Publications by authors named "Lam Van Nguyen"

36 Publications

Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study.

Lancet Glob Health 2022 07;10(7):e989-e1002

National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.

Background: Encephalitis is a worldwide public health issue, with a substantially high burden among children in southeast Asia. We aimed to determine the causes of encephalitis in children admitted to hospitals across the Greater Mekong region by implementing a comprehensive state-of-the-art diagnostic procedure harmonised across all centres, and identifying clinical characteristics related to patients' conditions.

Methods: In this multicentre, observational, prospective study of childhood encephalitis, four referral hospitals in Cambodia, Vietnam, Laos, and Myanmar recruited children (aged 28 days to 16 years) who presented with altered mental status lasting more than 24 h and two of the following minor criteria: fever (within the 72 h before or after presentation), one or more generalised or partial seizures (excluding febrile seizures), a new-onset focal neurological deficit, cerebrospinal fluid (CSF) white blood cell count of 5 per mL or higher, or brain imaging (CT or MRI) suggestive of lesions of encephalitis. Comprehensive diagnostic procedures were harmonised across all centres, with first-line testing was done on samples taken at inclusion and results delivered within 24 h of inclusion for main treatable causes of disease and second-line testing was done thereafter for mostly non-treatable causes. An independent expert medical panel reviewed the charts and attribution of causes of all the included children. Using multivariate analyses, we assessed risk factors associated with unfavourable outcomes (ie, severe neurological sequelae and death) at discharge using data from baseline and day 2 after inclusion. This study is registered with ClinicalTrials.gov, NCT04089436, and is now complete.

Findings: Between July 28, 2014, and Dec 31, 2017, 664 children with encephalitis were enrolled. Median age was 4·3 years (1·8-8·8), 295 (44%) children were female, and 369 (56%) were male. A confirmed or probable cause of encephalitis was identified in 425 (64%) patients: 216 (33%) of 664 cases were due to Japanese encephalitis virus, 27 (4%) were due to dengue virus, 26 (4%) were due to influenza virus, 24 (4%) were due to herpes simplex virus 1, 18 (3%) were due to Mycobacterium tuberculosis, 17 (3%) were due to Streptococcus pneumoniae, 17 (3%) were due to enterovirus A71, 74 (9%) were due to other pathogens, and six (1%) were due to autoimmune encephalitis. Diagnosis was made within 24 h of admission to hospital for 83 (13%) of 664 children. 119 (18%) children had treatable conditions and 276 (42%) had conditions that could have been preventable by vaccination. At time of discharge, 153 (23%) of 664 children had severe neurological sequelae and 83 (13%) had died. In multivariate analyses, risk factors for unfavourable outcome were diagnosis of M tuberculosis infection upon admission (odds ratio 3·23 [95% CI 1·04-10·03]), coma on day 2 (2·90 [1·78-4·72]), supplementary oxygen requirement (1·89 [1·25-2·86]), and more than 1 week duration between symptom onset and admission to hospital (3·03 [1·68-5·48]). At 1 year after inclusion, of 432 children who were discharged alive from hospital with follow-up data, 24 (5%) had died, 129 (30%) had neurological sequelae, and 279 (65%) had completely recovered.

Interpretation: In southeast Asia, most causes of childhood encephalitis are either preventable or treatable, with Japanese encephalitis virus being the most common cause. We provide crucial information that could guide public health policy to improve diagnostic, vaccination, and early therapeutic guidelines on childhood encephalitis in the Greater Mekong region.

Funding: Institut Pasteur, Institut Pasteur International Network, Fondation Merieux, Aviesan Sud, INSERM, Wellcome Trust, Institut de Recherche pour le Développement (IRD), and Fondation Total.
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http://dx.doi.org/10.1016/S2214-109X(22)00174-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210261PMC
July 2022

Severe Recurrent Bacterial Pneumonia Among Children Living With HIV.

Pediatr Infect Dis J 2022 05;41(5):e208-e215

From the The Kirby Institute, UNSW Sydney, Australia.

Background: Bacterial pneumonia imparts a major morbidity and mortality burden on children living with HIV, yet effective prevention and treatment options are underutilized. We explored clinical factors associated with severe recurrent bacterial pneumonia among children living with HIV.

Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database were included if they started antiretroviral therapy (ART) on or after January 1st, 2008. Factors associated with severe recurrent bacterial pneumonia were assessed using competing-risk regression.

Results: A total of 3,944 children were included in the analysis; 136 cases of severe recurrent bacterial pneumonia were reported at a rate of 6.5 [95% confidence interval (CI): 5.5-7.7] events per 1,000 patient-years. Clinical factors associated with severe recurrent bacterial pneumonia were younger age [adjusted subdistribution hazard ratio (aHR): 4.4 for <5 years versus ≥10 years, 95% CI: 2.2-8.4, P < 0.001], lower weight-for-age z-score (aHR: 1.5 for <-3.0 versus >-2.0, 95% CI: 1.1-2.3, P = 0.024), pre-ART diagnosis of severe recurrent bacterial pneumonia (aHR: 4.0 versus no pre-ART diagnosis, 95% CI: 2.7-5.8, P < 0.001), past diagnosis of symptomatic lymphoid interstitial pneumonitis or chronic HIV-associated lung disease, including bronchiectasis (aHR: 4.8 versus no past diagnosis, 95% CI: 2.8-8.4, P < 0.001), low CD4% (aHR: 3.5 for <10% versus ≥25%, 95% CI: 1.9-6.4, P < 0.001) and detectable HIV viral load (aHR: 2.6 versus undetectable, 95% CI: 1.2-5.9, P = 0.018).

