Creating a data collection and management platform to support measurement of adolescent HIV care transition processes within low- and middle-income countries: The GRADUATE project.

Few national programs and research cohorts within low- and middle-income countries (LMICs) document transition-related processes and outcomes for adolescents and young adults living with HIV (AYLH) transitioning to adulthood. Between 2017-2020, The Global fRAmework of Data collection Used for Adolescent HIV Transition Evaluation (GRADUATE) project convened a collaborative advisory group to identify key variables and definitions capturing the process, predictors, and outcomes across the transition period. In total, 114 variables identified as essential to measuring AYLH transition-related data were identified and formatted into a GRADUATE Data Exchange Standard (DES), which was added to and harmonized with the existing International epidemiology Databases to Evaluate AIDS (IeDEA) DES. In 2019, the GRADUATE DES was pilot tested at four IeDEA facilities in Malawi, South Africa, and Thailand through a cross-sectional study. Upon comparing the variables to routine medical records, available data were too limited to adequately capture transition-related processes and outcomes. However, additional data collection using GRADUATE tools was feasible and improved completeness. Of the 100 (52% female) AYLH included in the pilot study, 71% had transitioned/transferred to adult care, with 42% transitioning from an adolescent-specific model of care within an integrated family clinic to having their clinic visits scheduled on a different day of the week while 58% transferred from a pediatric facility to one offering adult HIV care. While almost all (94%) had a transition-related discussion with their healthcare providers prior to the transition, we found that 69% (95% CI 49-85%) were somewhat or very satisfied/comfortable with the post-transfer clinic and the staff. Utilization of the GRADUATE DES better characterized AYLH transitioning to adulthood across LMICs, and optimally measured transition preparation activities and outcomes. Utilization of the GRADUATE DES in other settings could facilitate comparisons and identify gaps in the care of transitioning adolescents that need to be addressed.

High mortality in adolescents and young adults with perinatally-acquired HIV in Thailand during the transition to adulthood.

Transitioning from pediatric to adult care remains a challenge for adolescents and young adults with perinatally-acquired HIV (AYA-PHIV). We assessed treatment outcomes and mortality among Thai AYA-PHIV. The study included AYA-PHIV who reached age 18-24 years who started antiretroviral treatment during childhood at five pediatric HIV clinics across Thailand. From November 2020-July 2021, data were gathered from a cohort database, medical records, and the Thai National AIDS Program. Of 811 eligible AYA-PHIV, 93% were alive; median age 22.3 years (IQR 20.6-23.7), treatment duration 16.1 years (IQR 13.4-18.0). Current HIV care was provided in adults (71%) and pediatric clinics (29%). Treatment regimens included non-nucleoside reverse transcriptase inhibitors (55%), protease inhibitors (36%), and integrase inhibitors (8%); 78% had HIV RNA <200 copies/ml. Of the 7.0% who died, median age at death was 20.8 years (IQR 20.6-22.1); 88% were AIDS-related death. Mortality after age 18 was 1.76 per 100-person years (95% confidence interval 1.36-2.28). Those with CD4 <200 cell/mm3 at age 15 had higher risk of mortality (adjusted hazard ratio 6.16, 95% CI 2.37-16.02). In conclusion, the high mortality among Thai AYA-PHIV indicated the need for better systems to support AYA-PHIV during the transition to adulthood.

Case Report: Melioidosis-Related Severe Cutaneous Features of Erythema Nodosum in a Thai Child.

Erythema nodosum (EN) is characterized by rapidly developing, painful, erythematous subcutaneous nodules, most of which are located in the pretibial areas. This cutaneous finding can be caused by a variety of conditions, however Burkholderia pseudomallei is rarely the cause. This particular patient presented with a high-grade fever with characteristic EN on both pretibial areas. All of the typical EN causes were investigated, but the findings were all negative. The lesions progressed to severe hemorrhagic bleb features, and because the patient resided in Northeast Thailand, a melioidosis-endemic region, testing for B. pseudomallei was performed. Because a high level of melioidosis serology of more than 1:10,240 was detected, melioidosis therapy was started. At the 12-week follow-up after melioidosis therapy, the titer had declined to 1:1,280, indicating that melioidosis-related severe, cutaneous EN symptoms were the most likely diagnosis in this patient. We discovered a case of EN with severe hemorrhagic bleb features as a unique clinical manifestation of melioidosis. When a patient resides in an endemic area, B. pseudomallei should always be considered as a possible causative organism.

