavium complex, lymphoid interstitial pneumonitis, systemic fungal infection, cytomegalovirus retinitis, and tuberculosis were all less than 0.50 per 100 person-years. There were no statistically significant linear trends in incidence for any of the 29 infections over the 4 calendar years. However, infection rates were significantly lower than those reported in the PACTG in the pre-HAART era. The pre-HAART IRs were as follows: for bacterial pneumonia, IR, 11.1; 95% CI, 10.3-12.0; bacteremia, IR, 3.3; 95% CI, 2.9-3.8; herpes zoster, IR, 2.9; 95% CI, 2.6-3.3; disseminated Mavium complex, IR, 1.8; 95% CI, 1.5-2.1; Pjeroveci, IR, 1.3; 95% CI, 1.1-1.6; oral candidiasis, IR, 1.2; 95% CI, 1.0-1.5; cytomegalovirus retinitis, IR, 0.5; 95% CI, 0.3-0.6; and tuberculosis, IR, 0.2; 95% CI, 0.1-0.4.ConclusionsOpportunistic infections and other related infections are uncommon in children in the HAART era, and infection rates continue to be lower than those reported in the pre-HAART era. Continued surveillance is important to assess the long-term effect of HAART on the occurrence of opportunistic and other related infections in children.

The cellulose/pectin combination (C/P) investigated in this study is as efficacious as a psyllium seed product widely used as a bulk laxative. Because of its physical characteristics (whiteness, lack of flavor and odor, lack of gelling upon standing), it is easy to use as a component of baked foods, sauces, drinks, stews, and in other recipes. Given its fecal bulking equivalence to the popular psyllium-based products, C/P offers advantages to the patient who takes a bulking agent regularly because of the wide choice of methods of consumption, ensuring better compliance over long periods of time. This cellulose/pectin combination appears to be a viable alternative to the limited choice presently available to the bulk laxative user and could also be used as a plant fiber supplement whenever this is desirable.

Some relationships have been proposed between fecal volatile fatty acids, transit time, fecal weight, and dietary fiber intake. In this study, the effect of purified cellulose, purified pectin, and a natural low-residue diet on fecal acetic, propionic, butyric, isobutyric, valeric and isovaleric acids, transit time, and fecal weight was investigated. Forty-two healthy male and female adults were fed low-residue diets for 2 weeks, followed by 3 weeks on the same diet plus either 14 g/day cellulose or 6 g/day pectin or a sucrose placebo. Feces were collected for 7 days during weeks 2 and 5. From week 2 to 5, transit time decreased by 2.5 days with cellulose, 0.2 with placebo, and increased by 0.1 with pectin; fecal weight increased by 34 g/day with cellulose but decreased by 15 g/day with placebo and by 0.32 g/day with pectin (P < 0.05); volatile fatty acids decreased with placebo (-1.2 g/7 days), but increased with cellulose (+ 1.3 g/7 days) and pectin (+0.6 g/7 days) (P < 0.05). Volatile fatty acid changes with placebo and cellulose paralleled changes in fecal weight, thus fecal volatile fatty acid concentration did not change. Conversely, volatile fatty acid increase of the pectin group was not paralleled by fecal weight increase, signifying an increase in volatile fatty acid concentration (P < 0.05) of possible physiological significance. Some volatile fatty acids are probably absorbed, a fact worthy of further investigation. This study confirms: 1) that generalization of the effects of dietary fiber on volatile fatty acids, fecal weight and transit time should be avoided, 2) the mild antidiarrheal effect of pectin and, 3) the bulkung properties of cellulose. Am. J. Clin. Nutr. 33: 754-759, 1980.