Conclusions: Children <10-years-old and those with low weight-for-age, a history of respiratory illness, low CD4% or poorly controlled HIV are likely to gain the greatest benefit from targeted prevention and treatment programs to reduce the burden of bacterial pneumonia in children living with HIV.
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http://dx.doi.org/10.1097/INF.0000000000003494DOI Listing
May 2022

Successful treatment of two extremely premature infants with perinatal tuberculosis and severe sepsis.

Clin Case Rep 2022 Feb 10;10(2):e05399. Epub 2022 Feb 10.

Center for Tropical Diseases National Children's Hospital Ha Noi Viet Nam.

Perinatal tuberculosis (TB) is a rare disease with severe clinical conditions that may spread to several organs. Early diagnosis to initiate an anti-TB regimen is key to saving patients. We report the successful treatment of two preterm babies with perinatal TB and sepsis at the National Children's Hospital (NCH), Vietnam.
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http://dx.doi.org/10.1002/ccr3.5399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831978PMC
February 2022

Alterations in children's sub-dominant gut microbiota by HIV infection and anti-retroviral therapy.

PLoS One 2021 11;16(10):e0258226. Epub 2021 Oct 11.

Department of Viral infection and International Health, Graduate school of Medical Science, Kanazawa University, Kanazawa, Japan.

Objective: We investigated the impact of human immunodeficiency virus (HIV) infection and anti-retroviral therapy (ART) on the gut microbiota of children.

Design: This cross-sectional study investigated the gut microbiota of children with and without HIV.

Methods: We collected fecal samples from 59 children with HIV (29 treated with ART [ART(+)] and 30 without ART [HIV(+)]) and 20 children without HIV [HIV(-)] in Vietnam. We performed quantitative RT-PCR to detect 14 representative intestinal bacteria targeting 16S/23S rRNA molecules. We also collected the blood samples for immunological analyses.

Results: In spearman's correlation analyses, no significant correlation between the number of dominant bacteria and age was found among children in the HIV(-) group. However, the number of sub-dominant bacteria, including Streptococcus, Enterococcus, and Enterobacteriaceae, positively correlated with age in the HIV(-) group, but not in the HIV(+) group. In the HIV(+) group, Clostridium coccoides group positively associated with the CD4+ cell count and its subsets. In the ART(+) group, Staphylococcus and C. perfringens positively correlated with CD4+ cells and their subsets and negatively with activated CD8+ cells. C. coccoides group and Bacteroides fragilis group were associated with regulatory T-cell counts. In multiple linear regression analyses, ART duration was independently associated with the number of C. perfringens, and Th17 cell count with the number of Staphylococcus in the ART(+) group.

Conclusions: HIV infection and ART may influence sub-dominant gut bacteria, directly or indirectly, in association with immune status in children with HIV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258226PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504761PMC
November 2021

Knowledge of Antiretroviral Treatment and Associated Factors in HIV-Infected Patients.

Healthcare (Basel) 2021 Apr 20;9(4). Epub 2021 Apr 20.

Department of Pharmacology and Clinical Pharmacy, Can Tho University of Medicine and Pharmacy, Can Tho City 900000, Vietnam.

This study aimed to assess the knowledge of antiretroviral (ARV) treatment and the associated factors in HIV-infected patients in Vietnam. We conducted a cross-sectional descriptive study of 350 human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients being treated with ARV at outpatient clinics at Soc Trang, Vietnam, from June 2019 to December 2019. Using an interview questionnaire, patients who answered at least eight out of nine questions correctly, including some required questions, were considered to have a general knowledge of ARV treatment. Using multivariate logistic regression to identify factors associated with knowledge of ARV treatment, we found that 62% of HIV-infected patients had a general knowledge of ARV treatment, with a mean score of 8.2 (SD 1.4) out of 9 correct. A higher education level ( < 0.001); working away from home ( = 0.013); getting HIV transmitted by injecting drugs or from mother-to-child contact ( = 0.023); the presence of tension, anxiety, or stress ( = 0.005); self-reminding to take medication ( = 0.024); and a high self-evaluated adherence ( < 0.001) were found to be significantly associated with an adequate knowledge of ARV treatment. In conclusion, education programs for patients, as well as the quality of medical services and support, should be strengthened.
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http://dx.doi.org/10.3390/healthcare9040483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073643PMC
April 2021

Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam.

Ther Adv Infect Dis 2020 Jan-Dec;7:2049936120958536. Epub 2020 Sep 17.