Effectiveness of a Mobile App (KhunLook) Versus the Maternal and Child Health Handbook on Thai Parents' Health Literacy, Accuracy of Health Assessments, and Convenience of Use: Randomized Controlled Trial.

BACKGROUND: Children of parents who have higher health literacy (HL) benefit more from preventive child health care. Digital interventions have been used to improve parents' HL with high satisfaction. KhunLook is a Thai mobile app conceived using strategies to improve HL. It was developed to assist parents in assessing and keeping track of their child's health in complement to the standard Maternal and Child Health Handbook (MCHH). OBJECTIVE: This trial focuses on the effectiveness of using the KhunLook app with the MCHH and standard care (intervention) compared with the conventional MCHH and standard care (control) on parents' HL. Data on accuracy of parents' assessment of their child's health and growth as well as convenience of use of the tool (app or MCHH) in the well-child clinic were collected at 2 visits (immediate=visit 1, and intermediate=visit 2). METHODS: Parents of children under 3 years of age who (1) had a smartphone or tablet and the MCHH and (2) could participate in 2 visits, 2-6 months apart at Srinagarind Hospital, Khon Kaen, Thailand, were enrolled in this 2-arm parallel randomized controlled trial between April 2020 and May 2021. Parents were randomized 1:1 to 2 groups. At visit 1, data on demographics and baseline HL (Thailand Health Literacy Scales) were collected. Parents in the app group used the KhunLook app and the control group used their child's handbook to assess their child's growth, development, nutrition and feeding, immunization status and rated the convenience of the tool they used. At visit 2, they repeated the assessments and completed the HL questionnaire. RESULTS: A total of 358 parents completed the study (358/408, 87.7%). After the intervention, the number of parents with high total HL significantly increased from 94/182 (51.6%) to 109/182 (59.9%; 15/182; Δ 8.2%; P=.04), specifically in the health management (30/182; Δ 16.4%; P<.001) and child health management (18/182; Δ 9.9%; P=.01) domains in the app group, but not in the control group. Parents in the app group could correctly assess their child's head circumference (172/182, 94.5% vs 124/176, 70.5%; P<.001) and development (173/182, 95.1% vs 139/176, 79.0%; P<.001) better than those in the control group at both visits. A higher proportion of parents in the app group rated their tool as very easy or easy to use (174-181/182, 95.6%-99.5% vs 141-166/176, 80.1%-94.3%; P<.001) on every item since the first visit. CONCLUSIONS: Our results suggest the potential of a smartphone app (KhunLook) to improve parents' HL as well as to promote superior accuracy of parents' assessment of their child's head circumference and development, with a similar effect on weight, height, nutrition and feeding, and immunization as in traditional interventions. Using the KhunLook app is useful and more convenient for parents in promoting a healthy child preventive care during early childhood. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20200312003; https://www.thaiclinicaltrials.org/show/TCTR20200312003.

Lipid and glucose abnormalities and associated factors among children living with HIV in Asia.

