Search

Currently migrant workers living with HIV (MWLHIV) in Thailand have access to antiretroviral treatment. We determined the frequency of depressive symptoms, HIV disclosure, and HIV-related stigma in this population. The cross-sectional study was conducted at 12 HIV clinics in community hospitals in Chiang Mai, Thailand. Data were collected from MWLHIV through face-to-face interviews. A 9-item Patient Health Questionnaire-9 (PHQ-9) and a Thai-validated HIV/AIDS stigma scales were used. A total of 316 MWLHIV participated; their median age was 39 years and 65% were female. Sixty (19%) had depressive symptoms, with higher frequency of depression in females (22.4% vs.12.6%, respectively

BackgroundSafe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed to select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar to those in adults, and was safe and well tolerated in young children.MethodsInternational Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is a phase 1-2 ongoing multicentre, open-label, non-comparative study of dolutegravir. A 5 mg dispersible tablet formulation of dolutegravir was studied in children aged 4 weeks to less than 6 years old, weighing at least 3 kg, with HIV RNA of greater than 1000 copies per mL and no previous treatment with integrase strand transfer inhibitor recruited from IMPAACT clinical research sites in Africa, the Americas, and Asia. Doses were selected on the basis of intensive pharmacokinetic evaluation on days 5-10, with safety and tolerability assessed up to 48 weeks. The primary objectives of this study are to evaluate the pharmacokinetics of dolutegravir in combination with optimised background therapy and to establish the dose of dolutegravir that achieves the targeted 24-h trough concentration and 24-h area under the curve for infants, children, and adolescents with HIV-1, to establish the safety and tolerability of dolutegravir at 24 and 48 weeks, and to select a dose that achieves similar exposure to the dolutegravir 50 mg once daily dose in adults. This analysis included participants treated with the proposed dose of dolutegravir dispersible tablets in two stages for each of three age cohorts. This trial is registered at ClinicalTrials.gov (NCT01302847) and is ongoing.FindingsWe recruited 181 participants from April 20, 2011, to Feb 19, 2020; of these, 96 received dolutegravir dispersible tablets. This analysis included 73 (35, 48% female) participants who received the final proposed dose with median (range) age of 1 year (0·1 to 6·0), weight (minimum-maximum) of 8·5 kg (3·7 to 18·5), plasma HIV-1 RNA concentration of 4·2 log10 copies per mL (2·1 to 7·0), and CD4% of 24·0% (0·3 to 49·0); 64 (87·7%) were treatment-experienced. The selected dose within each age cohort (≥2 years to

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

Objective: To determine the seroprevalence of antibodies against of diphtheria, tetanus, and pertussis among Thai adolescents. Methods: A cross-sectional study was conducted among Thai adolescents aged 11–20 years who had completed five doses of diphtheria, tetanus, and pertussis (DTP)-containing vaccine during childhood, either diphtheria toxoid, tetanus toxoid, whole-cell pertussis (DTwP) or diphtheria toxoid, tetanus toxoid, acellular pertussis (DTaP) vaccine. Protective antibodies against diphtheria, tetanus, and pertussis were defined as anti-diphtheria toxoid IgG ≥0.1 IU/ml, anti-tetanus toxoid IgG ≥0.1 IU/ml, and anti-Bordetella pertussis toxin IgG ≥5 IU/ml, respectively. Results: Of 220 adolescents (median age 16 years), 45% had received a tetanus toxoid, reduced diphtheria toxoid (Td) booster vaccine during adolescence, and none (0%) had received a tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) booster vaccine. Overall, 50%, 99%, and 57% of adolescents demonstrated protective antibodies against diphtheria, tetanus, and pertussis, respectively. The geometric mean concentrations (GMCs) of antibodies against diphtheria (p = 0.06) and tetanus (p < 0.001) were higher among adolescents who had received Td vaccine. Nevertheless, the antibody levels against both diseases waned over time, regardless of Td booster vaccination. Likewise, pertussis antibody levels gradually declined after the fifth childhood dose of DTwP/DTaP vaccine. Conclusions: Approximately half of these healthy Thai adolescents had not maintained protective antibodies against diphtheria and pertussis. A booster vaccination with diphtheria toxoid and/or acellular pertussis-containing vaccines is a crucial strategy to prevent such diseases in this population.

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.

Background The burden of HPV-related cancers in different regions worldwide varies according to several factors. This study aims to measure inequality in the risk of incidence of HPV-related cancers in term of geographical risk patterns in northern Thailand using a population-based cancer registry data. Methods Trends in age-standardized HPV-related cancer incidence were calculated for the 2008–2017 time period. The Besag-York-Molli´e model was used to explore the spatial distribution of the relative risk (RR) of HPV-related cancers at the district level. A higher RR reflects a larger disparity. The geographical risk pattern of the diseases in two periods, 2008–2012 and 2013–2017 were described and compared. Results From 2008 to 2017, the incidence of oropharyngeal and anal cancers showed a slightly increased trend in males but remained stable in females, the incidence of vulvar, vaginal and penile cancers were stable while the incidence of cervical cancer decreased. The RR range was closer to 1 in the second period compared to the first period. This suggests a decrease in the disparities of incidence of cervical cancer. However, in some areas near the Thai-Myanmar border, the RR values remained high. Conclusion The incidence rate of most HPV-related cancers remained low and stable over the study period in northern Thailand. For the most common HPV-related malignancy, cervical cancer, the incidence rate steadily decreased but with marked geographic disparities, possibly reflecting health inequity especially in the border areas.

