Publications by authors named "Thanyawee Puthanakit"

167 Publications

Acceptability of blood-based HIV self-testing among adolescents aged 15-19 years at risk of HIV acquisition in Bangkok.

Int J STD AIDS 2021 Apr 23:9564624211003742. Epub 2021 Apr 23.

Faculty of Medicine, Department of Pediatrics, 26683Chulalongkorn University, Bangkok, Thailand.

Introduction: Young men who have sex with men (YMSM) and young transgender women (YTGW) in Thailand are at high HIV risk. HIV self-tests (HIVSTs) are rapidly administrable and prompt linkage to HIV treatment or prevention services. This study assesses the acceptability and feasibility of blood-based HIVST use in adolescents.

Methods: A cross-sectional study was conducted among YMSM and YTGW aged 15-19 years with HIV acquisition risk. Participants completed questionnaires on the HIVST and then administered INSTI® independently, an HIVST immunoassay detecting gp41 and gp36 antibodies from finger-stick blood. Confirmatory HIV antibody tests were performed.

Results: Between July and September 2020, 90 adolescents were enrolled. Mean (SD) age was 17.6 (1.1) years. Half ( = 45) were YMSM. Forty-six (51%) were first-time HIV testers, and 32 (36%) had "ever used" HIV pre-exposure prophylaxis (PrEP). Two (2.2%, 95% CI: 0.0-5.3) tested positive, 21 (23.4%) invalid, and 67 (74.4%) negative. Invalidity causes included 17 (81%) insufficient blood, 3 (14%) buffer spillage, and 1 (5%) procedural missteps; all had negative HIV antibody tests. HIV self-test acceptability was 87.8% (95% CI: 81.0-94.5). Most (79%) preferred HIVST performance in hospital rather than at home.

Conclusions: HIVSTs are acceptable in HIV at-risk adolescents. Blood-based HIVSTs should be positioned as rapid point-of-care tests with real-time linkage to HIV services.
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http://dx.doi.org/10.1177/09564624211003742DOI Listing
April 2021

No increased acute kidney injury rate through giving an intravenous colistin loading dose in pediatric patients.

Int J Infect Dis 2021 Mar 23;106:91-97. Epub 2021 Mar 23.

Center of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address:

Objectives: A colistin loading dose is required to achieve adequate drug exposure for the treatment of multidrug-resistant Gram-negative bacteria. However, data on acute kidney injury (AKI) rates associated with this approach in children have been unavailable. The aim of this study was to examine AKI rates in children who were prescribed a colistin loading dose.

Methods: A retrospective study was conducted in patients aged 1 month to 18 years who had received intravenous colistin for ≥48 h. Loading dose (LD) was defined as colistin methanesulfonate at 4-5 mg of colistin base activity/kg/dose. AKI was defined according to KDIGO serum creatinine (SCr) criteria - SCr ≥ 1.5 times the baseline, measured 3-7 days after colistin initiation. Augmented renal clearance (ARC) was defined as an estimated glomerular filtration rate (eGFR) >150 mL/min/1.73 m. The rates of AKI were compared between children receiving or not receiving an LD, and between different eGFR groups.

Results: In total, 181 children were enrolled. The mean age was 4.3 years (95% confidence interval [CI], 3.6-4.9 years). Ninety-five of the subjects (52.5%) were male. There were 157 children with a baseline eGFR of ≥ 80 mL/min/1.73 m. The overall AKI rate within the first week in this group was 20.4% (95% CI, 14.4-27.6%): LD, 16.1% vs no LD, 23.2% (p = 0.29). Subgroup analysis, excluding patients with ARC, showed a lower AKI rate of 12.8% (95% CI, 6.8-21.3%): LD, 9.7% vs no LD, 14.3% (p = 0.53).

Conclusions: AKI rate was not different among children who received an intravenous colistin loading dose. This approach should be implemented to ensure the necessary drug exposure required for good treatment outcomes.
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http://dx.doi.org/10.1016/j.ijid.2021.03.059DOI Listing
March 2021

Acceptance and Outcome of Interventions in Meropenem De-escalation ASP in Pediatrics.

Pediatr Int 2021 Mar 19. Epub 2021 Mar 19.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: A prospective audit and feedback is a method that allows the antimicrobial stewardship program (ASP) team to interact with the attending physicians to tailor antibiotic therapy, including de-escalation, as appropriate. This study aimed to evaluate the acceptance and outcomes of an ASP de-escalation recommendation in children who received meropenem.

Methods: A prospective cohort study was conducted in children aged 1 month to 18 years who received meropenem in a tertiary care teaching hospital. The ASP team gave the recommendation between 72 and 120 hours after initiating meropenem therapy. Acceptance of de-escalation recommendation among primary physicians was evaluated within 24 hours of recommendation. Outcomes included clinical success rate at the 7 day and incidence rate of acquisition of carbapenem-resistant Gram-negative bacteria (CR-GNB) within 30 days.

Results: From March to December 2019, 217 children with the median (IQR) age of 2.1 (0.6,9.5) years received meropenem. The ASP team gave the recommendation as 127 (58.5%) cases of continuation and 90 (41.5%) cases of de-escalation. The overall acceptance of ASP de-escalation recommendation was 57.8% (95%CI 46.9-68.1%). The clinical success rates were 85.2% in the accepted group compared to 77.5% in the rejected group (p=0.06). The incidence rate of acquisition CR-GNB within 30 days after treatment was 5.8% in the accepted group and 15.8% in the rejected group (p=0.03).