Training and Research Academic Collaboration (TRAC), Sweden, Vietnam.

Background: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the gag gene, particularly the important functional binding domains in relation to treatment outcomes.

Methods: HIV-infected children enrolled and treated at Vietnam National Children's Hospital were recruited in the study. A total of 25 gag sequences were generated and used to construct phylogenetic trees and aligned with a reference sequence comparing 17 functional domains.

Results: We found that all patients in a treatment failure (TF) group belonged to one cluster of the phylogenetic tree. In addition, the rate of mutations was significantly higher in TF compared with a treatment success (TS) group, specifically the PIP2 recognition motif, and the nucleocapsid basic and zinc motif 2 domains [median and (interquartile range (IQR): 12.5 (6.25-12.5) versus 50 (25-50), p < 0.01; 0 (0-0) versus 0 (0-21.43), p = 0.03 and 0 (0-7.14) versus 7.14 (7.14-7.14), p = 0.04, respectively]. When analyzing gag sequences at different time points in seven patients, we did not observe a consistent mutation pattern related to treatment response.

Conclusion: Gag mutations in certain domains might be associated with increased viral load; therefore, studying the molecular genotype of the gene might be beneficial in monitoring treatment response in HIV-infected children.
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http://dx.doi.org/10.1177/2049936120958536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502858PMC
September 2020

Characterization of envelope sequence of HIV virus in children infected with HIV in Vietnam.

SAGE Open Med 2020 25;8:2050312120937198. Epub 2020 Jun 25.

Training and Research Academic Collaboration (TRAC) - Sweden - Vietnam.

Background: HIV is characterized by high levels of genetic variability, including increased numbers of heterogeneous sequences of the envelope region. Therefore, studying genetic variability of HIV in relation to viral replication might facilitate prognosis of disease progression.

Methods: The study was designed as cross-sectional; data and samples of participants collected and analyzed genes were obtained from 23 children enrolled by Vietnam National Children's Hospital.

Results: Substantial mutations in the C2 region were found in patients with high levels of viral replication while changes in the C3 region were mostly found in patients with low viral load. In the V1 region, we found profound amino acid modifications in patients with low HIV viral loads in contrast to the V2 sequence, where we identified single point mutations in patients with increased HIV viral load. The V3 region was relatively homogeneous, while profound deletions in the V4 region were detected in patients with increased viral replication.

Conclusion: Our results suggest that genetic variations in different regions of the HIV envelope sequence, including both conserved C2 and C3 and variable V1/V2 and V4 regions, might be involved in increased viral infectivity and replication capacity. Such knowledge might help improve prediction of HIV progress and treatment in patients.
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http://dx.doi.org/10.1177/2050312120937198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323269PMC
June 2020

Identification, Management, and Outcomes of Combination Antiretroviral Treatment Failure in Adolescents With Perinatal Human Immunodeficiency Virus Infection in Asia.

Clin Infect Dis 2021 10;73(7):e1919-e1926

Kirby Institute, University of New South Wales, Sydney, Australia.

Background: Combination antiretroviral therapy (cART) failure is a major threat to human immunodeficiency virus (HIV) programs, with implications for individual- and population-level outcomes. Adolescents with perinatally acquired HIV infection (PHIVA) should be a focus for treatment failure given their poorer outcomes compared to children and adults.

Methods: Data (2014-2018) from a regional cohort of Asian PHIVA who received at least 6 months of continuous cART were analyzed. Treatment failure was defined according to World Health Organization criteria. Descriptive analyses were used to report treatment failure and subsequent management and evaluate postfailure CD4 count and viral load trends. Kaplan-Meier survival analyses were used to compare the cumulative incidence of death and loss to follow-up (LTFU) by treatment failure status.

Results: A total 3196 PHIVA were included in the analysis with a median follow-up period of 3.0 years, of whom 230 (7.2%) had experienced 292 treatment failure events (161 virologic, 128 immunologic, 11 clinical) at a rate of 3.78 per 100 person-years. Of the 292 treatment failure events, 31 (10.6%) had a subsequent cART switch within 6 months, which resulted in better immunologic and virologic outcomes compared to those who did not switch cART. The 5-year cumulative incidence of death and LTFU following treatment failure was 18.5% compared to 10.1% without treatment failure.

Conclusions: Improved implementation of virologic monitoring is required to realize the benefits of virologic determination of cART failure. There is a need to address issues related to accessibility to subsequent cART regimens, poor adherence limiting scope to switch regimens, and the role of antiretroviral resistance testing.
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http://dx.doi.org/10.1093/cid/ciaa872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492217PMC
October 2021

Determining standardized causes of death of infants, children, and adolescents living with HIV in Asia.

AIDS 2020 08;34(10):1527-1537

The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.

Objective: To implement a standardized cause of death reporting and review process to systematically disaggregate causes of HIV-related deaths in a cohort of Asian children and adolescents.

Design: Death-related data were retrospectively and prospectively assessed in a longitudinal regional cohort study.