With virologic suppression and longer life expectancy, older adults with HIV (OAHIV) are at risk for neurocognitive impairment (NCI). This study investigated neurocognitive performance, quality of life (QOL) and the association between OAHIV determinants.This cross-sectional study was conducted in OAHIV aged ≥ 50 years on antiretroviral treatment at community hospitals in Northern Thailand between September and November 2020. The Montreal Cognitive Assessment Thai Version (MoCA-T) and the Thai-validated Medical Outcomes Study HIV (MOS-HIV) were used. NCI was defined as MoCA-T scores25: 16-24 for amnestic mild cognitive impairment (aMCI) and16 for dementia. For QOL, higher scores meant better QOL; a physical health summary T-score ≥50 was defined as good QOL.Overall, 269 OAHIV were enrolled; 59% were female and 99% had virologic suppression. The current median age was 61.8 years (interquartile range [IQR] 58.9-65.7). The median duration of antiretroviral treatment was 10.5 years (IQR 8.5-13.5). The current median CD4 count (234 tested) was 484 cells/mmThe vast majority of OAHIV with virologic suppression had NCI. Approximately two-thirds had a mild impairment and one-fifth had dementia. Neurocognitive performance and QOL were not correlated. Addressing mild NCI would enable more targeted monitoring. Early intervention and support could minimize functional impairment with increased age.

The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the "Treat All" strategy.

Introduction To assess the burden of depression, anxiety and suicidality; and to determine the impact of integrated mental health and HIV services on treatment outcomes among Thai adolescents and young adults living with HIV (AYHIV). Methods A multicentre prospective cohort study was conducted among AYHIV (15 to 25 years), and age‐ and sex‐matched HIV‐uninfected adolescents and young adults (HUAY). The Patient Health Questionnaire 9‐item (PHQ‐9) and Generalized Anxiety Disorder 7‐item scales (GAD‐7) were used as screening tools for depressive and anxiety symptoms respectively. History of lifetime and recent suicidal ideations/attempts were ascertained. Elevated mental health screening scores were defined as having either significant depressive symptoms (PHQ‐9 ≥9), significant anxiety symptoms (GAD‐7 ≥10) or suicidality (lifetime; and recent [within two weeks]). Participants meeting these criteria were referred to psychiatrists for confirmatory diagnosis and mental health services. Follow‐up assessment with PHQ‐9 and GAD‐7 was performed one year after psychiatric referral. Results From February to April 2018, 150 AYHIV and 150 HUAY were enrolled, median age was 19.0 (IQR:16.8 to 21.8) years and 56% lived in urban areas. Among AYHIV, 73% had HIV RNA

The World Health Organization guidelines recommend that individuals living with HIV receive ≥ 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well-described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug interactions between isoniazid and efavirenz in pregnant women. Eight hundred forty-seven women received isoniazid for 28 weeks, either during pregnancy or at 12 weeks postpartum, and 786 women received efavirenz. After adjusting for NAT2 and CYP2B6 genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% in CYP2B6 normal metabolizers and 13% in slow and intermediate metabolizers. Overall, both isoniazid and efavirenz exposures were reduced during pregnancy, but the main determinants of drug concentration were NAT2 and CYP2B6 genotypes, which resulted in a five-fold difference for both drugs between rapid and slow metabolizers.

People living with HIV who are on antiretroviral treatment are at increased risk of developing premature cardiovascular disease. Children with perinatal HIV infection (PHIV) have survived through their adolescence and are entering adulthood. We determined the prevalence of metabolic syndrome, abnormal biochemical markers, and characterized body composition parameters in youth living with perinatal HIV infection. This cross-sectional study was conducted at the Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand from December 2017 to February 2018. PHIV-youths between 15

BACKGROUND: HIV-infected children with long-term nonprogressive disease (LTNPs) 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 two 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 to controls. Additionally, 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.

BackgroundThere is a growing body of evidence showing that early life events are associated with increased risk of cardiovascular and metabolic diseases later in adult life. However, there is a paucity of data in this field from Asian populations. In this study, we examined the association of birth order with obesity risk and cardiometabolic outcomes in young adults in Thailand.MethodsParticipants were the offspring from a birth cohort study in Chiang Mai (northern Thailand), who were followed up at ~20.5 years of age. Clinical assessments included anthropometry, blood pressure, fasting blood samples and carotid intima-media thickness. Insulin sensitivity was estimated using homeostatic model assessment of insulin resistance (HOMA-IR). Participants were stratified into two groups: first-borns and later-borns. Health outcomes between groups were compared using multivariable models adjusting for important confounders, in particular maternal body mass index (BMI).ResultsA total of 559 participants were studied: 316 first-borns (46% males) and 243 later-borns (47% males). Adjusted models showed anthropometric differences, with first-borns being 2.3 kg heavier (p=0.023) with a BMI 0.86 kg/m2 greater (p=0.019) than later-borns. Thus, rates of obesity were higher in first-borns than in later-borns (6.6% vs 2.9%), so that first-borns had an adjusted relative risk of obesity 3.3 times greater than later-borns [95% CI 1.42 to 7.88; p=0.006]. There were no observed differences in cardiovascular or metabolic parameters assessed, including HOMA-IR.ConclusionAs observed in other populations, first-borns in Thailand had greater BMI and an increased risk of obesity in young adulthood. However, we observed no other cardiometabolic differences between first- and later-borns.