Conclusions: About half of the recommendations to de-escalate meropenem prescriptions were accepted through ASP intervention. CR-GNB acquisitions were less likely in the de-escalation group. For carbapenem use to combat multidrug-resistant organisms, a proper de-escalation strategy after the initial 72-hours should be encouraged.
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http://dx.doi.org/10.1111/ped.14703DOI Listing
March 2021

Acceptance and Outcome of Interventions in Meropenem De-escalation ASP in Pediatrics.

Pediatr Int 2021 Mar 19. Epub 2021 Mar 19.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: A prospective audit and feedback is a method that allows the antimicrobial stewardship program (ASP) team to interact with the attending physicians to tailor antibiotic therapy, including de-escalation, as appropriate. This study aimed to evaluate the acceptance and outcomes of an ASP de-escalation recommendation in children who received meropenem.

Methods: A prospective cohort study was conducted in children aged 1 month to 18 years who received meropenem in a tertiary care teaching hospital. The ASP team gave the recommendation between 72 and 120 hours after initiating meropenem therapy. Acceptance of de-escalation recommendation among primary physicians was evaluated within 24 hours of recommendation. Outcomes included clinical success rate at the 7 day and incidence rate of acquisition of carbapenem-resistant Gram-negative bacteria (CR-GNB) within 30 days.

Results: From March to December 2019, 217 children with the median (IQR) age of 2.1 (0.6,9.5) years received meropenem. The ASP team gave the recommendation as 127 (58.5%) cases of continuation and 90 (41.5%) cases of de-escalation. The overall acceptance of ASP de-escalation recommendation was 57.8% (95%CI 46.9-68.1%). The clinical success rates were 85.2% in the accepted group compared to 77.5% in the rejected group (p=0.06). The incidence rate of acquisition CR-GNB within 30 days after treatment was 5.8% in the accepted group and 15.8% in the rejected group (p=0.03).

Conclusions: About half of the recommendations to de-escalate meropenem prescriptions were accepted through ASP intervention. CR-GNB acquisitions were less likely in the de-escalation group. For carbapenem use to combat multidrug-resistant organisms, a proper de-escalation strategy after the initial 72-hours should be encouraged.
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http://dx.doi.org/10.1111/ped.14703DOI Listing
March 2021

ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing.

BMC Infect Dis 2021 Jan 4;21(1). Epub 2021 Jan 4.

Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom.

Background: Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development.

Methods: ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks.

Results: Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9-18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls.

Conclusions: By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children.

Trial Registration: NCT, NCT02259127 , registered 7th October 2014; EUDRACT, 2014-002632-14, registered 18th June 2014 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES ); ISRCTN, ISRCTN91737921 , registered 4th October 2014.
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http://dx.doi.org/10.1186/s12879-020-05672-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809782PMC
January 2021

Federated Learning used for predicting outcomes in SARS-COV-2 patients.

Res Sq 2021 Jan 8. Epub 2021 Jan 8.

'Federated Learning' (FL) is a method to train Artificial Intelligence (AI) models with data from multiple sources while maintaining anonymity of the data thus removing many barriers to data sharing. During the SARS-COV-2 pandemic, 20 institutes collaborated on a healthcare FL study to predict future oxygen requirements of infected patients using inputs of vital signs, laboratory data, and chest x-rays, constituting the "EXAM" (EMR CXR AI Model) model. EXAM achieved an average Area Under the Curve (AUC) of over 0.92, an average improvement of 16%, and a 38% increase in generalisability over local models. The FL paradigm was successfully applied to facilitate a rapid data science collaboration without data exchange, resulting in a model that generalised across heterogeneous, unharmonized datasets. This provided the broader healthcare community with a validated model to respond to COVID-19 challenges, as well as set the stage for broader use of FL in healthcare.
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http://dx.doi.org/10.21203/rs.3.rs-126892/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805458PMC
January 2021

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

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

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

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

High prescribing rates of third-generation cephalosporins in children hospitalized with acute lower respiratory infections at a university hospital.

Int J Infect Dis 2021 Jan 10;102:369-374. Epub 2020 Nov 10.

Division of Paediatric Infectious Diseases, Department of Paediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Centre of Excellence for Paediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Objective: Antibiotics are frequently prescribed for the treatment of acute lower respiratory infections (ALRI) in children ≤5 years of age, even though viral aetiologies are the most common. The aim of this study was to describe antibiotic prescribing rates and patterns in children ≤5 years of age hospitalized with ALRI.

Methods: A retrospective study was conducted involving patients aged 1 month to 5 years hospitalized with ALRI at a university hospital. Patient demographics, ALRI diagnosis, microbiological data, antibiotics prescribed, and treatment outcomes were recorded and analysed.

Results: A total of 1283 patients were enrolled. Their median age was 1.6 years (interquartile range 0.8-2.8 years). Thirty-six percent had a co-morbidity. The diagnosis at discharge was viral ALRI in 81% and bacterial pneumonia in 19%. The mortality rate was 0.4%. The overall antibiotic prescribing rate was 46% (95% confidence interval 43-49%). Antibiotic prescribing rates were higher among children with co-morbidities (65% vs 35%, p < 0.001) and older children (57% for >2-5 years vs 39% for ≤2 years, p < 0.001). Parenteral third-generation cephalosporins were prescribed in up to 68% of all prescriptions.

Conclusions: Nearly-half of hospitalized children with ALRI were prescribed antibiotics. The majority of prescribed antibiotics were third-generation cephalosporins. An antimicrobial stewardship programme and antibiotic guidelines should be implemented to promote the judicious use of antibiotics.
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http://dx.doi.org/10.1016/j.ijid.2020.10.105DOI Listing
January 2021

Effects of vitamin D and calcium supplementation on bone mineral density among Thai youth using daily HIV pre-exposure prophylaxis.

