Publications by authors named "Chaiwat Ngampiyaskul"

27 Publications

  • Page 1 of 1

HIV-related enacted stigma and increase frequency of depressive symptoms among Thai and Cambodian adolescents and young adults with perinatal HIV.

Int J STD AIDS 2021 Mar 18;32(3):246-256. Epub 2020 Dec 18.

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Center, Bangkok, Thailand.

HIV-related enacted stigma and social problems may increase risk for depression and/or behavioral problems among adolescents and young adults with perinatal HIV(AYA-PHIV), yet few studies have explored stigma in AYA-PHIV residing in low-to-middle income regions, including Southeast Asia. We assessed HIV-related enacted stigma and social problems in AYA-PHIV who participated in the RESILIENCE study (clinicaltrials.gov identification: U19AI53741) in Thailand and Cambodia using specific questions during structured in-person interviews. Depression was measured by the Child Depression Inventory for children <15 years, or the Center for Epidemiologic Studies Depression Scales for youth ≥15 years); behavioral problems were measured by the Child Behavior Checklist (CBCL-caregiver report). Among 195 AYA-PHIV (median age 16.9 years), 25.6% reported a lifetime experience of enacted stigma, while 10.8% experienced social problems due to HIV infection. The frequency of depressive symptoms was nearly two-fold higher among AYA-PHIV with compared to those without HIV-related enacted stigma (34.7% vs. 16.0%, p = 0.005). Caregiver-reported behavioral problems were detected in 14.6% of all AYA-PHIV, with no differences between those with and without HIV-related enacted stigma. Low household income and caregiver mental health problems were independent risk factors for depressive symptoms; HIV-related enacted stigma was also associated with increased risk, warranting targeted services to support AYA-PHIV.
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http://dx.doi.org/10.1177/0956462420960602DOI Listing
March 2021

Machine-learning classification of neurocognitive performance in children with perinatal HIV initiating de novo antiretroviral therapy.

AIDS 2020 04;34(5):737-748

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center.

Objective: To develop a predictive model of neurocognitive trajectories in children with perinatal HIV (pHIV).

Design: Machine learning analysis of baseline and longitudinal predictors derived from clinical measures utilized in pediatric HIV.

Methods: Two hundred and eighty-five children (ages 2-14 years at baseline; Mage = 6.4 years) with pHIV in Southeast Asia underwent neurocognitive assessment at study enrollment and twice annually thereafter for an average of 5.4 years. Neurocognitive slopes were modeled to establish two subgroups [above (n = 145) and below average (n = 140) trajectories). Gradient-boosted multivariate regressions (GBM) with five-fold cross validation were conducted to examine baseline (pre-ART) and longitudinal predictive features derived from demographic, HIV disease, immune, mental health, and physical health indices (i.e. complete blood count [CBC]).

Results: The baseline GBM established a classifier of neurocognitive group designation with an average AUC of 79% built from HIV disease severity and immune markers. GBM analysis of longitudinal predictors with and without interactions improved the average AUC to 87 and 90%, respectively. Mental health problems and hematocrit levels also emerged as salient features in the longitudinal models, with novel interactions between mental health problems and both CD4 cell count and hematocrit levels. Average AUCs derived from each GBM model were higher than results obtained using logistic regression.

Conclusion: Our findings support the feasibility of machine learning to identify children with pHIV at risk for suboptimal neurocognitive development. Results also suggest that interactions between HIV disease and mental health problems are early antecedents to neurocognitive difficulties in later childhood among youth with pHIV.
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http://dx.doi.org/10.1097/QAD.0000000000002471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072001PMC
April 2020

Impact of antiretroviral treatment on height evolution of HIV infected children.

BMC Pediatr 2019 08 17;19(1):287. Epub 2019 Aug 17.

Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France.

Background: Antiretroviral treatment (ART) has been shown to have a beneficial effect on the weight evolution but its effect on height remains unclear. We described patterns of height evolution and identified predictors of catch-up growth in HIV-infected children on ART.

Methods: To describe the height evolution from birth to adulthood, we developed a nonlinear mixed effect model using data from perinatally HIV-infected children who initiated ART from 1999 to 2013 in a prospective cohort study in Thailand. The main covariates of interest were: sex, ART regimen (dual nucleoside reverse-transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based), baseline CD4 percentage, HIV-RNA load and CDC HIV Classification stage and occurrence of AIDS-defining events.

Results: A total 477 children (43% boys) contributed 18,596 height measurements over a median duration of 6.3 years on ART (interquartile range, 3.0 to 8.3). At ART initiation, median age was 6.2 years (1.8 to 9.6), 16% of children were underweight (weight-for-age z-score < - 2), 49% presented stunting (height-for-age z-score < - 2), and 7% wasting (weight-for-height z-score < - 2). The most frequent regimen at ART initiation was NNRTI-based (79%). A model with 4 components, birth length and 3 exponential functions of age accounting for the 3 growth phases was developed and show that the height-growth velocity was inversely associated with the age at ART initiation, the adult height was significantly lower in those who had experienced at least one AIDS-defining event while, as expected, the model found that adult height in females was lower than in males. Age at ART initiation, type of ART regimen, CDC stage, CD4 percentages, and HIV-RNA load were not associated with the final height.

Conclusions: The younger the children at ART initiation, the greater the effect on height-growth velocity, supporting the World Health Organization's recommendation to start ART as early as possible. However, final adult height was not linked to the age at ART initiation.
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http://dx.doi.org/10.1186/s12887-019-1663-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697969PMC
August 2019

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

AIDS 2019 06;33 Suppl 1:S17-S27

HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute, Columbia University, New York, New York, USA.