Cardiovascular disease (CVD) is one among the leading causes of mortality in people living with HIV on antiretroviral treatment (ART) worldwide. We examined the prevalence of subclinical atherosclerosis, associated factors, and risk of CVD in older adults living with HIV (OALHIV). A cross-sectional study was conducted with patients aged ≥50 years with HIV infection receiving ART at community hospitals in Chiang Mai, Thailand. Age- and sex-matched patients without documented HIV infection who visited the general outpatient department were enrolled for comparison. Cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) were measured using the vascular screening system, VaSera System™ (Fukuda Denshi Co., Ltd., Japan) to determine subclinical atherosclerosis (defined as CAVI ≥9.0) and peripheral arterial disease (defined as ABI0.9), respectively. The Ramathibodi-Electric Generating Authority of Thailand (RAMA-EGAT) scores to predict the risk of coronary stenosis and the 10-year risk of ASCVD by pooled cohort equation were calculated. One hundred fifty-five patients were enrolled (107 HIV/48 comparison). The mean age was 59.0 years (SD 6.1); 67 (43%) were male. Participants in the HIV and comparison group were similar with respect to abnormal CAVI (57% vs. 58%

PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. METHODS: Regional Asian data (2001–2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count

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.

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

To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10-25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6-19.2) years and 10.5 (7.1-12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8-18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (≥2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7-511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1-289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.

BackgroundDisclosure of HIV status is a critical gateway to HIV prevention. Despite many studies on this topic, there is a gap in knowledge regarding HIV status disclosure and risky sexual behavior in HIV-infected female migrant workers. The current study addressed this research gap, and focused on HIV-infected Shan female migrant workers in Northern Thailand.MethodsThis study conducted in-depth interviews with 18 HIV-infected Shan female migrants (aged between 23-54 years old) and 29 healthcare workers in district hospitals in Chiang Mai. Content analysis was employed to identify particular themes related to HIV status disclosure, sexual risk behavior, and ART adherence.ResultsWe found that non-disclosure to husbands/partners was mostly related to fear of marital conflict and of losing social and financial support. Non-disclosure prevented Shan female migrant workers from negotiating condom use with their partners. Reasons for not disclosing to friends, family and other community members were mostly related to feared rejection and discrimination due to HIV-related stigma. Accounts of condomless sex in the context of HIV status disclosure suggest that gender norms and male dominance over women influenced decision-making for safe sex. Lastly, some female migrant workers perceived low risk of HIV transmission with good adherence to the ART.ConclusionsThis study highlighted the complex challenges of HIV status disclosure among HIV-positive Shan female migrant workers and the link between disclosure/non-disclosure and condom use. There is a pressing need to create realistic disclosure mechanisms that take into account the socio-cultural barriers to disclosure including marital conflicts, stigma, and gender norms. Messages to encourage condom use should be delivered carefully so that knowledge of the HIV transmission reduction qualities of good ART adherence does not serve as a barrier to condom use.

Alterations in subcortical brain structures have been reported in adults with HIV and, to a lesser extent, pediatric cohorts. The extent of longitudinal structural abnormalities in children with perinatal HIV infection (PaHIV) remains unclear. We modeled subcortical morphometry from whole brain structural magnetic resonance imaging (1.5 T) scans of 43 Thai children with PaHIV (baseline age = 11.09±2.36 years) and 50 HIV− children (11.26±2.80 years) using volumetric and surface-based shape analyses. The PaHIV sample were randomized to initiate combination antiretroviral treatment (cART) when CD4 counts were 15–24% (immediate: n = 22) or when CD4

We analyzed final height of 273 perinatally HIV-infected Asian adolescents older than 18 years at their last clinic visit. By the World Health Organization child growth reference, 30% were stunted, but by the Thai child growth reference, 19% were stunted. Half of those who were stunted at antiretroviral therapy initiation remained stunted over time. Being male and having a low baseline height-for-age Z score of less than -1.0 were associated with low final height Z score.

BACKGROUND: Hepatitis B (HBV)-HIV coinfection is associated with liver inflammation, which can progress to liver fibrosis/cirrhosis and hepatocellular carcinoma. We determined HBV seroprevalence in children and adolescents participating in the TREAT Asia Pediatric HIV Observational Database. METHODS: A multi-site cross-sectional study was conducted in HIV-infected patients currently aged

OBJECTIVES HIV infection has become a chronic disease requiring long-term treatment. Premature cardiovascular disease resulting from atherosclerosis in the HIV-infected population has been observed. We assessed the prevalence of peripheral artery disease (PAD), a common consequence of atherosclerosis, in HIV-infected patients aged ≥ 50 years receiving antiretroviral treatment (ART). METHODS This cross-sectional study was conducted in 12 community hospitals in Chiang Mai, Thailand. Inclusion criteria were as follows: (1) age ≥ 50 years, (2) positive HIV status, and (3) currently receiving ART. Age- and sex-matched hospital patients without documented HIV infection were enrolled as a comparison group. Clinical data were extracted from hospital records. Personal information and details of PAD-related symptoms were obtained through face-to-face interviews. The diagnosis of PAD was made using ankle-brachial index (ABI) measurement. RESULTS Seven hundred and twenty-four participants were enrolled in the study (362 HIV-infected patients and 362 patients in the comparison group). In the HIV-infected group, 43% were male; the mean (± standard deviation) age was 57.8 ± 5.6 years. The mean (± standard deviation) times from HIV diagnosis and ART initiation were 10.0 ± 4.3 and 8.6 ± 3.5 years, respectively. The prevalence of abnormal ABI (