J Int AIDS Soc 2020 10;23(10):e25624

Department of Paediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Introduction: Tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) is used for HIV pre-exposure prophylaxis (PrEP). TDF may affect bone mineral density (BMD), particularly in youth who are at a stage of peak bone mass accrual. The objective of this study was to evaluate the effect of vitamin D and calcium supplementation on BMD among Thai youth receiving daily oral PrEP.

Methods: This open-label randomized trial was conducted in male youth aged between 15 and 24 years. Participants were randomized to Arm A who received once-daily TDF/FTC plus vitamin D3 and calcium supplementation with meals twice daily (400 units of vitamin D3 and 1200 mg of elemental calcium/day) or Arm B who received once-daily TDF/FTC only. PrEP users were defined as taking at least two tablets/week (tenofovir-diphosphate level of >350 fmol/punch). Adherence to vitamin D/calcium supplementation was defined as self-reported adherence of >50%. Lumbar spine (L2-L4) BMD (LSBMD) was evaluated by dual-energy X-ray absorptiometry scan zero and six months after PrEP initiation.

Results: From March 2019 to March 2020, 100 youth were enrolled. Baseline characteristics between the two arms were similar. Median (IQR) age was 18 (17 to 20) years. At entry, median (IQR) LSBMD z-score was -0.8 (-1.5 to -0.3), 17% had low LSBMD (Z-score < -2). The median amount of calcium intake from nutritional three-day recall was 167 (IQR 94 to 272) mg/day, 39% of participants had vitamin D deficiency, defined as 25(OH)D levels <20 IU/mL. At six months, 79 participants were evaluated. Of these, 42 (52%) were PrEP takers and 25 of 38 (66%) of arm A participants had good adherence to vitamin D/calcium supplementation. Significantly higher proportions of youth in arm A compared to arm B had >3% increase in LSBMD at month 6 compared to baseline (67.6% vs. 42.9% respectively; p = 0.03). There were significantly higher increases in LSBMD among youth with vitamin D deficiency who were supplemented; arm A + 0.05 (0 to 0.05) compared to arm B + 0.03 (-0.1 to 0.03), p = 0.04.

Conclusions: Increases in LSBMD over six months among youth using PrEP who received vitamin D/calcium supplementation was greater than those not supplemented. Long-term follow-up should be considered to explore long-term outcomes.
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http://dx.doi.org/10.1002/jia2.25624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548100PMC
October 2020

Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019.

PLoS One 2020 9;15(10):e0240502. Epub 2020 Oct 9.

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: A greater understanding of the antibody response to SARS-CoV-2 in an infected population is important for the development of a vaccination.

Aim: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19.

Methods: Plasma from the following patient groups was examined: 118 adult patients with confirmed SARS-CoV-2 infections, 49 patients under investigation (without confirmed infections), 20 patients with other respiratory infections, and 102 healthy control patients. Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from EUROIMMUN was performed to assess for IgA and IgG antibodies. The optical density (OD) ratio cutoff for a positive result was 1.1 for IgA and 0.8 for IgG. Additionally, the association of the antibody response with both the severity of disease and the date after onset of symptoms was analyzed.

Results: A total of 289 participants were enrolled and 384 samples analyzed from March 10 to May 31, 2020. Patients were categorized, based on their clinical manifestations, as mild (n = 59), moderate (n = 27), or severe (n = 32). The overall sensitivity of IgA and IgG from the samples collected after day 7 of the symptoms was 87.9% (95% CI: 79.8-93.6) and 84.8% (95% CI: 76.2-91.3), respectively. Compared to the mild group, the severe group had significantly higher levels of spike 1 (S1) antigen-specific IgA and IgG. All patients in the moderate and severe groups had S1-specific IgG, while 20% of the patients in the mild group did not have any IgG detected after two weeks after the onset of symptoms. Interestingly, in the severe group, the SARS-CoV-2 IgG level was significantly higher in males than females (p = 0.003).

Conclusion: The serological test for SARS-CoV-2 has a high sensitivity more than two weeks after the onset of illness. Additionally, the serological response differs among patients based on sex as well as the severity of infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240502PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546485PMC
October 2020

Pediatric and Neonatal Invasive Candidiasis: Species Distribution and Mortality Rate in a Thai Tertiary Care Hospital.

Pediatr Infect Dis J 2021 Feb;40(2):96-102

From the Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Invasive candidiasis (IC) is a serious infection among children with underlying medical conditions. A shift from C. albicans to non-albicans Candida has been observed worldwide. This study aims to identify species of Candida and factors associated with the overall 30-day mortality rate.

Methods: A retrospective chart review was conducted among children with culture-confirmed IC from birth to 15 years of age at King Chulalongkorn Memorial Hospital, Thailand. Multivariate Cox regression analysis was performed to determine associated factors with 30-day mortality.

Results: From 2003 to 2019, 102 episodes of IC in pediatric group with a median age of 16 months (interquartile range 4-65) and 12 episodes of IC in neonatal group with a median age of 18 days (interquartile range 12-22). The species distribution were Candida albicans (35%), Candida parapsilosis (26%), Candida tropicalis (22%), Candida glabrata (6%) and other/unspecified species (11%). Antifungal treatment was given in 88% (67% Amphotericin B deoxycholate, 28% Fluconazole). Overall 30-day mortality rates were 28.5% [95% confidence interval (CI) 20.8%-38.4%] and 8.3% (95% CI 1.2%-46.1%) in pediatrics and neonates, respectively. Mortality rate among the neutropenic group was significantly higher than non-neutropenic group (46.4% vs. 20.6%, P = 0.005). Factors associated with 30-day mortality in pediatric IC were shock [adjusted hazard ratio (aHR) 4.2; 95% CI 1.8-9.4], thrombocytopenia (aHR 7.7; 95% CI 1.8-33.9) and no antifungal treatment (aHR 4.6; 95% CI 1.7-12.1).