Objectives: Psychosocial challenges associated with perinatally acquired HIV (PHIV) infection are well known, yet many children infected with HIV since birth demonstrate positive outcomes, referred to as resilience. The purpose of this study was to evaluate emotional-behavioral development and identify salient predictors of resilience among long-term survivors of PHIV.

Design: Prospective investigation of children with PHIV compared with demographically similar perinatally HIV-exposed but uninfected (PHEU) and HIV-unexposed, uninfected (HUU) children, all from Thailand and Cambodia.

Methods: The Child Behavior Checklist (CBCL; parent version) was administered at baseline and annual follow-up visits (median follow-up of 3 years) to children age 6-14. Resilience was defined as consistent CBCL scores on the Internalizing, Externalizing or Total Problem T scales within normative ranges (T-scores <60) at every time point. Generalized estimating equations examined CBCL scores over time and logistic models examined demographic, socioeconomic, and cultural predictors of resilience.

Results: Participants included 448 children (236 PHIV, 98 PHEU, 114 HUU), with median (interquartile range) age at first evaluation of 7 (6-9) years. Children with PHIV exhibited similar rates of resilience as PHEU and HUU on the Externalizing and Total Problems scales. Resilience on the Internalizing scale was more likely in PHEU (71%) compared with PHIV (59%) or HUU (56%), P = 0.049. Factors associated with resilience in adjusted models included: HIV-exposed but uninfected status, higher household income, Cambodian nationality, female sex, and caregiver type.

Conclusion: Despite biopsychosocial risks, resilience is observed among PHIV and PHEU children. Further study is needed to understand mechanisms underlying associated factors and intervention priorities.
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http://dx.doi.org/10.1097/QAD.0000000000002182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799438PMC
June 2019

Increased Risk of Executive Function and Emotional Behavioral Problems Among Virologically Well-Controlled Perinatally HIV-Infected Adolescents in Thailand and Cambodia.

J Acquir Immune Defic Syndr 2019 11;82(3):297-304

HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute, and Columbia University, New York, NY.

Background: Large numbers of perinatally HIV-infected (PHIV) children are aging into adolescence. We examined cognitive and behavioral outcomes in a longitudinal cohort of Asian youth.

Methods: We followed up 231 PHIV, 125 perinatally HIV-exposed, uninfected (HEU), and 138 HIV-unexposed, uninfected (HUU) adolescents (aged 10 years and older), matched by age/sex, in Thailand and Cambodia for 3 years. Executive function was assessed with Children's Color Trails Tests 1 and 2 (CCTT-1 and -2), the design fluency test, and the verbal fluency test. Working memory (Freedom from Distractibility Index) and processing speed index were assessed using WISC-III. Visual memory was assessed by design memory and design recognition subtests of the Wide Range Assessment of Memory and Learning (WRAML-2) and behavioral problems using the Child Behavior Checklist (CBCL). Generalized estimating equations examined adjusted odds ratios of cognitive impairment (Z-scores ≥2 SD below age-adjusted means of the HUU group) and CBCL T-scores in the borderline-clinical range (T-Scores ≥60) in PHIV and HEU versus HUU youth, adjusting for ethnicity, household income, and caregiver characteristics.

Results: The median age at enrollment was 13.8 years, with 58% women and 63% Thai participants. PHIV youth had >86% virological suppression and significantly higher impairment rates on CCTT-1 and -2 tests, design fluency test, verbal fluency tests, design memory, and CBCL internalizing and externalizing problems. Results were mostly similar between HEU and HUU groups, apart from higher impairment rates on CCTT-1 and internalizing problems in HEU.

Conclusion: Asian adolescents with PHIV remain at risk of cognitive and mental health problems despite HIV treatment. Selective risks are observed among HEU youth.
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http://dx.doi.org/10.1097/QAI.0000000000002132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814288PMC
November 2019

Cognition, Emotional Health, and Immunological Markers in Children With Long-Term Nonprogressive HIV.

J Acquir Immune Defic Syndr 2018 04;77(4):417-426

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand.

Background: HIV-infected children with long-term nonprogressive (LTNP) disease eventually convert to a progressive disease type, yet the extent to which these children experience the cognitive and emotional symptoms observed in typical progressive HIV (Progressors) is unknown.

Methods: Eighty-eight LTNPs, 53 Progressors, and 323 healthy controls completed annual assessments of cognitive and emotional health as part of a prospective study. The 2 HIV-infected groups and the healthy controls were matched on age and sex distribution at enrollment. Plasma HIV RNA, T-cell counts/percentages, activated monocytes, perivascular monocytes, and markers of macrophage activation (sCD163 and sCD14) were compared by progression subtype. Cognitive and emotional outcomes were compared using cross-sectional linear regression analysis and longitudinal sensitivity models.

Results: LTNPs exhibited the same cognitive phenotype and emotional dysregulation as Progressors, with worse outcomes in both groups compared with controls. In addition, cognitive and emotional symptoms were evident before children reached the minimum age for LTNP designation (8 years). Baseline plasma HIV RNA, sCD163, activated monocytes, and perivascular monocytes were lower in LTNPs versus Progressors, with no difference in T-cell counts/percentages or sCD14 levels. Most LTNPs converted to a progressive disease subtype during the study, with similar cognitive and emotion profiles between these subgroups.

Conclusions: Pediatric LTNPs experience cognitive and emotional difficulties that mirror symptoms of progressive disease. The abnormalities are present at young ages and persist independent of plasma T-cell counts. The findings highlight the neurodevelopmental risk of pediatric HIV, even in those with early innate disease control.
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http://dx.doi.org/10.1097/QAI.0000000000001619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825279PMC
April 2018

Structural Neuroimaging and Neuropsychologic Signatures in Children With Vertically Acquired HIV.