In 188 HIV-infected children receiving efavirenz, a lower mid-dose (C-12) was associated with a higher risk of HIV-1 viral load >400 copies/mL (P = 0.03). Simulations for a normalized population receiving US Food and Drug Administration weight-band dosing predicted that 15% of children would have a C-12 below target threshold (

Copyright © 2015 Wolters Kluwer Health, Inc. Background: Perinatal use of combination antiretroviral therapy dramatically reduces vertical (mother-to-child) transmission of HIV but has led to a growing population of children with perinatal HIV-exposure but uninfected (HEU). HIV can cause neurological injury among children born with infection, but the neuroanatomical and developmental effects in HEU children are poorly understood. Methods: We used structural magnetic resonance imaging with diffusion tensor imaging to compare brain anatomy between 30 HEU and 33 age-matched HIV-unexposed and uninfected (HUU) children from Thailand. Maps of brain volume and microstructural anatomy were compared across groups; associations were tested between neuroimaging measures and concurrent neuropsychological test performance. Results: Mean (standard deviation) age of children was 10.3 (2.8) years, and 58% were male. All were enrolled in school and lived with family members. Intelligence quotient (IQ) did not differ between groups. Caretaker education levels did not differ, but income was higher for HUU (P < 0.001). We did not detect group differences in brain volume or diffusion tensor imaging metrics, after controlling for sociodemographic factors. The mean (95% confidence interval) fractional anisotropy in the corpus callosum was 0.375 (0.368-0.381) in HEU compared with 0.370 (0.364-0.375) in HUU. Higher fractional anisotropy and lower mean diffusivity were each associated with higher IQ scores in analyses with both groups combined. Conclusions: No differences in neuroanatomical or brain integrity measures were detectable in HEU children compared with age-matched and sex-matched controls (HUU children). Expected associations between brain integrity measures and IQ scores were identified suggesting sufficient power to detect subtle associations that were present.

Unlike well-studied antibody responses to pandemic 2009 H1N1 influenza A virus vaccines in human immunodeficiency virus-infected (HIV+) individuals, less well understood are cell-mediated immune (CMI) responses to this antigen in this susceptible population. We investigated such influenza-specific CMI responses in 61 HIV+ individuals and in 20 HIV-negative (HIV-) healthy controls. Each was vaccinated with a single licensed dose of inactivated, split-virion vaccine comprised of the influenza A/California/7/2009 (H1N1) virus-like strain. Cells collected just prior to vaccination and at 1 and 3 months afterwards were stimulated in vitro with dialyzed vaccine antigen and assayed by flow cytometry for cytokines TNF-α, IFN-γ, IL-2, and IL-10, for degranulation marker CD107a, as well as phenotypes of memory T-cell subpopulations. Comparable increases of cytokine-producing and CD107a-expressing T cells were observed in both HIV+ subjects and healthy HIV-controls. However, by 3 months post-vaccination, in vitro antigen stimulation of peripheral blood mononuclear cells induced greater expansion in controls of both CD4 and CD8 central memory and effector memory T cells, as well as higher expression of the activation marker CD69 and chemokine receptors CCR5 and CXCR3 than in HIV+ subjects. We concluded CD4+ and CD8+ memory T cells produce cytokines at comparable levels in both groups, whereas the expression after in vitro stimulation of molecules critical for cell migration to infection sites are lower in the HIV+ than in comparable controls. Further immunization strategies against influenza are needed to improve the CMI responses in people living with HIV.

BACKGROUND: Children with vertically acquired human immunodeficiency virus (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 (ART) 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 ART for a median of 34 months (range: 33–42) with HIV RNA

Background: Hepatitis B virus (HBV) and HIV coinfection is associated with risk of progression to chronic liver disease. We assessed liver stiffness in HBV-HIV coinfected youths. Methods: A cross-sectional study in HBV-HIV coinfected youths aged 18 to 25 years who received a tenofovir (TDF)-containing antiretroviral therapy regimen for >96 weeks. Measurements included HBV DNA level, HBV serology profiles, and transient elastography (TE). The cutoff for TE results included ≥5.9 kPa for F2-moderate fibrosis, ≥7.4 kPa for F3-severe fibrosis, and ≥9.6 kPa for F4-cirrhosis. Results: From March to December 2016, 15 HBV-HIV coinfected youths with a median duration on TDF-containing regimens of 3.3 years were enrolled. Five (33%) youths had significant liver fibrosis, 3 with F2-moderate, 1 with F3-advanced fibrosis, and 1 with F4-cirrhosis. Other 5 without liver fibrosis had hepatitis B surface e antigen (HBsAg) and hepatitis B surface e antigen (HBeAg) loss. Higher mean alanine transaminase (ALT) was observed among the group with F2-F4 when compared to those with F0. Conclusion: Liver fibrosis was evidenced in HBV-HIV coinfected youths in Thailand. Transient elastography might be considered for those who do not achieve HBsAg loss or have persistent ALT elevation while on treatment.