Conclusions: Two-third of children with IC were diagnosed with non-albicans Candida. Children with high mortality rate included those with neutropenia, presented with shock or thrombocytopenia, such that the proper empiric antifungal treatment is recommended.
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http://dx.doi.org/10.1097/INF.0000000000002912DOI Listing
February 2021

Skin manifestations in COVID-19: The tropics experience.

J Dermatol 2020 Dec 2;47(12):e444-e446. Epub 2020 Sep 2.

Division of Dermatology, Department of Medicine, Faculty of Medicine, Skin and Allergy Research Unit, Chulalongkorn University, Bangkok, Thailand.

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http://dx.doi.org/10.1111/1346-8138.15567DOI Listing
December 2020

Rapid antiretroviral initiation among Thai youth living with HIV in the National AIDS programme in the era of treatment at any CD4 cell count: a national registry database study.

J Int AIDS Soc 2020 09;23 Suppl 5:e25574

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

Introduction: The process indicators of ending the HIV epidemic include 90% of people living with HIV receiving antiretroviral therapy (ART). The population of youth, however, has less access to healthcare. We assessed ART initiation and attrition outcomes of the HIV continuum from HIV diagnosis to ART initiation in youth living with HIV (YLHIV) and factors associated with ART initiation.

Methods: We studied YLHIV aged 15 to 24 years who were registered on the National AIDS Program (NAP) from January 2008 to May 2019. The study period was divided into 2008 to 2013 (initiated ART by CD4-guided criteria) and 2014 to 2018 (initiate ART at any CD4). Date of registration was used as a surrogate for the diagnosis date and defined as the baseline. The database included ART prescription and laboratory results, and the vital status was linked daily with the National Death Registry. Competing risk methods were used to assess factors associated with accessing ART, with loss to follow-up (LTFU) and death considered as competing events. Logistic regression was used to assess factors associated with rapid ART initiation, defined as initiation ≤1 month after registration.

Results: Overall, 51,607 youth registered on the NAP (42% between 2008 and 2013). Median age was 21 (IQR 20 to 23) years; 64% were male. Overall ART initiation was 80% in the first period and 83% in the second. The ART initiation rate was higher among YLHIV aged 15 to 19 years (86%) than 20 to 24 years (82%) (p < 0.001) in the second period. The proportion of youth starting rapid ART increased significantly from 27% to 52% between the two periods (p < 0.001). Factors associated with ART initiation were age 15 to 19 years (aSHR 1.09, 95% CI 1.06 to 1.11), female (aSHR 1.26, 95% CI 1.23 to 1.29) and registration year 2014 to 2018 (aSHR 1.73, 95% CI 1.69 to 1.76). The cumulative incidence of LTFU/death prior to ART initiation at 12 months was 3.8% (95% CI 3.6% to 4.1%) in the first period and 1.9% (95% CI 1.8% to 2.1%) in the second period.

Conclusions: In the era of universal treatment of all at any CD4 level, 83% of YLHIV registered on the Thai National AIDS Program initiated ART. The majority initiated within one month of registration.
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http://dx.doi.org/10.1002/jia2.25574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459169PMC
September 2020

Youth-friendly services and a mobile phone application to promote adherence to pre-exposure prophylaxis among adolescent men who have sex with men and transgender women at-risk for HIV in Thailand: a randomized control trial.

J Int AIDS Soc 2020 09;23 Suppl 5:e25564

Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Introduction: Strategies are needed to curb the increasing HIV incidence in young men who have sex with men (YMSM) and transgender women (YTGW) worldwide. We assessed the impact of youth-friendly services (YFS) and a mobile phone application (app) on adherence to pre-exposure prophylaxis (PrEP) in YMSM and YTGW in Thailand.

Methods: A randomized control trial was conducted in YMSM and YTGW aged 15 to 19 years. Participants were provided daily oral tenofovir disoproxil fumerate/emtricitabine (TDF/FTC), condoms and randomized to receive either YFS or YFS plus a PrEP app (YFS + APP), whose features included self-assessment of HIV acquisition risk, point rewards and reminders for PrEP and clinic appointments. Clinic visits occurred at zero, one, three and six months and telephone contact at two, four and five months. HIV testing was performed at every clinic visit. PrEP adherence was evaluated with intracellular tenofovir diphosphate (TFV-DP) concentrations in dried blood spot (DBS) samples at months 3 and 6. The primary endpoint assessed was "PrEP adherence" defined as TFV-DP DBS concentrations ≥700 fmol/punch (equivalent to ≥4 doses of TDF/week).

Results: Between March 2018 and June 2019, 489 adolescents were screened at three centres in Bangkok. Twenty-seven (6%) adolescents tested positive for HIV and 200 (41%) adolescents participated in the study. Of these, 147 were YMSM (74%) and 53 YTGW (26%). At baseline, median age was 18 years (IQR 17 to 19), 66% reported inconsistent condom use in the past month. Sexually transmitted infection prevalence was 23%. Retention at six months was 73%. In the YFS + APP arm, median app use duration was three months (IQR 1 to 5). PrEP adherence at month 3 was 51% in YFS and 54% in YFS + APP (p-value 0.64) and at month 6 was 44% in YFS and 49% in YFS + APP (p-value 0.54). No HIV seroconversions occurred during 75 person years of follow-up.