Pediatr Infect Dis J 2018 07;37(7):662-668

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand.

Background: Children with vertically acquired HIV exhibit persistent cognitive impairments, yet the corresponding neuroimaging signature of vertical infection remains unclear.

Methods: Fifty healthy control children and 51 vertically infected children were included in the study. The HIV-infected group consisted of survivors who had not received antiretroviral therapy at birth. The HIV-infected group averaged 11.4 (2.5) years of age, with a median CD4 count of 683 cells/mm(3). Most (71%) of the HIV-infected children were on antiretroviral therapy for a median of 34 months (range: 33-42) with HIV RNA <40 copies/mL in 89% of the sample. The HIV-uninfected group averaged 10.6 (2.6) years of age. Magnetic resonance imaging was acquired to determine volumes of the caudate, putamen, thalamus, pallidum, hippocampus, nucleus accumbens, total white matter, total gray matter and cortical gray matter. Correlational analyses examined the degree of shared variance between brain volumes and both cognitive performances and laboratory markers of disease activity (T cells and plasma viral load).

Results: HIV-infected children exhibited larger volumes of the caudate, nucleus accumbens, total gray matter and cortical gray matter when compared with the controls. Volumetric differences were predominately evident in children under 12 years of age. HIV-infected children performed worse than controls on most neuropsychologic tests, though neither cognitive performances nor laboratory markers corresponded to brain volumes in the HIV-infected children.

Conclusions: Outcomes of the present study suggest abnormal brain maturation among HIV-infected pediatric survivors. Longitudinal studies of brain integrity and related resilience factors are needed to determine the impact of neuroimaging abnormalities on psychosocial function in pediatric HIV.
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http://dx.doi.org/10.1097/INF.0000000000001852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984109PMC
July 2018

Brief Report: AIDS-Defining Events and Deaths in HIV-Infected Children and Adolescents on Antiretrovirals: A 14-Year Study in Thailand.

J Acquir Immune Defic Syndr 2018 01;77(1):17-22

Institut de recherche pour le développement (IRD) UMI 174-PHPT, Marseille, France.

Background: Data are scarce on the long-term clinical outcomes of perinatally HIV-infected children and adolescents receiving antiretroviral therapy (ART) in low/middle-income countries. We assessed the incidence of mortality before (early) and after (late) 6 months of ART and of the composite outcome of new/recurrent AIDS-defining event or death >6 months after ART start (late AIDS/death) and their associated factors.

Methods: Study population was perinatally HIV-infected children (≤18 years) initiating ART within the Program for HIV Prevention and Treatment observational cohort (NCT00433030). Factors associated with late AIDS/death were assessed using competing risk regression models accounting for lost to-follow-up and included baseline and time-updated variables.

Results: Among 619 children, "early" mortality incidence was 99 deaths per 1000 person-years of follow-up [95% confidence interval (CI): 69 to 142] and "late" mortality 6 per 1000 person-years of follow-up (95% CI: 4 to 9). Of the 553 children alive >6 months after ART initiation, median age at ART initiation was 6.4 years, CD4% 8.2%, and HIV-RNA load 5.1 log10 copies/mL. Thirty-eight (7%) children developed late AIDS/death after median time of 3.3 years: 24 died and 24 experienced new/recurrent AIDS-defining events (10 subsequently died). Factors independently associated with late AIDS/death were current age ≥13 years (adjusted subdistribution hazard ratio 4.9; 95% CI: 2.4 to 10.1), HIV-RNA load always ≥400 copies/mL (12.3; 95% CI: 4.0 to 37.6), BMI-z-score always <-2 SD (13.7; 95% CI: 3.4 to 55.7), and hemoglobin <8 g/dL at least once (4.6; 95% CI: 2.0 to 10.5).

Conclusions: After the initial 6 months of ART, being an adolescent, persistent viremia, poor nutritional status, and severe anemia were associated with poor clinical outcomes. This supports the need for novel interventions that target children, particularly adolescents with poor growth and uncontrolled viremia.
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http://dx.doi.org/10.1097/QAI.0000000000001571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047734PMC
January 2018

Strategies to improve the uptake of effective contraception in perinatally HIV-infected adolescents.

J Virus Erad 2017 Jul 1;3(3):152-156. Epub 2017 Jul 1.

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand.

Objective: To assess strategies to improve safe-sex practices in sexually active female adolescents living with HIV, through linking reproductive health (RH) care with HIV care.

Methods: A single arm, 48-week prospective study was conducted with 77 sexually active adolescents in five sites in Thailand. Guided RH education was carried out through video, brochures and individual counselling. Participants were offered free effective contraception (EC), in addition to a barrier method (dual contraception) versus barrier method only. Changes in EC use were assessed with McNemar's test; predicting factors with logistic regression.

Results: Median age was 19 years; 95% were perinatally infected; 30% had been pregnant. All but one showed RH-knowledge improvement after RH education. Individual counselling was most often rated the 'most helpful' educational method. At the screening visit 21% were using dual contraception; 53% a male condom only; 8% EC method only; and 18% were not using any contraceptive method. Dual-contraception use improved with time, reaching 74% at week 48. EC-use at the baseline visit was associated with having ever used EC prior to study entry (<0.0001), and the study site (<0.0001). Having ever used EC was associated with a history of pregnancy (=0.0085) and forced sex (=0.0386).

Conclusion: Offering continuous RH care, linked with HIV care, resulted in increased use of dual contraception. Healthcare providers played a significant role in the process. RH education should address the main predictors for EC use by adolescents, including past, personal experience.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518244PMC
July 2017

Carbohydrate, lipid, bone and inflammatory markers in HIV-positive adolescents on antiretroviral therapy and hormonal contraception.

J Virus Erad 2017 Jan 1;3(1):56-60. Epub 2017 Jan 1.