BACKGROUND The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged

Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate- to high-level LPV resistance in Asian children.LPV concentration, HIV RNA level, and adherence data from study participants in Thailand, Vietnam, and Indonesia receiving second-line LPV-based ART and followed for ≥24 weeks were analyzed.A total of 223 children at a median age of 10.4 (interquartile range, 7.9-13.4) years were enrolled, and 61% of them were male. Their mean CD4 was 842 ± 438 cells per cubic millimeter, and the median LPV duration was 2.5 (interquartile range, 1.3-4.2) years. Five of 84 (6%) and 18 of 139 (13%) children had LPV trough and random concentrations1.0 mg/L at study week 24. Using either of these trough or random LPV concentrations, a cutoff at 1.0 mg/L gave an area under the receiver operating characteristics curve of 0.69 in predicting VF with sensitivity of 44% (95% CI 23-66) and specificity of 94% (95% CI 89-97). Seven of 21 with VF and resistance results available had ≥1 major protease inhibitor mutation. Multivariate logistic regression found LPV concentrations1.0 mg/L (odds ratio, 6.47; 95% CI 2.15-19.50, P = 0.001) and CD4 ≤20% (odds ratio, 2.83; 95% CI 1.01-7.89, P = 0.05) were independently associated with HIV RNA1000 copies per milliliter. No factors predicted major LPV resistance mutations.The authors support that the DHHS target LPV concentration of1.0 mg/L is predictive of VF, but not of the presence of major LPV mutations.

Background This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents. Methods This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10–18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated. Results Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7–17.4) years and TDF treatment duration (IQR) was 2.3 (1.4– 3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6–16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 ( P=0.27), and -0.3 and -0.2 ( P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD Conclusions Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.

Purpose To assess the incidence and predictors of postsuppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy in Asia. Methods Perinatally HIV-infected Asian adolescents (10–19 years) with documented virologic suppression (two consecutive viral loads [VLs] 1,000 copies/mL). Results Of 1,379 eligible adolescents, 47% were males. At baseline, 22% were receiving protease inhibitor–containing regimens; median CD4 cell count (interquartile range [IQR]) was 685 (448–937) cells/mm 3 ; 2% had preadolescent virologic failure (VF) before subsequent suppression. During adolescence, 180 individuals (13%) experienced postsuppression VR at a rate of 3.4 (95% confidence interval: 2.9–3.9) per 100 person-years, which was consistent over time. Median time to VR during adolescence (IQR) was 3.3 (2.1–4.8) years. Wasting (weight-for-age z-score 3 , and 4.1 (3.5–4.7) log 10 copies/mL, respectively. Conclusions A modest and consistent incidence of postsuppression VR was documented during adolescence in our cohort. Having poor weight, receiving second-line regimens, and prior VF were associated with an increased VR rate. Adolescents at higher risk of VR may benefit from more intensive VL monitoring to enhance adherence management.

Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population.Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4%25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification.Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity.Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.

Low vitamin D level is associated with adverse health outcomes and compromises HIV treatment response. We assess vitamin D status in HIV-infected Thai children receiving combination antiretroviral therapy (cART).A cross-sectional study in perinatally HIV-infected children. Vitamin D deficiency and vitamin D insufficiency were defined as serum 25-hydroxyvitamin D (25-OHD) level Eighty participants were enrolled. Their median age was 12.2 years. The median CD4 lymphocyte count was 784 cell/mm3; 95% had HIV RNA Most of perinatally HIV-infected children receiving cART had low vitamin D level. Calcium and vitamin D supplement might be beneficial.

Background: Single nucleotide polymorphism of the hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene is a cause of variation in plasma efavirenz (EFV) concentrations. We aimed to determine the allelic distribution of CYP2B6 gene, plasma levels of EFV, the prevalence of clinical depression, and their correlations in northern Thai population. Methods: This was a cross-sectional study of HIV-infected patients on EFV-containing antiretroviral regimens for ≥48 weeks. A single blood specimen was collected for determination of the mid-dose plasma EFV concentration and CYP2B6- 516G>T polymorphism. The presence and severity of depression were assessed. Results: One hundred patients were enrolled [mean age (± SD) was 41.81 ± 8.44 years, mean CD4 lymphocyte count 462 ± 193 cells/ul]. The genotype CYP2B6-516 guanine/guanine (G/G), guanine/thymidine (G/T), and T/T were found in 49%, 37%, and 14% of patients, respectively. The allele frequency of CYP2B6-516 G to T replacement was 32.5%. The median plasma EFV concentration was 2,616 ng/mL (IQR 1,851-3,742); 79% had EFV plasma concentrations from 1,000 to 4,000 ng/mL. The mean EFV concentrations for those with G/G, G/T and T/T genotypes were 2,082±630, 3,166±1,074, and 11,196±6,265 ng/mL, respectively (p T polymorphism was the only factor associated with high plasma EFV levels. Nineteen patients had depression; 13 of 18 (72%) with mild and one with major depression had normal plasma EFV level. A weak correlation between plasma EFV concentrations and depression scores was observed (p=0.009, R2=0.059). Conclusions: The prevalence of CYP2B6-516G>T polymorphism in northern Thai population is high and strongly associated with inter-individual drug levels variation.

Substitution of stavudine with zidovudine may lead to recovery from lipodystrophy (LD) in HIV-infected children.We prospectively followed HIV-infected children enrolled in an earlier LD study conducted between 2002 and 2004 at Chiang Mai University Hospital in northern Thailand. In 2006, stavudine was substituted with zidovudine. All children were evaluated by a clinical LD checklist modified from that of the European Pediatric LD study group together with waist/hip measurement at baseline and 24, 48, 72, and 96 weeks after substitution. The waist-to-hip ratios were converted to age- and sex-adjusted z scores based on normal ranges in healthy Thai children.Forty-five lipodystrophic children with 36 episodes of lipohypertrophy and 22 episodes of lipoatrophy were enrolled. By weeks 48 and 96 after substitution, 40% and 47% of lipohypertrophy resolved, whereas 59% and 73% of lipoatrophy resolved, respectively. The rate of resolution of lipoatrophy was higher than that of lipohypertrophy at 48 weeks after substitution and thereafter. Ninety-six weeks after changing to zidovudine therapy, 8 children still had LD (1 with both lipoatrophy and lipohypertrophy, 7 with lipohypertrophy). No clinically significant hematologic adverse event was observed.Substitution of stavudine with zidovudine resulted in decreased severity or resolution of LD among HIV-infected children and adolescents.