Conclusions: Youth-friendly PrEP services enabled good adherence among half of adolescent PrEP users. However, the mobile phone application tested did not provide additional PrEP adherence benefit in this randomized trial. Adolescent risk behaviours are dynamic and require adaptive programmes that focus on "prevention-effective adherence."
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http://dx.doi.org/10.1002/jia2.25564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459171PMC
September 2020

Risk factors of severe hospitalized respiratory syncytial virus infection in tertiary care center in Thailand.

Influenza Other Respir Viruses 2021 Jan 12;15(1):64-71. Epub 2020 Aug 12.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Aim: To determine factors associated with severe hospitalized Respiratory syncytial virus (RSV)-associated LRTI and to describe management in tertiary care center.

Methods: Retrospective medical record review was conducted among children under 5 years old hospitalized with RSV-associated LRTI at King Chulalongkorn Memorial Hospital. Severe RSV-associated LRTI was defined as death, mechanical ventilator, or positive pressure ventilation use, prolonged hospitalization >7 days. Factors associated with severe RSV were analyzed using univariate and multivariate logistic regression.

Results: From January 2011 to December 2016, 427 children were hospitalized. Median age was 10 months (IQR 4.2-23.0). One hundred seventy-four (41%) patients had severe RSV (11 deaths, 56 mechanical ventilators, 19 positive pressure ventilation, and 88 prolonged hospitalization). Factors associated with severe RSV were chronic lung disease (aOR 15.16 [4.26-53.91]), cirrhosis/biliary atresia (aOR 15.01 [3.21-70.32]), congenital heart disease (aOR 5.11 [1.97-13.23]), chemotherapy (aOR 4.7 [1.34-16.56]), and pre-term (aOR 2.03 [1.13-3.67]). Oxygen therapy was mainly low flow oxygen delivery. 88% of cases received bronchodilator. Parenteral antibiotics were prescribed in 37.9% of cases.

Conclusions: Children with co-morbidities have higher risk of severe RSV-associated LRTI. More than two-third of patients received bronchodilator, of which was not recommended by American Academy of Pediatrics. The specific treatment and prevention for RSV are urgently needed.
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http://dx.doi.org/10.1111/irv.12793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767956PMC
January 2021

Raltegravir use and outcomes among children and adolescents living with HIV in the IeDEA global consortium.

J Int AIDS Soc 2020 07;23(7):e25580

School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Introduction: As integrase inhibitors become available in low- and middle-income countries (LMICs), they offer the potential to expand extremely limited treatment options available to children and adolescents. In LMICs, only small numbers have used raltegravir, primarily as part of third-line regimens. Using data from the IeDEA global consortium, we aimed to describe the characteristics of children on raltegravir-containing regimens and their outcomes.

Methods: We included data from 1994 to 2017 from children (age <18 years), from East and Southern Africa, Asia and South America, who received cART regimens containing raltegravir for ≥90 days. We describe their characteristics at raltegravir start, and their immunological and virological outcomes.

Results And Discussion: In total, 62 children were included, with median age at raltegravir initiation of 14.3 years (IQR 11.2 to 15.8) and median CD4 count of 276 cells/µL (IQR 68 to 494). Among 40 (65%) with drug resistance testing prior to raltegravir, 71% were resistant to at least one protease inhibitor (PI), and 32% had high-level resistance to at least one drug class. Most (n = 50; 81%) received raltegravir as part of third-line cART following PI-based regimens, and were on regimens containing four or more drugs (n = 47, 76%). By database closure, median duration on raltegravir was 2.0 years (IQR 0.8 to 3.0), 1 (1.6%) patient had died, 6 (9.7%) were lost to follow-up and 21 (34%) had discontinued raltegravir. Among 15 patients reporting reasons for stopping raltegravir, six discontinued because it was no longer available. Within one year of starting raltegravir, among 53 patients with VL measures, 40 (75%) had VL < 1000 copies/mL, and among 54 with a reported CD4 count, 45 (83%) and 36 (67%) were ≥350 and ≥500 cells/µL, respectively, with median CD4 count increasing to 517.5 cells/µL (IQR 288 to 810).

Conclusions: Among children in LMICs, the initial use of raltegravir has been primarily for post PI-based cART. We found good virological and immunological outcomes despite frequent prior triple-class failure and high levels of drug resistance. Both access to raltegravir and long-term adherence to regimens with large pill-burdens remain challenging. Policies which promote earlier access to new drugs and simplify daily regimens for children and adolescents in LMICs are needed.
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http://dx.doi.org/10.1002/jia2.25580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387110PMC
July 2020

Identification, management and outcomes of combination antiretroviral treatment failure in adolescents with perinatal HIV infection in Asia.

Clin Infect Dis 2020 Jun 26. Epub 2020 Jun 26.

Kirby Institute, UNSW Sydney, Australia.

Background: Combination antiretroviral therapy (cART) failure is a major threat to 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 post-failure 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 3,196 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
June 2020

Continuous prophylactic ARV/ART since birth reduces seeding and persistence of the viral reservoir in vertically HIV-infected children.

Clin Infect Dis 2020 Jun 5. Epub 2020 Jun 5.

Centre de Recherche du CHUM and department of microbiology, infectiology and immunology, Université de Montréal, Canada.

Background: Early antiretroviral therapy (ART) restricts the size of the HIV reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown.

Methods: We measured total and integrated HIV DNA, as well as the frequency of CD4 T-cells producing multiply-spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically-infected Thai infants. Eighty-five infants were followed longitudinally for up to three years. We compared the size of the reservoir in children who received continuous prophylactic ARV since birth versus those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings.

Results: Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous prophylactic ARV since birth compared to those in whom prophylactic ARV was discontinued or never initiated (p<0.020 and p<0.001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (<0.01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during three years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARV before starting ART and those who delayed ART initiation without receiving prior prophylaxis.