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand; SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Background: Little is known about the cumulative effect of HIV antiretroviral therapy (ART) and hormonal contraception (HC) on metabolism and inflammation in HIV-positive women.

Methods: We conducted a cross-sectional assessment of markers for carbohydrate, lipid, bone metabolism, inflammation and coagulation in HIV-positive adolescents on ART and HC (=37) versus on ART only (=51) in Thailand. The Wilcoxon rank-sum test was used to assess differences between groups.

Results: The median age was 19.5 years. Most adolescents (95%) were perinatally infected. All were on ART for a median of 9 years. HC used was progestin only (=21); combined oral contraceptive (COC) tablets (=6) for the whole study period or alternating between progestin only and COC (=10). Prevalence of any metabolic abnormalities was 99%. Four biomarkers were significantly higher with HC no HC: insulin (10.3 6.2 μU/mL, =0.002), insulin resistance (1.89 1.19 mass units, =0.005), 25-OH vitamin D (33.2 20.2 ng/mL, <0.0001) and C-terminal telopeptide (690 530 ng/L, =0.011). Triglycerides and D-dimer were significantly lower with HC (103 139 mg/dL, =0.014 and 140 155 ng/mL, =0.003, respectively). There was no relationship between the type of HC or ART and the above differences.

Conclusion: Perinatally infected HIV-positive adolescents on ART in this pilot study had a high prevalence of metabolic abnormalities. Bone turnover markers and insulin resistance were significantly higher with HC. Research on the cumulative effect of HIV, ART and HC on metabolism and inflammation in adolescents with HIV is important in order to devise strategies for preventing and mitigating long-term comorbidities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337422PMC
January 2017

Incidence of Tuberculosis and Associated Mortality in a Cohort of Human Immunodeficiency Virus-Infected Children Initiating Antiretroviral Therapy.

J Pediatric Infect Dis Soc 2017 Jun;6(2):161-167

Institut de Recherche Pour le Développement, Unité Mixte Internationale 174-Program for HIV Prevention and Treatment, Marseille, France.

Background.: We assessed the incidence of tuberculosis, risk factors for tuberculosis, and the contribution of tuberculosis on mortality in a large cohort of human immunodeficiency virus (HIV)-infected children <15 years of age initiating first-line antiretroviral therapy (ART) between 1999 and 2012 in Thailand, one of the 22 high tuberculosis burden countries.

Methods.: A physician reviewed and classified tuberculosis cases. Incidence was the number of children with incident tuberculosis, defined as a first or recurrent tuberculosis diagnosis >30 days after ART initiation, divided by the total person-years of follow-up (PYFU). Risk factors for incident tuberculosis were identified using Fine and Gray's competing risks models, with death from other causes treated as a competing event, and risk factors for death were identified using Cox models.

Results.: At ART initiation, 670 children (55% female) had a median age of 6.4 years (interquartile range, 2.0-9.6), body mass index-for-age z-score -0.8 (-1.9 to 0.0), HIV ribonucleic acid viral load 5.1 log10 copies/mL (4.6-5.6), and CD4 9% (3-17). Median duration of follow-up was 7.7 years. Tuberculosis incidence was 7 per 1000 PYFU (95% confidence interval [CI], 5-11) and decreased with ART duration. Lower age-adjusted hemoglobin, hematocrit, and CD4 at ART initiation were associated with a higher risk of incident tuberculosis. Of the 30 incident tuberculosis cases, 9 died. Diagnosis of incident tuberculosis was associated with mortality (unadjusted hazard ratio = 10.2, 95% CI = 4.8-21.5, P < .001 and adjusted hazard ratio = 5.4, 95% CI = 2.5-11.7, P < .001).

Conclusions.: Incident tuberculosis was strongly associated with mortality. CD4 counts or hemoglobin or hematocrit levels may prompt clinicians to consider a possible tuberculosis infection.
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http://dx.doi.org/10.1093/jpids/piw090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907848PMC
June 2017

Soluble CD163 and monocyte populations in response to antiretroviral therapy and in relationship with neuropsychological testing among HIV-infected children.

J Virus Erad 2015;1(3):196-202. Epub 2015 Jun 30.

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand; Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Monocytes play a central role in HIV neuropathogenesis, but there are limited data on monocyte subsets and markers of monocyte activation in perinatally HIV-infected children.

Objective: To determine the relationship between monocyte subsets, the sCD163 monocyte activation marker, and neuropsychological performance among perinatally HIV-infected children initiating antiretroviral therapy (ART).

Methods: ART-naïve children from the PREDICT study were categorised into two groups: those on ART for ≥24 weeks (ART group, =201) and those untreated (no ART group, =79). This analysis used data from the baseline and week 144 including sCD163 and frequencies of activated monocytes (CD14+/CD16+/HLA-DR+), perivascular monocytes (CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+), and neuropsychological testing scores: Verbal and Performance Intelligence Quotient (VIQ and PIQ), Beery Visuomotor Integration (VMI) and Children's Color Trails 2 (CT2).

Results: Baseline demographic and HIV disease parameters were similar between groups. The median age was 6 years, CD4 was 20% (620 cells/mm), and HIV RNA was 4.8 log. By week 144, the ART the no ART group had significantly higher CD4 (938 552 cells/mm) and lower HIV RNA (1.6 4.38 log copies/mL, <0.05). sCD163 declined in the ART no ART group (median changes -2533 -159 ng/mL, <0.0001). Frequencies of all monocyte subsets declined in the treated but not the untreated group ( <0.05). Higher CD14+/CD16+/HLA-DR+ percentage was associated with higher VIQ, Beery VMI and CT2 scores. Higher percentages of CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+ were associated with higher CT2 and VIQ, respectively.