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 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.

To evaluate the immunogenicity and safety of the monovalent pandemic influenza A (H1N1) 2009 (pH1N1) vaccine in HIV-infected Thai children, 2 doses, 28days apart, of non-adjuvant monovalent pH1N1 vaccine (Panenza(®) by Sanofi Pasteur, 15μg/dose) provided by the National Health Promotion Program of the Thai Ministry of Public Health were given to HIV-infected children. Immunogenicity was measured by hemagglutination inhibition test (HAI) using two antigens, pH1N1 (A/Thailand/104/09) and seasonal influenza A H1N1 (A/Brisbane/59/07-like), at baseline, and 28days after each dose. Serologic response was defined as four-fold rising of HAI titer or HAI titer ≥1:40 for those with baseline titer ≤1:10. Adverse events were recorded for 7days after each vaccination. Of the 119 HIV-infected children enrolled, 60 (50.4%) were female with a median (IQR) age of 10.4 (7.2-13.7)years. All but 2 (98.3%) children were receiving antiretroviral therapy. At baseline, the median CD4 cell count was 782 (570-1149)cells/mm(3), 91 (80.5%) children had HIV RNA level

BACKGROUND: Combination antiretroviral therapy (ART) has been used for HIV-infected children in many Asian countries since 2002. This study describes survival outcomes among HIV-infected children in a multicenter regional cohort in Asia. PATIENTS AND METHODS: Retrospective and prospective data collected through March 2009 from children in 5 countries enrolled in TREAT Asias Pediatric HIV Observational Database were analysed. Multivariate Cox proportional hazard models were used to assess factors associated with mortality in children who received ART. RESULTS: Among 2280 children 1752 (77%) had received ART. During a median follow-up of 3.1 years after ART 115 (6.6%) deaths occurred giving a crude mortality rate of 1.9 per 100 child-years [95% confidence interval (CI): 1.6 to 2.4]. The mortality rate was highest in the first 3 months of ART (10.2 per 100 child-years; 95% CI: 7.5 to 13.7) and declined after 12 months (0.9 per 100 child-years; 95% CI: 0.7 to 1.3). Those with a low recent CD4 percentage who started ART with lower baseline weight-for-age Z score or with WHO clinical stage 4 had an increased risk of death. Of 528 (23%) children who never received ART 36 (6.8%) died after presenting to care giving a crude mortality rate of 4.1 per 100 child-years (95% CI: 3.0 to 5.7) with a lost-to-program rate of 31.5 per 100 child-years (95% CI: 28.0 to 35.5). CONCLUSIONS: The high mortality during the first 3 months of ART and in those with low CD4 percentage support the implementation of early diagnosis and ART initiation.

Three years after measles, mumps, and rubella revaccination in 38 human immunodeficiency virus-infected children who had achieved immune recovery after antiretroviral therapy, the prevalence of protective antibody levels was 85% for measles, 61% for mumps, and 79% for rubella, compared with 88%, 84%, and 100%, respectively, 1 month after revaccination.

This study aimed to assess family functioning in adolescents with perinatal HIV infection receiving antiretroviral therapy compared with healthy controls. Correlations between self-reported and caregiver-reported family functions were also evaluated. A sample of 195 participants including 65 perinatally HIV-infected adolescents and 130 healthy controls were enrolled. The total family functioning score in HIV-infected adolescents was significantly lower than that in healthy controls by self-report (105.86 vs 115.41; P ≤ .001). Caregivers of HIV-infected adolescents also reported lower scores of family functioning than those of controls (109.91 vs 114.98; P ≤ .001). Among the HIV-infected group, there was no or minimal correlation between the self-reported and caregiver-reported total scores of family functioning. However, there were moderate correlations between self-reported and caregiver-reported family functioning total scores in the control group. Overall, HIV-infected adolescents reported lower family functioning than healthy controls. Improved functioning in the family may help with better adjustment in perinatally HIV-infected adolescents.

Growth failure is a common problem in HIV-infected children. The extent to which this growth failure could be reversed after the children receive antiretroviral therapy (ART) is not known. This study assessed the incidence of growth failure in HIV-infected Thai children, impact of ART on growth, and the predictors of growth reversal after initiating ART. Growth parameters and other characteristics were extracted from the database of a prospective cohort of HIV-infected children (ageor=15 years) who were enrolled to initiate non-nucleoside reverse transcriptase inhibitor-based ART between August 2002 and May 2007. Body weight and height measurements, CD4 cell counts, plasma HIV RNA levels were collected at baseline and 24-week intervals. A total of 225 HIV-infected children were included, 116 (51%) were males. The median age at baseline was 7.4 years (interquartile range [IQR] 5.2-9.8). Fifty-three percent were in Centers for Disease Control and Prevention (CDC) category C and 54% had CD4 percentage 5 or less. The mean (standard deviation [SD]) of baseline weight-for-age (WAZ) and height-for-age (HAZ) z-scores were -2.02 (1.17) and -2.22 (1.51). The median follow-up time was 216 weeks (IQR 120-240). The cumulative probability of growth reversal among the 179 subjects with growth failure at entry was 58% (95% confidence interval [CI] 49-67) at week 240. In a multivariate Cox regression model, higher entry WAZ (p0.001) and HAZ (p0.001), use of a nevirapine-based regimen (compared to efavirenz, p = 0.027) and larger CD4% gains to week 48 (p0.001) were significant predictors of growth reversal after initiating ART. NNRTI-based ART leads to a substantial improvement in growth of HIV-infected children. Initiation of ART before the children developed growth failure should be encouraged.