Conclusions: Neonatal prophylactic ARV with direct transition to ART durably limits the size of the HIV reservoir.
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http://dx.doi.org/10.1093/cid/ciaa718DOI Listing
June 2020

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

Husband's willingness-to-pay for HIV and syphilis screening at antenatal care clinic under the Thai universal coverage scheme.

BMC Public Health 2020 Apr 10;20(1):480. Epub 2020 Apr 10.

Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Screening for sexually transmitted infection (STI) especially HIV as early detection and treatment have been financially supported under the Thai Universal Coverage (UC) scheme since 2009 (THB140 for HIV). However, the implementation has not been evidence-based, strategic risk-based, nor economically evaluated whereas husbands who accompanied the pregnant women are likely to have a lower risk than those who did not come along. This study is aimed to determine the husband's willingness-to-pay (WTP) for his HIV and syphilis screening tests and potential factors affecting STI screenings at the antenatal care (ANC) clinic of a tertiary hospital in Thailand.

Methods: A pilot open-ended interview was conducted among 50 participants to estimate the mean and standard deviation of WTP prices for HIV and syphilis screening tests. A questionnaire was developed to obtain demographics, STI knowledge and screening history, as well as two contingent valuation methods (bidding and payment scale), using the mean WTP prices identified from the pilot study as a starting WTP with ¼SD step-up/down. The survey of 200 randomly selected husbands of pregnant women was conducted at King Chulalongkorn Memorial Hospital from April to June 2018. Descriptive statistics and logistic regression were used for data analysis.

Results: During the study period, 597 pregnant women received their first ANC. Of 368 accompanying husbands, 200 were enrolled in the study. Their median age was 31 (IQR 27-36) years old and 67% had a first child. Eighty-eight percent of the participants were willing to test for the STIs. Based on the bidding method, WTP prices for HIV and syphilis screening tests were US$14.5 (IQR 12.4-14.5) and US$9.7 (IQR 10-12), respectively. The payment scale method suggested approximately three-quarters of the WTP prices from the bidding method.

Conclusions: The husbands who accompanied their pregnant wives to the ANC clinic showed positive behaviors according to the propitious selection theory. They tend to cooperate well with STI testing and are willing to pay at least two times the price of the STI screening tests. The financial support to promote STI screenings should be reconsidered to cover other groups with higher sexual behavior risks and less WTP.
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http://dx.doi.org/10.1186/s12889-020-08613-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149847PMC
April 2020

CD4/CD8 Ratio Recovery of Children and Adolescents Living With HIV With Virological Suppression: A Prospective Cohort Study.

J Pediatric Infect Dis Soc 2021 Mar;10(2):88-96

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: There are limited data on immune restoration of young adults living with virologically suppressed human immunodeficiency virus (HIV). We investigated recovery rates of CD4/CD8 ratio among Thai children and adolescents after they initiated combination antiretroviral therapy (cART).

Methods: Children and adolescents who started cART at age of ≥ 5 years were eligible in this study if they achieved HIV RNA < 50 copies/mL and had a CD4/CD8 ratio < 0.8 at the time of virological suppression. Normalization of CD4/CD8 ratio was defined as 2 consecutive values ≥ 1. Using group-based trajectory analysis, low- and high-recovery groups were identified in terms of CD4/CD8 ratio recovery.

Results: One hundred thirty-eight children and adolescents (101 perinatally infected and 37 behaviorally infected) with median age of 10.6 years at cART treatment initiation were included. After 559 person-years of follow-up (PYFU), overall incidence rate of CD4/CD8 ratio normalization was 4.1 (95% confidence interval, 2.7-6.2) per 100 PYFU. The probabilities of normalization at 2, 5, and 10 years after HIV suppression were 5.2%, 22.6%, and 35.6%, respectively. The low-recovery group had lower median pre-cART CD4 count (146 vs 304 cells/μL, P = .01), pre-cART CD4/CD8 ratio (0.15 vs 0.23, P = .03) and at first viral suppression (0.38 vs 0.65, P = .0001), compared to the high-recovery group.

Conclusions: Less than half of children and adolescents living with HIV on cART with viral suppression had CD4/CD8 ratio normalization. Those with older age at cART initiation, lower pre-cART CD4 count, or CD4/CD8 ratio had slower ratio recovery. Long-term prognoses such as ongoing immune activation and clinical outcomes among children and adolescents on suppressive cART without CD4/CD8 ratio normalization need to be further investigated.
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http://dx.doi.org/10.1093/jpids/piaa020DOI Listing
March 2021

Greater optimisation of pharmacokinetic/pharmacodynamic parameters through a loading dose of intravenous colistin in paediatric patients.

Int J Antimicrob Agents 2020 Jun 13;55(6):105940. Epub 2020 Mar 13.

Center of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Use of colistin in children is rising in line with the increase of multidrug-resistant Gram-negative bacteria (MDR-GNB). In adults, a colistin loading dose is recommended to achieve therapeutic concentrations within 12-24 h. Here we aimed to describe the pharmacokinetic (PK) parameters of a loading dose versus a recommended initial dose of intravenous colistimethate sodium (CMS) in paediatric patients. A prospective, open-label, PK study was conducted in paediatric patients (age 2-18 years) with normal renal function. Patients (n = 20) were randomly assigned to receive either a CMS loading dose (LD group) of 4 mg of colistin base activity (CBA)/kg/dose or a standard initial dose (NLD group) of 2.5 mg (12-h interval) or 1.7 mg (8-h interval) of CBA/kg/dose. Serial blood samples were collected. Plasma concentrations of formed colistin were measured by LC-MS/MS. PK parameters were reported. Acute kidney injury (AKI) was monitored by serum creatinine and urine NGAL. The median (interquartile range) age and body weight were 8.5 (3.5-11.3) years and 21.5 (13.5-20.0) kg. The mean (standard deviation) of first-dose PK parameters of the LD group versus the NLD group were: C, 6.1 (2.4) vs. 4.1 (1.3) mg/L; AUC, 26.5 (12.5) vs. 13.5 (3.6) mg/L·h; V, 0.7 (0.4) vs. 0.6 (0.3) L/kg; and t, 2.9 (0.6) vs. 2.6 (0.4) h. No patient developed AKI by serum creatinine criteria. A CMS loading dose is beneficial for improvement of colistin exposure without increased AKI. A higher daily dose of CMS should be considered, especially for MDR-GNB treatment.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.105940DOI Listing
June 2020