Conclusion: ART significantly reduced sCD163 levels and frequencies of activated and perivascular monocytes. Higher frequencies of these cells correlated with better neuropsychological performance suggesting a protective role of monocyte-macrophage immune activation in perinatal HIV infection in terms of neuropsychological function.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729380PMC
June 2015

A Population Pharmacokinetic/Pharmacodynamic Model Predicts Favorable HDL Cholesterol Changes Over the First 5 Years in Children Treated With Current Efavirenz-Based Regimens.

J Clin Pharmacol 2016 09 24;56(9):1076-83. Epub 2016 Feb 24.

Unité de Recherche Clinique Paris Centre, Assistance Publique Hôpitaux de Paris, France.

Efavirenz use is associated with changes in cholesterol concentrations, but it is unclear whether this effect is related to drug concentrations. Using efavirenz and cholesterol plasma concentrations measured in 87 antiretroviral-naive children in Thailand, we assessed indirect response models to describe the evolution of high- and low-density lipoprotein (HDL, LDL) cholesterol concentrations in relation to efavirenz plasma concentrations over time where efavirenz was assumed to either stimulate cholesterol production or inhibit its elimination. Simulations of cholesterol evolution for children with different average efavirenz concentrations (Cav ) according to their assumed status of "fast" or "slow" metabolizers of efavirenz were performed. At treatment initiation, children's median (interquartile range, IQR) age was 8 years (5 to 10), body mass index z-score 0.01 (-1.05 to 1.44), HDL 31 mg/dL (24 to 44), and LDL 83 mg/dL (69 to 100). Median (IQR) efavirenz Cav was 1.7 mg/L (1.3 to 2.1) during the period of observation. The best model describing the evolution of HDL and LDL cholesterol concentrations over time assumed that efavirenz inhibited their elimination. HDL concentrations increase over 5 years, whereas LDL concentrations increased only during the first 4 months and then returned to baseline levels afterward. Simulations predicted that, after 3 years, HDL would increase to 63 mg/dL in "fast" metabolizers and 97 mg/dL in "slow" metabolizers of efavirenz. The population pharmacokinetic-pharmacodynamic (PK-PD) model shows that favorable HDL cholesterol changes can be expected in children with current efavirenz dosing guidelines over 5 years of treatment.
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http://dx.doi.org/10.1002/jcph.701DOI Listing
September 2016

Premenstrual Disorders Among Perinatally HIV-Infected Adolescents.

J Acquir Immune Defic Syndr 2015 Dec;70(4):e150-3

*The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand †Department of Obstetrics and Gynecology, Chiangrai Prachanukroh Hospital, Chiangrai, Thailand ‡Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand §Department of Pediatrics, Phra Chomklao Hospital, Phetchaburi, Thailand ‖Department of Pediatrics, Phrapokklao Hospital, Chanthaburi, Thailand ¶The Thai Red Cross AIDS Research Centre, Bangkok, Thailand #SEARCH, Bangkok, Thailand **Currently, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD ††Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD ‡‡Department of Obstetrics and Gynecology, Phra Mongkut Klao Hospital, Bangkok, Thailand.

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http://dx.doi.org/10.1097/QAI.0000000000000762DOI Listing
December 2015

HLA-DRB1454 and predictors of new-onset asthma in HIV-infected Thai children.

Clin Immunol 2015 Mar 26;157(1):26-9. Epub 2014 Dec 26.

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand; SEARCH, Thai Red Cross AIDS Research Center, Bangkok, Thailand.

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http://dx.doi.org/10.1016/j.clim.2014.12.006DOI Listing
March 2015

Comparison of adherence monitoring tools and correlation to virologic failure in a pediatric HIV clinical trial.

AIDS Patient Care STDS 2014 Jun;28(6):296-302

1 HIV-NAT, Thai Red Cross AIDS Research Center , Bangkok, Thailand .

There is no consensus on a gold standard for monitoring adherence to antiretroviral therapy (ART). We compared different adherence monitoring tools in predicting virologic failure as part of a clinical trial. HIV-infected Thai and Cambodian children aged 1-12 years (N=207) were randomized to immediate-ART or deferred-ART until CD4% <15%. Virologic failure (VF) was defined as HIV-RNA >1000 copies/mL after ≥6 months of ART. Adherence monitoring tools were: (1) announced pill count, (2) PACTG adherence questionnaire (form completed by caregivers), and (3) child self-report (self-reporting from children or caregivers to direct questioning by investigators during the clinic visit) of any missed doses in the last 3 days and in the period since the last visit. The Kappa statistic was used to describe agreement between each tool. The median age at ART initiation was 7 years with median CD4% 17% and HIV-RNA 5.0 log(10)copies/mL and 92% received zidovudine/lamivudine/nevirapine. Over 144 weeks, 13% had VF. Mean adherence by announced pill count before VF in VF children was 92% compared to 98% in children without VF (p=0.03). Kappa statistics indicated slight to fair agreement between tools. In multivariate analysis adjusting for gender, treatment arm ethnicity and caregiver education, significant predictors of VF were poor adherence by announced pill count (OR 4.56; 95%CI 1.78-11.69), reporting any barrier to adherence in the PACTG adherence questionnaire (OR 7.08; 95%CI 2.42-20.73), and reporting a missed dose in the 24 weeks since the last HIV-RNA assessment (OR 8.64; 95%CI 1.96-38.04). In conclusion, we recommend the child self-report of any missed doses since last visit for use in HIV research and in routine care settings, because it is easy and quick to administer and a strong association with development of VF.
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http://dx.doi.org/10.1089/apc.2013.0276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046210PMC
June 2014

Association between lymphocyte and monocyte subsets and cognition in children with HIV.