Methods: Children under routine HIV care at sites in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam between 2008 and 2017 were followed. Causes of death were reported and then independently and centrally reviewed. Predictors were compared using competing risks survival regression analyses.

Results: Among 5918 children, 5523 (93%; 52% male) had ever been on combination antiretroviral therapy. Of 371 (6.3%) deaths, 312 (84%) occurred in those with a history of combination antiretroviral therapy (crude all-cause mortality 9.6 per 1000 person-years; total follow-up time 32 361 person-years). In this group, median age at death was 7.0 (2.9-13) years; median CD4 cell count was 73 (16-325) cells/μl. The most common underlying causes of death were pneumonia due to unspecified pathogens (17%), tuberculosis (16%), sepsis (8.0%), and AIDS (6.7%); 12% of causes were unknown. These clinical diagnoses were further grouped into AIDS-related infections (22%) and noninfections (5.8%), and non-AIDS-related infections (47%) and noninfections (11%); with 12% unknown, 2.2% not reviewed. Higher CD4 cell count and better weight-for-age z-score were protective against death.

Conclusion: Our standardized cause of death assessment provides robust data to inform regional resource allocation for pediatric diagnostic evaluations and prioritization of clinical interventions, and highlight the continued importance of opportunistic and nonopportunistic infections as causes of death in our cohort.
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http://dx.doi.org/10.1097/QAD.0000000000002583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487212PMC
August 2020

Dual Analysis of Loss to Follow-up for Perinatally HIV-Infected Adolescents Receiving Combination Antiretroviral Therapy in Asia.

J Acquir Immune Defic Syndr 2019 12;82(5):431-438

The Kirby Institute, UNSW Australia, Sydney, Australia.

Background: Perinatally HIV-infected adolescents (PHIVA) are an expanding population vulnerable to loss to follow-up (LTFU). Understanding the epidemiology and factors for LTFU is complicated by varying LTFU definitions.

Setting: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.

Methods: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.

Results: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation <5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.

Conclusions: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.
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http://dx.doi.org/10.1097/QAI.0000000000002184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857712PMC
December 2019

Peritransition Outcomes of Southeast Asian Adolescents and Young Adults With HIV Transferring From Pediatric to Adult Care.

J Adolesc Health 2020 01 15;66(1):92-99. Epub 2019 Oct 15.

HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Purpose: The aim of this article was to study the clinical and social outcomes of health care transition among Asian adolescents and young adults with HIV (AYHIV).

Methods: AYHIV who transferred from a pediatric to an adult clinic within the past year across five sites in Malaysia, Thailand, and Vietnam had clinical and laboratory evaluations and completed questionnaires about their health, socioeconomic factors, and transition experiences. Multiple logistic regression was used to assess associations with HIV viremia.

Results: Of 93 AYHIV enrolled between June 2016 and April 2017, 56% were female, 87% acquired HIV through perinatal exposure, median age was 20 years (interquartile range [IQR] 18.5-21). Two-thirds were in a formal education program, 43% were employed, 43% of females and 35% of males were sexually active. Median lifetime antiretroviral therapy duration was 6.2 years (IQR 3.3-10.7); 45% had received second-line therapy. Median CD4 was 601 cells/mm (IQR 477-800); 82% had HIV-RNA <40 copies/mL. Being in a relationship, a shorter posttransition duration, self-reported adherence of ≥95%, and higher CD4 were inversely associated with HIV viremia. Half felt very prepared for the transfer to adult care, and 20% frequently and 43% sometimes still met with pediatric providers. Two-thirds reported needing to keep their HIV a secret, and 23%-38% reported never or rarely having someone to discuss problems with.

Conclusions: Asian AYHIV in our cohort were concerned about the negative social impact of having and disclosing HIV, and one-third lacked people they could trust with their personal problems, which could have negative implications for their ability to navigate adult life.
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http://dx.doi.org/10.1016/j.jadohealth.2019.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928413PMC
January 2020

Mycobacterial Blood Culture for Diagnosis of Tuberculosis in Vietnamese Children.

Pediatr Infect Dis J 2019 11;38(11):e309-e312

Oxford University Clinical Research Unit, Hanoi, Vietnam.

Diagnosis of pediatric tuberculosis is notoriously difficult. We investigated the additional yield of blood culture in hospitalized children in Vietnam. Among 554 enrolled clinically suspected patients, an additional 6 cases were diagnosed, while the incremental cost per case was USD500. Addition of blood culture is therefore not recommended for our total patient population, but may be considered in specific groups.
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http://dx.doi.org/10.1097/INF.0000000000002457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198059PMC
November 2019

Impact of the frequency of plasma viral load monitoring on treatment outcomes among children with perinatally acquired HIV.

J Int AIDS Soc 2019 06;22(6):e25312

Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.

Introduction: Recommendations on the optimal frequency of plasma viral load (pVL) monitoring in children living with HIV (CLWH) who are stable on combination antiretroviral therapy (cART) are inconsistent. This study aimed to determine the impact of annual versus semi-annual pVL monitoring on treatment outcomes in Asian CLWH.