Implementation of an active case management network to identify HIV-positive infants and accelerate the initiation of antiretroviral therapy, Thailand 2015 to 2018.

J Int AIDS Soc 2020 02;23(2):e25450

Bureau of AIDS, TB and STIs, Ministry of Public Health, Nonthaburi, Thailand.

Introduction: Early initiation of antiretroviral therapy (ART) can reduce HIV-related morbidity and mortality in HIV-positive infants. We implemented an Active Case Management Network to promote early ART initiation Aiming for Cure (ACC) in August 2014. We describe ACC implementation, early infant diagnosis (EID) coverage and ART initiation during August 2014 to July 2018 compared with a national EID survey during October 2007 to September 2011 (pre-ACC).

Methods: Thailand's 2014 HIV Treatment Guidelines recommend that HIV-exposed infants have HIV polymerase chain reaction (PCR) testing at birth, one month and at two to four months. Testing is done at 14 national HIV PCR laboratories. When an HIV-positive infant (HIV PCR+) is identified, PCR laboratory staff send the result to the hospital staff responsible for the infant's care and to the national laboratory case manager (CM). As part of ACC, the national laboratory CM alerts a regional CM who contacts the hospital staff caring for the infant to offer technical support with ART initiation and ART adherence. CMs enter clinical, demographic and laboratory data into the national ACC database. We analysed the ACC data from August 2014 to July 2018 to assess the ACC's impact on EID coverage, ART initiation and time-to-ART initiation.

Results: The uptake of EID increased from 64% (pre-ACC) to >95% in 2018 (ACC). The number of HIV-positive infants born declined from 429 cases (pre-ACC) to 267 cases (ACC). Median age at the first-positive PCR declined from 75 days (pre-ACC) to 60 days (ACC); P < 0.001. Among 429 infants diagnosed before ACC was started, 241 (56%) received ART; during ACC, 235 (88%) of 267 HIV-positive infants received ART. The median age at ART initiation declined from 282 days before ACC to 83 days during ACC (P < 0.001) and the median time from blood collection to ART initiation declined from 168 days before ACC to 23 days during ACC (P < 0.001).

Conclusions: An innovative case management network (ACC) has been established in Thailand and results suggest that the network is promoting EID and early ART initiation. The ACC model, using case-managed PCR notification and follow-up, may speed ART initiation in other settings.
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http://dx.doi.org/10.1002/jia2.25450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046526PMC
February 2020

Efficacy of chlorhexidine patches on central line-associated bloodstream infections in children.

Pediatr Int 2020 Jul 9;62(7):789-796. Epub 2020 Jul 9.

Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Central line-associated bloodstream infections (CLABSIs) are important hospital-acquired infections. Chlorhexidine-impregnated dressings (also known as chlorhexidine patches, CHG patches) are reported to decrease CLABSIs in adults. This study aims to determine the efficacy of CHG patches in reducing CLABSIs in children.

Methods: An open-label randomized controlled trial was conducted in children aged 2 months to 18 years, requiring a short-term catheter. Patients were randomized into two groups, allocated to receive CHG patches or standard transparent dressings. Care of the catheter was in accordance with Asia Pacific Society of Infection Control (APSIC) recommendations. Central-line-associated bloodstream infections were defined using National Healthcare Safety Network surveillance criteria.

Results: From April 2017 to April 2018, 192 children were enrolled. There were 108 CHG patch catheters and 101 standard dressing catheters, contributing to 3,113 catheter days. The median duration of catheter dwelling was 13 days, with an interquartile range (IQR) of 8-20 days. Half were placed at the jugular vein and 22% at the femoral vein. There were 23 CLABSI events. Incidence rates for CHG patches and standard dressings were 7.98 (95% confidence interval (CI), 4.25-13.65) and 6.74 (95% CI, 3.23-12.39) per 1,000 catheter days, respectively (incidence rate ratio 1.18; 95% CI, 0.52-2.70). The CLABSI pathogens were 15 Gram-negative bacteria, six Gram-positive bacteria, and two Candida organisms. Catheter colonization of CHG patches and standard dressings were 2.02 (95% CI, 0.42-5.91) and 3.07 (95% CI, 1.00-7.16) per 1,000 catheter days, respectively. Only local adverse effects occurred in 6.8% of the participants.

Conclusions: In our setting, there was no difference in CLABSI rates when the chlorhexidine patch dressings were compared with the standard transparent dressings. Strengthening of CLABSI prevention bundles is mandatory.
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http://dx.doi.org/10.1111/ped.14200DOI Listing
July 2020

Immunogenicity and safety of a 12-valent pneumococcal conjugate vaccine in infants aged 6-10 weeks: a randomized double-blind active-controlled trial.

Clin Exp Pediatr 2020 Jul 6;63(7):265-271. Epub 2019 Dec 6.

SK bioscience, Seonam-si, Republic of Korea.