AIDS Res Ther 2014 Jan 22;11(1). Epub 2014 Jan 22.

HIV-NAT, The Thai Red Cross AIDS Research Centre, 104 Rajdumri Road, Pathumwan, Bangkok 10330, Thailand.

Background: This study assesses the relationships between lymphocyte and monocyte subsets and intelligence quotient (IQ) scores in antiretroviral therapy (ART)-naive, HIV-infected Thai children without advanced HIV disease.

Findings: Sixty-seven ART-naive Thai children with CD4 between 15-24% underwent cognitive testing by Weschler intelligence scale and had 13 cell subsets performed by flow cytometry including naive, memory and activated subsets of CD4+ and CD8+ T cells, activated and perivascular monocytes and B cells. Regression modelling with log10 cell count and cell percentage transformation was performed.Median age (IQR) was 9 (7-10) years, 33% were male, CDC stages N:A:B were 1:67:31%, median CD4% and count (IQR) were 21 (18-24)%, 597 (424-801) cells/mm3 and HIV RNA (IQR) was 4.6 (4.1-4.9) log10 copies/ml. Most (82%) lived at home, 45% had a biological parent as their primary caregiver, and 26 (49%) had low family income. The mean (SD) scores were 75 (13) for full scale IQ (FIQ), 73 (12) for verbal IQ (VIQ) and 80 (14) for performance IQ (PIQ). Adjusted multivariate regression analysis showed significant negative associations between B cell counts and FIQ, VIQ and PIQ (p < 0.01 for all); similar associations were found for B cell percentages (p < 0.05 for all).

Conclusions: High B cell counts and percentages were strongly associated with poorer FIQ, VIQ and PIQ scores. Prospective, long-term assessment of cell subsets and determination of relevant B cell subpopulations could help further elucidate associations between lymphocyte subsets and neurocognitive development.
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http://dx.doi.org/10.1186/1742-6405-11-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900937PMC
January 2014

Impact of antiretroviral therapy on quality of life in HIV-infected Southeast Asian children in the PREDICT study.

AIDS Patient Care STDS 2013 Nov;27(11):596-603

1 HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center , Bangkok, Thailand .

Quality of life (QOL) is an important antiretroviral treatment (ART) outcome. We compared QOL among 299 Thai and Cambodian children ages 1-12 years-old, CD4 15-24% randomized to early (ART at week 0, N=149) versus deferred groups (ART when at CD4 <15%, N=150) and also compared with QOL data from age-matched healthy controls (N=275). Primary caregivers completed PACTG QOL questionnaires at week 0 and every 24 weeks until 144 weeks. Children were enrolled during March 2006 to September 2008. Mean (SD) age of children was 6.3 (2.8) years, 58% were female, 60% were Thai, %CDC N:A:B:C was 2:62:36:0%. During 144 weeks, all children in the early-group and 69 (46%) of deferred-group children started ART. There was no significant difference of QOL scores between treatment groups at baseline (all p>0.05) and at week 144 (all p>0.05). By multivariate analysis, the early-group had higher QOL score changes in five domains, including health perception (p=0.04), physical resilience (p=0.02), psychosocial well-being (p=0.04), social and role functioning (p<0.01), and symptoms (p=0.01) compared to the deferred group. QOL of HIV-infected children in both groups were lower than healthy control in all 7 domains at baseline (all p<0.05) and 5 of 7 domains at weeks 144 (p<0.01). In conclusion, no significant difference of QOL scores between treatment groups. Early ART commencement associated with greater increase of QOL scores over 144 weeks. QOL scores in HIV-infected children were lower than healthy controls.
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http://dx.doi.org/10.1089/apc.2013.0203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820144PMC
November 2013

Five-year trends in antiretroviral usage and drug costs in HIV-infected children in Thailand.

J Acquir Immune Defic Syndr 2013 Sep;64(1):95-102

Program for HIV Prevention and Treatment, Institut de Recherche pour le Développement IRD UMI 174-PHPT, France.

Background: As antiretroviral treatment (ART) programs mature, data on drug utilization and costs are needed to assess durability of treatments and inform program planning.

Methods: Children initiating ART were followed up in an observational cohort in Thailand. Treatment histories from 1999 to 2009 were reviewed. Treatment changes were categorized as: drug substitution (within class), switch across drug class (non nucleoside reverse-transcriptase inhibitors (NNRTI) to/from protease inhibitor (PI)), and to salvage therapy (dual PI or PI and NNRTI). Antiretroviral drug costs were calculated in 6-month cycles (US$ 2009 prices). Predictors of high drug cost including characteristics at start of ART (baseline), initial regimen, treatment change, and duration on ART were assessed using mixed-effects regression models.

Results: Five hundred seven children initiated ART with a median 54 (interquartile range, 36-72) months of follow-up. Fifty-two percent had a drug substitution, 21% switched across class, and 2% to salvage therapy. When allowing for drug substitution, 78% remained on their initial regimen. Mean drug cost increased from $251 to $428 per child per year in the first and fifth year of therapy, respectively. PI-based and salvage regimens accounted for 16% and 2% of treatments prescribed and 33% and 5% of total costs, respectively. Predictors of high cost include baseline age ≥ 8 years, non nevirapine-based initial regimen, switch across drug class, and to salvage regimen (P < 0.005).

Conclusions: At 5 years, 21% of children switched across drug class and 2% received salvage therapy. The mean drug cost increased by 70%. Access to affordable second- and third-line drugs is essential for the sustainability of treatment programs.
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http://dx.doi.org/10.1097/QAI.0b013e318298a309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744770PMC
September 2013

Cognitive function and neurodevelopmental outcomes in HIV-infected Children older than 1 year of age randomized to early versus deferred antiretroviral therapy: the PREDICT neurodevelopmental study.