Methods: Data on children with perinatally acquired HIV aged <18 years on first-line, non-nucleoside reverse transcriptase inhibitor-based cART with viral suppression (two consecutive pVL <400 copies/mL over a six-month period) were included from a regional cohort study; those exposed to prior mono- or dual antiretroviral treatment were excluded. Frequency of pVL monitoring was determined at the site-level based on the median rate of pVL measurement: annual 0.75 to 1.5, and semi-annual >1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000 copies/mL), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL <400 copies/mL. Competing risk regression models were used to identify predictors of treatment failure.

Results: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi-annual pVL monitoring (n = 4) respectively. Pre-cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 log copies/mL. At baseline, the median age was 9.2 years, 64% were on nevirapine-based regimens, the median cART duration was 1.6 years, and the median CD4 percentage was 26%. Over the follow-up period, 258 (25%) CLWH with annual and 40 (23%) with semi-annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient-years of follow-up respectively (p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59).

Conclusions: Annual compared to semi-annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first-line NNRTI-based cART.
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http://dx.doi.org/10.1002/jia2.25312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556679PMC
June 2019

Determinants of Viral Resuppression or Persistent Virologic Failure After Initial Failure With Second-Line Antiretroviral Treatment Among Asian Children and Adolescents With HIV.

J Pediatric Infect Dis Soc 2020 Apr;9(2):253-256

TREAT Asia/amfAR-Foundation for AIDS Research, Bangkok, Thailand.

Of 56 children with perinatally acquired human immunodeficiency virus (HIV) who had been prescribed second-line protease inhibitor-based antiretroviral therapy and had ≥1 previous episode of viral failure (HIV RNA, ≥1000 copies/mL), 46% had ≥1, 34% had ≥2, and 23% had ≥3 consecutive episodes of viral failure during the 2 years of follow-up. Two of these children experienced a major protease inhibitor mutation.
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http://dx.doi.org/10.1093/jpids/piz034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368343PMC
April 2020

A Longitudinal Study of Behavioral Risk, Adherence, and Virologic Control in Adolescents Living With HIV in Asia.

J Acquir Immune Defic Syndr 2019 06;81(2):e28-e38

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

Background: Adolescents living with HIV (ALHIV) have poorer adherence and clinical outcomes than adults. We conducted a study to assess behavioral risks and antiretroviral therapy outcomes among ALHIV in Asia.

Methods: A prospective cohort study among ALHIV and matched HIV-uninfected controls aged 12-18 years was conducted at 9 sites in Malaysia, Thailand, and Vietnam from July 2013 to March 2017. Participants completed an audio computer-assisted self-interview at weeks 0, 48, 96, and 144. Virologic failure (VF) was defined as ≥1 viral load (VL) measurement >1000 copies/mL. Generalized estimating equations were used to identify predictors for VF.

Results: Of 250 ALHIV and 59 HIV-uninfected controls, 58% were Thai and 51% females. The median age was 14 years at enrollment; 93% of ALHIV were perinatally infected. At week 144, 66% of ALHIV were orphans vs. 28% of controls (P < 0.01); similar proportions of ALHIV and controls drank alcohol (58% vs. 65%), used inhalants (1% vs. 2%), had been sexually active (31% vs. 21%), and consistently used condoms (42% vs. 44%). Of the 73% of ALHIV with week 144 VL testing, median log VL was 1.60 (interquartile range 1.30-1.70) and 19% had VF. Over 70% of ALHIV had not disclosed their HIV status. Self-reported adherence ≥95% was 60% at week 144. Smoking cigarettes, >1 sexual partner, and living with nonparent relatives, a partner or alone, were associated with VF at any time.

Conclusions: The subset of ALHIV with poorer adherence and VF require comprehensive interventions that address sexual risk, substance use, and HIV-status disclosure.
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http://dx.doi.org/10.1097/QAI.0000000000002008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522277PMC
June 2019

Early and Late Virologic Failure After Virologic Suppression in HIV-Infected Asian Children and Adolescents.

J Acquir Immune Defic Syndr 2019 03;80(3):308-315

Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Background: Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving.

Setting: An Asian cohort in 16 pediatric HIV services across 6 countries.

Methods: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA ≥1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA ≥1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure.

Results: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure.

Conclusions: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required.
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http://dx.doi.org/10.1097/QAI.0000000000001921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952284PMC
March 2019

Disease- and Treatment-related Morbidity in Adolescents With Perinatal HIV Infection in Asia.

Pediatr Infect Dis J 2019 03;38(3):287-292

From the The Kirby Institute, UNSW, Sydney, Australia.

Background: Perinatally HIV-infected adolescents (PHIVA) are exposed to a chronic systemic infection and long-term antiretroviral therapy (ART), leaving them susceptible to morbidities associated with inflammation, immunodeficiency and drug toxicity.

Methods: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria.

Results: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years.