Background: Pneumococcal diseases among children aged <5 years worldwide are associated with high annual mortality rates.

Purpose: This study aimed to evaluate the immunogenicity and safety of GBP411, a 12-valent pneumococcal conjugant vaccine, with a dosing schedule of 2 primary doses plus 1 booster dose (2p+1) in healthy infants.

Methods: This randomized active-controlled (Prevnar 13) double-blind phase 2 trial enrolled healthy subjects aged 6-10 weeks. Three serum concentrations of pneumococcal serotype-specific immunoglobulin G (IgG) were evaluated using the pneumococcal serotype-specific pneumonia polysaccharide enzyme-linked immunosorbent assay at 1 month after the primary doses and before and 1 month after the booster dose. The pneumococcal serotype-specific IgG titer was evaluated using a multiplex opsonophagocytic assay in a subset of 15 subjects per group.

Results: After administration of the primary doses, the proportion of subjects who achieved pneumococcal serotype-specific IgG concentrations of >0.35 μg/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P<0.001). However, after administration of the booster dose, >97% of the subjects in each group achieved IgG concentrations of ≥0.35 μg/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003).

Conclusion: The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.
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http://dx.doi.org/10.3345/cep.2019.01067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374005PMC
July 2020

Antimicrobial prescription patterns in a tertiary-care pediatric unit in Thailand.

Pediatr Int 2020 Jun 1;62(6):683-687. Epub 2020 Jun 1.

Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Antimicrobial resistance is one of the greatest public health threats worldwide. The improper prescription of antibiotics is one factor that promotes antibiotic resistance. Access to antimicrobial surveillance data is essential when assessing the pattern and appropriateness of antimicrobial prescriptions in hospitals and for the establishment of an antimicrobial stewardship program. This study aimed to describe the rate of antimicrobial use and the pattern of prescriptions in a tertiary care pediatric unit in Thailand.

Methods: A point prevalence survey on antimicrobial use was conducted monthly between January and June 2016, using standardized tools. The survey included all inpatient pediatric beds and identified all children receiving antimicrobial treatment on the day of the survey.

Results: The study included 644 children, 43.3% of whom received antimicrobial treatment during hospitalization. In general wards, the rate of antimicrobial prescriptions was 37.2%; in oncology wards it was 47.0%; in intensive care units it was 38.7%, and in surgical wards it was 67.7%. Meropenem was the most prescribed antimicrobial in the general wards (24.5%) and intensive care units (28.6%), whereas antipseudomonas was the most commonly prescribed antimicrobial in the oncology ward (26.6%). For the surgical ward, the most prescribed antimicrobial was third-generation cephalosporin for both prophylaxis and treatment (39.0%). The most common reason for antimicrobial use was the treatment of infections.

Conclusions: Nearly half of hospitalized children received at least one antimicrobial. This was comparable with other pediatric tertiary care centers, although the high use of meropenem was different. This study provides important baseline information on antimicrobial use in a large tertiary-care pediatric unit and could lead to a nationwide survey in the future.
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http://dx.doi.org/10.1111/ped.14153DOI Listing
June 2020

Pattern and Frequency of Seroreactivity to Routinely Used Serologic Tests in Early-Treated Infants With HIV.

J Acquir Immune Defic Syndr 2020 03;83(3):260-266

SEARCH, Thailand The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection.

Methods: Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies.

Results: The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 [1-4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 [0-4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay.

Conclusions: These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.
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http://dx.doi.org/10.1097/QAI.0000000000002254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050817PMC
March 2020

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

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

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

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

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

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

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

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

Gaps in the elimination of congenital syphilis in a tertiary care center in Thailand.

Pediatr Int 2020 Mar 17;62(3):330-336. Epub 2020 Mar 17.

Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn, Bangkok, Thailand.

Background: The World Health Organization has set a goal to eliminate mother-to-child transmission of syphilis to a target of <50 cases per 100 000 live births. This study aimed to determine the rate of congenital syphilis and identify gaps in prevention.

Methods: A retrospective chart review was conducted in a tertiary care center in Bangkok, Thailand. The study included all pregnant women with positive syphilis serology and their infants. All congenital syphilis cases were categorized according to Centers for Disease Control criteria.

Results: From 2013 to 2017, 69 syphilis-infected pregnant women were included, with 30 congenital syphilis cases. The rate of congenital syphilis was 115 cases (95% CI 78-164) per 100 000 live births. The median (interquartile range) maternal age was 21 (18-32) years and 12 (17%) women had human immunodeficiency virus co-infection. Regarding maternal treatment, 28 (41%) women had inadequate treatment due to 13 cases (19%) of late or no antenatal care, six cases (8%) of recent infection near delivery, five cases (7%) of failure of treatment provision, and four (6%) others. There were three syphilitic stillbirths who were prematurely born to untreated pregnant women and 67 live births (one set of twins) of which 27 met definitions of probable congenital syphilis. They received complete treatment with penicillin and had non-reactive rapid plasma reagin within the first 6 months of life, with the exception of one who had non-reactive rapid plasma reagin at the age of 7 months.

Conclusions: Congenital syphilis remains a problem in our setting. Nearly half of pregnant women who had syphilis had inadequate treatment. There is an urgent need to strengthen diagnosis and the treatment cascade of syphilis during antenatal care.
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http://dx.doi.org/10.1111/ped.14132DOI Listing
March 2020

Nonalcoholic fatty liver disease and hepatic fibrosis among perinatally HIV-monoinfected Asian adolescents receiving antiretroviral therapy.

PLoS One 2019 19;14(12):e0226375. Epub 2019 Dec 19.

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

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 RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ≥7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226375PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922447PMC
March 2020