Pediatr Infect Dis J 2013 May;32(5):501-8

HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early versus deferred ART in the Pediatric Randomized to Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) study. We now report neurodevelopmental outcomes.

Methods: Two hundred eighty-four HIV-infected Thai and Cambodian children aged 1-12 years with CD4 counts between 15% and 24% and no AIDS-defining illness were randomized to initiate ART at enrollment ("early," n = 139) or when CD4 count became <15% or a Centers for Disease Control (CDC) category C event developed ("deferred," n = 145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration, Purdue Pegboard, Color Trails and Child Behavioral Checklist. Thai children (n = 170) also completed Wechsler Intelligence Scale (intelligence quotient) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n = 319).

Results: At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% versus 24%, P < 0.001) and a greater percentage of children with viral suppression (91% versus 40%, P < 0.001). Neurodevelopmental scores did not differ by arm, and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on intelligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist.

Conclusions: In HIV-infected children surviving beyond 1 year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15%-24% versus <15%, but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.
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http://dx.doi.org/10.1097/INF.0b013e31827fb19dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664246PMC
May 2013

Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial.

Lancet Infect Dis 2012 Dec 9;12(12):933-41. Epub 2012 Oct 9.

HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand.

Background: The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival.

Methods: In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 1-12 years who were infected with HIV and had CD4 percentages of 15-24%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091.

Findings: Between March 28, 2006, and Sept 10, 2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 6·4 years (IQR 3·9-8·4). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (16-22%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 98·7% (95% CI 94·7-99·7; 148 of 150 patients) compared with 97·9% (93·7-99·3; 146 of 149 patients) in the early treatment group (p=0·6).

Interpretation: AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or future studies are needed to answer this clinical question.
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http://dx.doi.org/10.1016/S1473-3099(12)70242-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541427PMC
December 2012

Prevalence of human leukocyte antigen-B*5701 among HIV-infected children in Thailand and Cambodia: implications for abacavir use.

Pediatr Infect Dis J 2013 Mar;32(3):252-3

HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, The Thai Red Cross AIDS Research Center, Bangkok, Thailand.

Human leukocyte antigen (HLA)-B*5701 allele is associated with abacavir hypersensitivity. Limited data among Asians showed lower rates of HLA-B*5701 compared with Caucasians. In 296 children with HIV in Thailand and Cambodia, the prevalence of HLA-B*5701 was 4.0% (95% confidence interval: 1.6-8.0%) among Thai and 3.4% (95% confidence interval: 0.9-8.5%) among Cambodian children. HLA-B*5701 carriage is not uncommon among Thai and Cambodian children; it is close to the prevalence found in European and higher than the prevalence found in East Asian and African studies.
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http://dx.doi.org/10.1097/INF.0b013e3182745dbaDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955121PMC
March 2013

Prevalence of anemia and underlying iron status in naive antiretroviral therapy HIV-infected children with moderate immune suppression.

AIDS Res Hum Retroviruses 2012 Dec 25;28(12):1679-86. Epub 2012 Jul 25.

Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Anemia is common in HIV-infected children and iron deficiency is thought to be a common cause. This study investigates the prevalence of anemia, thalassemia, and underlying iron status in Thai and Cambodian children without advanced HIV disease to determine the necessity of routine iron supplementation. Antiretroviral (ARV)-naive HIV-infected Asian children aged 1-12 years, with CD4 15-24%, CDC A or B, and hemoglobin (Hb) ≥7.5 g/dl were eligible for the study. Iron studies, serum ferritin, Hb typing, and C-reactive protein were assessed. Anemia was defined as Hb <11.0 g/dl in children <5 years of age or <11.5 g/dl in children 5-12 years. We enrolled 299 children; 57.9% were female and the mean (SD) age was 6.3 (2.9) years. The mean (SD) CD4% and HIV-RNA were 20% (4.6) and 4.6 (0.6) log(10) copies/ml, respectively. The mean (SD) Hb and serum ferritin were 11.2 (1.1) g/dl and 78.3 (76.4) μg/liter, respectively. The overall iron deficiency anemia (IDA) prevalence was 2.7%. One hundred and forty-eight (50%) children had anemia, mostly of a mild degree. Of these, 69 (46.6%) had the thalassemia trait, 62 (41.8%) had anemia of chronic disease (ACD), 9 (6.1%) had thalassemia diseases, 3 (2.0%) had iron deficiency anemia, and 5 (3.4%) had IDA and the thalassemia trait. The thalassemia trait was not associated with increased serum ferritin levels. Mild anemia is common in ARV-naïve Thai and Cambodian children without advanced HIV. However, IDA prevalence is low; with the majority of cases caused by ACD. A routine prescription of iron supplement in anemic HIV-infected children without laboratory confirmation of IDA should be discouraged, especially in regions with a high prevalence of thalassemia and low prevalence of IDA.
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http://dx.doi.org/10.1089/AID.2011.0373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505043PMC
December 2012

Pharmacokinetics and safety of a new paediatric fixed-dose combination of zidovudine/lamivudine/nevirapine in HIV-infected children.

Antivir Ther 2011 ;16(8):1287-95

Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Alternatives to the available stavudine-containing paediatric fixed-dose combination (FDC) tablets are rapidly needed due to concerns regarding the cumulative toxicity of long-term stavudine exposure. We report the bioavailability and short-term safety of a novel paediatric FDC tablet of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP; 30/15/28 mg) in HIV-infected children.