Background Highly active antiretroviral therapy (HAART) is reported to cause insulin resistance among adults, but effects on children are less clear. We attempted to describe the prevalence of insulin resistance among HIV-infected children receiving HAART. Methods Insulin resistance was assessed at 96 weeks of treatment with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based HAART (nevirapine or efavirenz with stavudine and lamivudine) among children in Chiang Mai, Thailand. Insulin resistance was defined as homeostasis model assessment for insulin resistance (HOMA-IR) ≥3.16, fasting c-peptide ≥4.40 ng/mL or fasting insulin ≥25.0 μU/mL. Impaired fasting glucose (IFG) was defined as glucose ≥110 mg/dL. Measurements were analysed for associations with age, lipodystrophy, treatment regimen and clinical data. Results The prevalence of insulin resistance was 6.5%; no child had IFG. Those with insulin resistance were older with higher body mass index. Children ≥10 years had higher HOMA-IR, c-peptide and insulin, but no difference was seen in the frequency of insulin resistance. No associations between insulin resistance and lipodystrophy or treatment regimen were detected. Conclusions Insulin resistance is uncommon among children receiving NNRTI-based HAART and is unrelated to lipodystrophy.

Department of Pediatrics, Faculty of Medicine, Chiang Mai University,Chiang Mai, ThailandObjectiveIn resource-limited countries, stavudine (d4T) is commonly used as part of the initial highly activeantiretroviral therapy (HAART) regimen. Many patients who subsequently develop lipodystrophyswitch from d4T to zidovudine (ZDV), a drug that can be myelotoxic. We aimed to study thespectrum and severity of haematological changes following this substitution.MethodsThis was a retrospective cohort study. The inclusion criteria were as follows: HIV-infected childrenwere included who (1) were 2–15 years old at the time of HAART initiation, (2) had not beendiagnosed as having haematological diseases, (3) had been receiving a first HAART regimenconsisting of either nevirapine or efavirenz, together with lamivudine and d4T, for at least 48 weeksand (4) had switched from d4T to ZDV at least 48 weeks previously.ResultsSeventy-eight children were included in the study. Thirty-six (46%) were male. The mean age was10.3 years (standard deviation 3.1 years). The switch had been made a median time of 65 weeks(range 48–97 weeks) previously. There was no significant change in CD4 lymphocyte count orpercentage, or HIV RNA level, after the switch. There was a statistically significant decrease inhaemoglobin level (12.6 vs.12.1g/dL; Po0.001), total white blood cell (WBC) count (8088 vs.6910cells/mL; Po0.001) and absolute neutrophil count (ANC) (4320 vs. 3448cells/mL; Po0.001).However, the decreases never reached Division of AIDS grade 3 or 4 severity, and none of thepatients had clinical symptoms or signs of anaemia, leukopenia, or neutropenia. No participant hadto discontinue ZDV during the 48-week follow-up period.ConclusionIn a paediatric population, statistically significant decreases in haemoglobin level, WBC count andANC occurred following the substitution of d4T with ZDV, but the magnitudes of the decreases weresmall and not clinically significant.Keywords: anaemia, children, HIV, stavudine, zidovudineReceived: 31 October 2007, accepted 22 January 2008

The low prevalence of measles antibody in human immunodeficiency virus (HIV)-infected children after immune recovery as a result of highly active antiretroviral therapy increases the risk of morbidity and mortality from disease. The objective of our study was to evaluate the efficacy and safety of revaccination with measles, mumps, and rubella (MMR) vaccine in HIV-infected children with immune recovery.Inclusion criteria were (1) HIV-infected children aged5 years, (2) a nadir CD4 lymphocyte percentageor=15%, (3) immune recovery (defined as a CD4 lymphocyte percentage15% foror=3 months after highly active antiretroviral therapy), and (4) no protective antibody against measles. Each child received 1 dose of MMR vaccine, and antibodies were measured at 4 and 24 weeks after vaccination. Protective antibodies were defined as an antimeasles immunoglobulin G (IgG) levelor=320 mIU/mL, an antimumps IgG titer1:500, and an antirubella IgG level10 IU/mL.There were 51 participants. The mean age (+/- standard deviation) was 10.2 +/- 2.5 years. Prior to revaccination, 28 participants (55%) had baseline protective antibody to mumps, and 11 (20%) had baseline protective antibody to rubella. The prevalence of protective antibody at 4 weeks was 90%, 100%, and 78% for measles, rubella, and mumps, respectively, and then slightly decreased to 80%, 94%, and 61%, respectively, at 24 weeks after revaccination. No serious adverse reactions were attributed to revaccination.The majority of HIV-infected children with immune recovery can develop protective antibodies after MMR revaccination. Revaccination with MMR vaccine in HIV-infected children with immune recovery should be considered to ensure individual immunity and limit the spread of disease.