Conclusions: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.
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http://dx.doi.org/10.1097/INF.0000000000002208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375771PMC
March 2019

Characteristics, mortality and outcomes at transition for adolescents with perinatal HIV infection in Asia.

AIDS 2018 07;32(12):1689-1697

Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.

Objectives: The aim of this study was to describe characteristics of perinatally HIV-infected adolescents (PHIVAs), factors associated with mortality, and outcomes at transition.

Design: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia.

Methods: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation.

Results: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% had CD4+ cell count less than 500 cells/μl and 51.1% had experienced a WHO stage III/IV clinical event. At transition, 38.9% had CD4+ cell count less than 500 copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality rate was 0.71 per 100 person-years, with HIV RNA ≥1000 copies/ml, CD4+ cell count less than 500 cells/μl, height-for-age or weight-for-age z-score less than -2, history of a WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART.

Conclusion: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition.
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http://dx.doi.org/10.1097/QAD.0000000000001883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084456PMC
July 2018

Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort.

J Acquir Immune Defic Syndr 2018 06;78(2):221-230

Department of Epidemiology, Fairbanks School of Public Health, Indianapolis, IN.

Background: Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line.

Methods: Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event.

Results: In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor-based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively.

Conclusions: High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years.
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http://dx.doi.org/10.1097/QAI.0000000000001667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953797PMC
June 2018

Adherence to antiretroviral therapy, stigma and behavioral risk factors in HIV-infected adolescents in Asia.

AIDS Care 2018 06 16;30(6):727-733. Epub 2018 Jan 16.

b TREAT Asia/amfAR-The Foundation for AIDS Research , Bangkok , Thailand.

We studied behavioral risks among HIV-infected and uninfected adolescents using an audio computer-assisted self-interview. A prospective cohort study was initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected adolescents were matched to uninfected adolescents (4:1) by sex and age group (12-14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5 years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1 years) adolescents. At enrollment, HIV-infected adolescents were on antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14% had HIV-RNA >1000 copies/mL; 19% reported adherence <80%. Eighty-four (34%) HIV-infected and 26 (44%) uninfected adolescents reported having ever smoked cigarettes or drunk alcohol (p = 0.13); 10% of HIV-infected and 17% of uninfected adolescents reported having initiated sexual activity; 6 of the HIV-infected adolescents had HIV-RNA >1000 copies/mL. Risk behaviors were common among adolescents, with few differences between those with and without HIV.
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http://dx.doi.org/10.1080/09540121.2018.1425363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912939PMC
June 2018

Effects of Short-Term Probiotic Ingestion on Immune Profiles and Microbial Translocation among HIV-1-Infected Vietnamese Children.

Int J Mol Sci 2017 Oct 19;18(10). Epub 2017 Oct 19.

Department of Viral infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan.

Here, we investigated the effects of the probiotic strain Shirota (LcS) on immune profiles and intestinal microbial translocation among children infected with human immunodeficiency virus (HIV). This prospective study included 60 HIV-infected children-including 31 without antiretroviral therapy (ART) (HIV(+)) and 29 who received ART for a median of 3.5 years (ART(+)) and 20 children without HIV infection (HIV(-)). Participants were recruited in Vietnam. All children were given fermented milk containing LcS (6.5 × 10⁸ cfu) daily for 8 weeks. Before and after LcS ingestion, blood samples were collected for virological, immunological, and bacteriological analyses. After LcS ingestion, peripheral CD4⁺ T-cell and Th2 (CXCR3CCR6CD4⁺) counts significantly increased in both HIV-infected groups; Th17 (CXCR3CCR6⁺CD4⁺) counts increased in all three groups; regulatory T-cell (CD25CD4⁺) counts decreased in the ART(+) and HIV(-) groups; activated CD8⁺ cells (CD38⁺HLA-DR⁺CD8⁺) decreased from 27.5% to 13.2% ( < 0.001) in HIV(+) children; and plasma HIV load decreased slightly but significantly among HIV(+) children. No group showed a significantly altered frequency of bacterial 16S/23S rRNA gene detection in the plasma. No serious adverse events occurred. These findings suggest that short-term LcS ingestion is a safe supportive approach with immunological and virological benefits in HIV-infected children.
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http://dx.doi.org/10.3390/ijms18102185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666866PMC
October 2017

Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy.

J Adolesc Health 2017 Jul 24;61(1):91-98. Epub 2017 Mar 24.

Faculty of Medicine, The Kirby Institute, UNSW Australia, Sydney, Australia.

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] <400 copies/mL ≥6 months apart) were included. Baseline was the date of the first VL <400 copies/mL at age ≥10 years or the 10th birthday for those with prior suppression. Cox proportional hazards models were used to identify predictors of postsuppression VR (VL >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; 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 <-2.5), being raised by grandparents, receiving second-line protease inhibitor-based regimens, starting combination antiretroviral therapy after 2005, and having preadolescent VF were independent predictors of adolescent VR. At VR, median age, CD4 cell count, and VL (IQR) were 14.8 (13.2-16.4) years, 507 (325-723) cells/mm, and 4.1 (3.5-4.7) log 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.
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http://dx.doi.org/10.1016/j.jadohealth.2017.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483211PMC
July 2017

Whole-Genome Characteristics and Polymorphic Analysis of Vietnamese Rice Landraces as a Comprehensive Information Resource for Marker-Assisted Selection.