Methods: In this Phase I/II open-label pharmacokinetic study, 42 children weighing 6-30 kg treated with NVP-based HAART for ≥4 weeks were randomized to receive the FDC tablets (GPO-VIR Z30) or the liquid formulations. Dosing was weight-based. Intensive 12-h blood sampling was performed after 2 weeks; subjects then crossed-over to the alternate formulation at equal doses and sampling repeated 2 weeks later. Pharmacokinetic parameters were determined by non-compartmental analysis. Buccal-swab samples were collected for cytochrome P450 (CYP)2B6 polymorphism analysis.

Results: With the FDC tablet, the geometric mean (90% CI) area under the curve (AUC) for ZDV, 3TC and NVP was 1.58 (1.49-1.68), 7.78 (7.38-8.19) and 68.88 (62.13-76.36) μg•h/ml, respectively. Rules for NVP therapeutic inadequacy were defined a priori, and despite lower NVP exposure with the tablet (P<0.001), the levels remained therapeutically adequate. ZDV AUC was similar between formulations. 3TC exposure was significantly higher with the tablet but comparable to historical data in adults and children taking branded tablets. While receiving the tablet, NVP AUC in children with CYP2B 516 GG (45%), GT (45%) and TT (10%) genotypes were 67.0, 74.5 and 106.4 μg•h/ml, respectively (P=0.04).

Conclusions: Disparities in drug exposure between formulations were observed; however, the FDC tablet delivered therapeutically adequate exposures of each drug and could well play an important role in simplifying antiretroviral treatment for children.
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http://dx.doi.org/10.3851/IMP1931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348490PMC
April 2012

Poor quality of life among untreated Thai and Cambodian children without severe HIV symptoms.

AIDS Care 2012 21;24(1):30-8. Epub 2011 Jul 21.

HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand.

There are limited data on quality of life (QOL) 1 in untreated HIV-infected children who do not have severe HIV symptoms. Moreover, such data do not exist for Asian children. Poor QOL could be a factor in deciding if antiretroviral therapy (ART) should be initiated. Thai and Cambodian children (n=294), aged 1-11 years, naïve to ART, with mild to moderate HIV symptoms and CD4 15-24% were enrolled. Their caregivers completed the Pediatric AIDS Clinical Trials Group QOL questionnaire prior to ART commencement. Six QOL domains were assessed using transformed scores that ranged from 0 to 100. Higher QOL scores indicated better health. Mean age was 6.1 (SD 2.8) years, mean CD4 was 723 (SD 369) cells/mm(3), 57% was female, and%CDC N:A:B was 2:63:35%. One-third knew their HIV diagnosis. Mean (SD) scores were 69.9 (17.6) for health perception, 64.5 (16.2) for physical resilience, 84.2 (15.6) for physical functioning, 77.9 (16.3) for psychosocial well-being, 74.7 (28.7) for social and role functioning, 90.0 (12.1) for health care utilization, and 87.4 (11.3) for symptoms domains. Children with CD4 counts above the 2008 World Health Organization (WHO) ART-initiation criteria (n=53) had higher scores in health perception and health care utilization than those with lower CD4 values. Younger children had poorer QOL than older children despite having similar mean CD4%. In conclusion, untreated Asian children without severe HIV symptoms had relatively low QOL scores compared to published reports in Western countries. Therapy initiation criteria by the WHO identified children with lower QOL scores to start ART; however, children who did not fit ART-initiation criteria and those who were younger also displayed poor QOL. QOL assessment should be considered in untreated children to inform decisions about when to initiate ART.
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http://dx.doi.org/10.1080/09540121.2011.592815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525829PMC
May 2012

CD4 cell count criteria to determine when to initiate antiretroviral therapy in human immunodeficiency virus-infected children.

Pediatr Infect Dis J 2010 Oct;29(10):966-8

Bamrasnaradura Infectious Disease Institute, Nonthaburi, Thailand.

We evaluated the validity of CD4 count against CD4% criteria of 2008 World Health Organization guideline for initiating antiretroviral therapy using the data of 446 human immunodeficiency virus-infected Asian children aged 1 to 12 years who were screened to the Pediatric Randomized of Early versus Deferred Initiation in Cambodia and Thailand study. The overall sensitivity and specificity were 34% and 98%, respectively. Using the current CD4 count criteria would globally result in 66% missed opportunity to initiate treatment in a timely fashion. Raising CD4 count thresholds should be considered to increase its sensitivity and reduce missed opportunity.
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http://dx.doi.org/10.1097/INF.0b013e3181e0554cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551976PMC
October 2010

Revisiting the role of neutralizing antibodies in mother-to-child transmission of HIV-1.

J Infect Dis 2006 Jun 21;193(11):1504-11. Epub 2006 Apr 21.

Universite Francois Rabelais, Equipe Associee 3856, Centre National de Reference du VIH, Tours, France.

We analyzed the association between mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) and maternal neutralizing antibodies to heterologous primary isolates of various HIV-1 clades, to test the hypothesis that protective antibodies are those with broad neutralizing activity. Our study sample included 90 Thai women for whom the timing of HIV-1 transmission (in utero or intrapartum) was known. The statistical analysis included a conditional logistic-regression model to control for both plasma viral load and duration of zidovudine prophylaxis. The higher the titer of neutralizing antibodies to a heterologous strain of the same clade, the lower the rate of MTCT of HIV-1. More specifically, high levels of neutralizing antibodies to the MBA (CRF01_AE) strain were associated with low intrapartum transmission of HIV-1. This suggested that such heterologous neutralizing antibodies may be involved in the natural prevention of late perinatal HIV transmission. These data are consistent with the hypothesis that the use of some antibodies might help to prevent perinatal HIV transmission, through passive immunoprophylaxis. Moreover, the study of humoral factors associated with MTCT of HIV-1 may identify correlates of protection that should help in the design of efficient HIV/acquired immunodeficiency syndrome vaccines.
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http://dx.doi.org/10.1086/503778DOI Listing
June 2006