Despite a history of hepatitis B virus (HBV) vaccination prior to highly active antiretroviral therapy (HAART), most of HIV-infected children do not have protective antibody to HBV infection. The efficacy of an additional booster dose in children with immune recovery on HAART remains unknown. This study was conducted to determine the response rate of HBV antibody after re-vaccination in HIV-infected children with immune recovery on HAART. Sixty-three successfully HAART-treated HIV-infected children with history of prior HBV vaccination received 10microg doses of recombinant HBV vaccine (Government Pharmaceutical Organization-Merieux Biological Product, Bangkok, Thailand) intramuscularly at 0, 2 and 6 months. The vaccine response rates were 17.4, 82.5, and 92.1% at 2, 6 and 7 months after the first dose of vaccine, respectively. Plasma HIV RNA level below the limit of detection at the time of re-vaccination was associated with successful vaccine response. HIV-infected children with immune recovery after HAART are likely to benefit from three-dose HBV re-vaccination.

Pediatric antiretroviral therapy programs have recently been implemented in resource-limited settings. Their impact in a prospective cohort is not well documented. The aim of this study was to evaluate the rates and causes of hospitalization and mortality among human immunodeficiency virus (HIV)-infected Thai children after receiving highly active antiretroviral therapy (HAART).Children who started receiving HAART from August 2002 to March 2005 were prospectively observed. The patients included in the study were antiretroviral-naive HIV-infected children who had CD4 cell percentagesor =15% before treatment. All patients were observed for at least 48 weeks.One hundred ninety-two children were included. The mean age at HAART initiation was 7.6 years (range, 0.4-14.8 years). At baseline, the mean CD4 cell percentage (+/-SD) was 5.2%+/-4.9%, and the mean plasma HIV RNA level (+/-SD) was 5.4+/-0.5 log(10) copies/mL. Sixty-seven children (35%) were hospitalized a total of 108 times. The hospitalization rate decreased from 30.7% during the first 24-week period to 2.0% during weeks 120-144 after initiation of HAART. Fifty-nine hospital admissions (54.6%) occurred during the first 24 weeks of HAART. Causes of hospitalization were pneumonia and other bacterial infections (61.7%), immune reconstitution syndrome (23.4%), noninfectious illness (6.5%), opportunistic infection (5.6%), and drug-related events (2.8%). The mortality rate decreased from 5.7% in the first 24 weeks to 0%-0.6% in the subsequent 24-week intervals.Hospitalization and mortality rates significantly decreased among HIV-infected children receiving HAART. Most hospitalizations and deaths occurred during the first 24 weeks of HAART.

Background The National Access to Antiretroviral Program for People Living with HIV/AIDS was launched in Thailand in 2002. HIV-infected, antiretroviral-naive, severely immunosuppressed children were initiated on highly active combination antiretroviral treatment (cART). This study aimed to determine the long-term effectiveness of cART. Methods Data were extracted from medical records. Primary end points were mortality rate, proportion of children who remained on first-line cART regimen and children with plasma HIV RNA level (pVL) Results From August 2002 to July 2003, 107 children were enrolled. The baseline median age was 7.6 years (IQR 5.7–10.0), the median CD4+ T-cell count was 60 cells/mm3 (IQR 21–272) and the median pVL was 5.37 log10 copies/ml (IQR 5.01–5.76). The mortality rate during and after the first year was 3.7 and 0.006 deaths/100 person-years, respectively. At week 520, 90 (84%) continued to be actively followed. Their median age was 17.8 years (IQR 15.8-19.8). 73 (81% as-treated) remained on the first-line regimen, while 18 (20%) had switched to a second-line cART regimen, at the median time of 272 weeks (IQR 256-363) after the first-line cART initiation. 69 (77%) had pVL+ T-cell count was 636 cells/mm3 (IQR 466-804). 83 (92%) and 64 (71%) had CD4+ T-cell counts ≥200 and >500 cells/mm3, respectively. Conclusions Long-term virological control, favourable immunological outcomes and healthy survival was achieved in severely immunosuppressed, perinatally HIV-infected children who started first-line NNRTI-based cART. Continuing surveillance for long-term complications is warranted.

We determined the prevalence and incidence of liver dysfunction before and after initiation of combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database.Data from children initiated on cART between 2 and 18 years of age with baseline alanine aminotransferase (ALT) available before and at least once after cART initiation in TREAT Asia Pediatric HIV Observational Database between 2008 and 2012 were analyzed. Prevalence and incidence of liver dysfunction and biomarkers including the aspartate aminotransferase to platelet ratio index and FIB4 index (a noninvasive panel to stage liver disease) were assessed.Data from 1930 children were included. Their median age was 6.9 years; 49% were male; 98% were perinatally infected and 94% were initiated on non-nucleoside reverse transcriptase-based cART regimens. Before cART, the prevalence of ALT ≥3 times the upper limit of normal (×ULN) was 5.8%. There were 8.5% of children with aspartate aminotransferase to platelet ratio index1.5 (suggestive of liver fibrosis) and 2.7% with FIB4 index1.3 (predictive of possible cirrhosis). Among the 1143 cases with normal baseline ALT (≤1×ULN), the incidence of ALT 3×ULN after cART was 1.19 of 1000 person-months (95% confidence interval: 0.93-1.51). Two of 350 with available tests (0.6%) met Hy's law (ALT3×ULN and total bilirubin2×ULN). By multivariate analysis, baseline hemoglobin7.5 g/dL was a predictor of ALT3×ULN, whereas age 5-9 years at cART initiation was protective for liver dysfunction.We demonstrated a low prevalence and incidence of liver dysfunction before and after cART initiation in children with normal baseline chemistries. In this population facing life-long cART, prospective surveillance for emergence of liver disease is warranted.