Int J Genomics 2017 7;2017:9272363. Epub 2017 Feb 7.

Department of Genetic Engineering, Agricultural Genetics Institute, Vietnam Academy of Agricultural Sciences, Km2 Pham Van Dong, Tuliem, Hanoi, Vietnam.

Next generation sequencing technologies have provided numerous opportunities for application in the study of whole plant genomes. In this study, we present the sequencing and bioinformatic analyses of five typical rice landraces including three and two with potential blast resistance. A total of 688.4 million 100 bp paired-end reads have yielded approximately 30-fold coverage to compare with the Nipponbare reference genome. Among them, a small number of reads were mapped to both chromosomes and organellar genomes. Over two million and eight hundred thousand single nucleotide polymorphisms (SNPs) and insertions and deletions (InDels) in and lines have been determined, which potentially have significant impacts on multiple transcripts of genes. SNP deserts, contiguous SNP-low regions, were found on chromosomes 1, 4, and 5 of all genomes of rice examined. Based on the distribution of SNPs per 100 kilobase pairs, the phylogenetic relationships among the landraces have been constructed. This is the first step towards revealing several salient features of rice genomes in Vietnam and providing significant information resources to further marker-assisted selection (MAS) in rice breeding programs.
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http://dx.doi.org/10.1155/2017/9272363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318636PMC
February 2017

Short Communication: Impact of Viral Load Use on Treatment Switch in Perinatally HIV-Infected Children in Asia.

AIDS Res Hum Retroviruses 2017 03 31;33(3):230-233. Epub 2016 Oct 31.

17 TREAT Asia/amfAR-The Foundation for AIDS Research , Bangkok, Thailand .

We sought to assess the impact of routine HIV viral load (VL) monitoring on the incidence of switching from a first- to a second-line antiretroviral therapy (ART) regimen, and to describe factors associated with switch. Data from a regional cohort of 16 clinical programs in six Asian countries were analyzed. Second-line switch was defined as a change from a non-nucleoside reverse transcriptase inhibitor (NNRTI) to a protease inhibitor (PI) or vice versa, and ≥1 of the following: (1) reported treatment failure by local criteria, (2) switch of ≥1 additional drug, or (3) a preceding HIV VL ≥1,000 copies/ml. Routine VL was having ≥1 test after ≥24 weeks of ART and ≥1 time/year thereafter. Factors associated with time to switch were evaluated with death and loss to follow-up as competing risks. A total of 2,398 children were included in this analysis. At ART initiation, the median (interquartile range) age was 6.0 (3.3-8.9) years, more than half had WHO stage 3 or 4, the median CD4 was 189 (47-456) cells/mm, 93% were on NNRTI-based first-line ART, and 34% had routine VL monitoring. Treatment switch occurred in 17.6% of patients, at a median of 35 (22-49) months. After adjusting for country, sex, first ART regimen, and CD4% at ART initiation, children with routine VL monitoring were 1.46 (95% confidence interval 1.11-1.93) times more likely to be switched (p = .007). Scale-up of VL testing will lead to earlier identification of treatment failure, and it can help guide earlier switches to prevent resistance.
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http://dx.doi.org/10.1089/AID.2016.0039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333561PMC
March 2017

Impact of orphan status on HIV treatment outcomes and retention in care of children and adolescents in Asia.

J Virus Erad 2016 Oct 5;2(4):227-231. Epub 2016 Oct 5.

TREAT Asia/amfAR - The Foundation for AIDS Research , Bangkok , Thailand .

An analysis of the impact of orphanhood at antiretroviral therapy (ART) initiation on HIV outcomes in Asia included 4300 children; 51% were male. At ART initiation, 1805 (42%) were non-orphans (median age: 3 years), 1437 (33%) were single orphans (6 years) and 1058 (25%) were double orphans (7 years). Ten-year post-ART survival was 93.4-95.2% across orphan categories. Clinic transfers were higher among single and double orphans than non-orphans (41% 11%, <0.001). On multivariate analysis, children ≥3 years at ART initiation (hazard ratio 1.58 <3 years, 95% confidence interval: 1.11-2.24) were more likely to be lost to follow-up. Although post-ART mortality and retention did not differ by orphan status, orphans were at greater risk of starting ART at older ages, and with more severe immunosuppression and poorer growth.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075350PMC
October 2016

Therapeutic Drug Monitoring of Lopinavir in HIV-Infected Children on Second-Line Antiretroviral Therapy in Asia.

Ther Drug Monit 2016 12;38(6):791-795

*Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; †The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‡Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; §Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand; ¶Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; ‖Children's Hospital 1, Ho Chi Minh City, Vietnam; **Children's Hospital 2, Ho Chi Minh City, Vietnam; ††National Hospital of Pediatrics, Hanoi, Vietnam; ‡‡Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; §§TREAT Asia/amfAR-The Foundation for AIDS Research, Bangkok, Thailand; ¶¶The Kirby Institute, UNSW Australia, Sydney, Australia; and ‖‖Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.

Background: 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.

Methods: 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.

Results: 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 concentrations <1.0 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 concentrations <1.0 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 RNA >1000 copies per milliliter. No factors predicted major LPV resistance mutations.

Conclusions: The authors support that the DHHS target LPV concentration of <1.0 mg/L is predictive of VF, but not of the presence of major LPV mutations.
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http://dx.doi.org/10.1097/FTD.0000000000000329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112108PMC
December 2016

Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam.

Int J Mol Sci 2016 Aug 2;17(8). Epub 2016 Aug 2.

Department of Viral Infection and International Health, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan.

CD4⁺ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(-)) aged 2-12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4⁺-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38⁺HLA (human leukocyte antigen)-DR⁺CD8⁺- (activated CD8⁺) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(-) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8⁺-cell activation status. Among the ART(+) children, the total CD4⁺-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8-8.3 years, whereas Th1 counts and the CD8⁺-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8⁺ cells and monocytes, and ART induced rapid Th1 recovery and early CD8⁺-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring.
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http://dx.doi.org/10.3390/ijms17081245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000643PMC
August 2016

Early Height and Weight Changes in Children Using Cotrimoxazole Prophylaxis With Antiretroviral Therapy.

Clin Infect Dis 2016 11 28;63(9):1236-1244. Epub 2016 Jul 28.

The Kirby Institute, University of New South Wales, Sydney, Australia.

Background: The growth benefits of cotrimoxazole during early antiretroviral therapy (ART) are not well characterized.

Methods: Individuals enrolled in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database were included if they started ART at ages 1 month-14 years and had both height and weight measurements available at ART initiation (baseline). Generalized estimating equations were used to identify factors associated with change in height-for-age z-score (HAZ), follow-up HAZ ≥ -2, change in weight-for-age z-score (WAZ), and follow-up WAZ ≥ -2.

Results: A total of 3217 children were eligible for analysis. The adjusted mean change in HAZ among cotrimoxazole and non-cotrimoxazole users did not differ significantly over the first 24 months of ART. In children who were stunted (HAZ < -2) at baseline, cotrimoxazole use was not associated with a follow-up HAZ ≥ -2. The adjusted mean change in WAZ among children with a baseline CD4 percentage (CD4%) >25% became significantly different between cotrimoxazole and non-cotrimoxazole users after 6 months of ART and remained significant after 24 months (overall P < .01). Similar changes in WAZ were observed in those with a baseline CD4% between 10% and 24% (overall P < .01). Cotrimoxazole use was not associated with a significant difference in follow-up WAZ in children with a baseline CD4% <10%. In those underweight (WAZ < -2) at baseline, cotrimoxazole use was associated with a follow-up WAZ ≥ -2 (adjusted odds ratio, 1.70 vs not using cotrimoxazole [95% confidence interval, 1.28-2.25], P < .01). This association was driven by children with a baseline CD4% ≥10%.

Conclusions: Cotrimoxazole use is associated with benefits to WAZ but not HAZ during early ART in Asian children.
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http://dx.doi.org/10.1093/cid/ciw514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064162PMC
November 2016

Transcriptome sequencing and comparative analysis of Schizochytrium mangrovei PQ6 at different cultivation times.

Biotechnol Lett 2016 Oct 9;38(10):1781-9. Epub 2016 Jul 9.

Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.

Objective: The heterotrophic marine microalga, Schizochytrium mangrovei PQ6, synthesizes large amounts of polyunsaturated fatty acids (PUFAs) with possible nutritional applications. We characterized the transcriptome of S. mangrovei PQ6, focusing on lipid metabolism pathways throughout growth.

Result: Cell growth, total lipid, and docosahexaenoic acid (DHA, 22:6n-3) contents of S. mangrovei PQ6 in 500 ml batch cultures rapidly increased on day 1 in cultivation and reached their maximum levels on day 5. Maximum lipid accumulation in 500 ml batch cultures occurred on day 5, with total lipid and DHA contents reaching 33.2 ± 1.25% of dry cell weight (DCW) and 136 mg/g DCW, respectively. 11,025 unigenes, 28,617 unigenes and 18,480 unigenes from the transcriptomes of samples collected on day 1, 3, and 5 in cultivation were identified, respectively. These unigenes of the three samples were further assembled into 30,782 unigenes with an average size of 673 bp and N50 of 950 bp, and a total of 9,980 unigenes were annotated in public protein databases. 93 unigenes involved in lipid metabolism in which expression patterns corresponded with total lipid and DHA accumulation patterns were identified.

Conclusion: The possible roles of PUFAs pathways, such as those mediated by fatty acid synthase, polyketide synthase, and desaturase/elongase, co-exist in S. mangrovei PQ6.
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http://dx.doi.org/10.1007/s10529-016-2165-5DOI Listing
October 2016
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