BACKGROUND: Children living with HIV (CLHIV) on prolonged antiretroviral therapy (ART) are at risk for lipid and glucose abnormalities. Prevalence and associated factors were assessed in a multicentre, Asian longitudinal paediatric cohort. METHODS: CLHIV were considered to have lipid or glucose abnormalities if they had total cholesterol ≥200 mg/dL, high-density lipoprotein (HDL) ≤35 mg/dL, low-density lipoprotein (LDL) ≥100 mg/dL, triglycerides (TG) ≥110 mg/dL, or fasting glucose >110 mg/dL. Factors associated with lipid and glucose abnormalities were assessed by logistic regression. RESULTS: Of 951 CLHIV, 52% were male with a median age of 8.0 (interquartile range [IQR] 5.0-12.0) years at ART start and 15.0 (IQR 12.0-18.0) years at their last clinic visit. 89% acquired HIV perinatally, and 30% had ever used protease inhibitors (PIs). Overall, 225 (24%) had hypercholesterolemia, 105 (27%) low HDL, 213 (58%) high LDL, 369 (54%) hypertriglyceridemia, and 130 (17%) hyperglycemia. Hypercholesterolemia was more likely among females (versus males, aOR 1.93, 95% CI 1.40-2.67). Current PIs use was associated with hypercholesterolemia (current use: aOR 1.54, 95% CI 1.09-2.20); low HDL (current use: aOR 3.16, 95% CI 1.94-5.15; prior use: aOR 10.55, 95% CI 2.53-43.95); hypertriglyceridemia (current use: aOR 3.90, 95% CI 2.65-5.74; prior use: aOR 2.89, 95% CI 1.31-6.39); high LDL (current use: aOR 1.74, 95% CI 1.09-2.76); and hyperglycemia (prior use: aOR 2.43, 95% CI 1.42-4.18). CONCLUSION: More than half and one-fifth of CLHIV have dyslipidemia and hyperglycemia, respectively. Routine paediatric HIV care should include metabolic monitoring. The association between PIs use and dyslipidemia emphasizes the importance of rapidly transitioning to integrase inhibitor-containing regimens.

Global HIV prevention, care and treatment services for children: a cross-sectional survey from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

OBJECTIVES: To assess access children with HIV have to comprehensive HIV care services, to longitudinally evaluate the implementation and scale-up of services, and to use site services and clinical cohort data to explore whether access to these services influences retention in care. METHODS: A cross-sectional standardised survey was completed in 2014-2015 by sites providing paediatric HIV care across regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We developed a comprehensiveness score based on the WHO's nine categories of essential services to categorise sites as 'low' (0-5), 'medium', (6-7) or 'high' (8-9). When available, comprehensiveness scores were compared with scores from a 2009 survey. We used patient-level data with site services to investigate the relationship between the comprehensiveness of services and retention. RESULTS: Survey data from 174 IeDEA sites in 32 countries were analysed. Of the WHO essential services, sites were most likely to offer antiretroviral therapy (ART) provision and counselling (n=173; 99%), co-trimoxazole prophylaxis (168; 97%), prevention of perinatal transmission services (167; 96%), outreach for patient engagement and follow-up (166; 95%), CD4 cell count testing (126; 88%), tuberculosis screening (151; 87%) and select immunisation services (126; 72%). Sites were less likely to offer nutrition/food support (97; 56%), viral load testing (99; 69%) and HIV counselling and testing (69; 40%). 10% of sites rated 'low', 59% 'medium' and 31% 'high' in the comprehensiveness score. The mean comprehensiveness of services score increased significantly from 5.6 in 2009 to 7.3 in 2014 (p<0.001; n=30). Patient-level analysis of lost to follow-up after ART initiation estimated the hazard was highest in sites rated 'low' and lowest in sites rated 'high'. CONCLUSION: This global assessment suggests the potential care impact of scaling-up and sustaining comprehensive paediatric HIV services. Meeting recommendations for comprehensive HIV services should remain a global priority.

Disclosure of HIV status and associated clinical outcomes of children and adolescents living with HIV in Asia.

Disclosure of HIV status is an important part of pediatric care. We studied disclosure and clinical outcomes in a multi-country Asian cohort of children and adolescents with HIV. Those 6-19 years of age who initiated combination antiretroviral therapy (cART) between 2008 and 2018, and who had at least one follow-up clinic visit were included. Data up to December 2019 were analyzed. Cox and competing risk regression analyses were used to assess the effect of disclosure on disease progression (WHO clinical stage 3 or 4), loss to follow-up (LTFU; > 12 months), and death. Of 1913 children and adolescents (48% female; median [IQR] age 11.5 [9.2-14.7] years at last clinic visit), 795 (42%) were disclosed to about their HIV status at a median age of 12.9 years (IQR: 11.8-14.1). During follow-up, 207 (11%) experienced disease progression, 75 (3.9%) were LTFU, and 59 (3.1%) died. There were lower hazards of disease progression (adjusted hazard ratio [aHR] 0.43 [0.28-0.66]) and death (aHR 0.36 [0.17-0.79]) for those disclosed to compared with those who were not. Disclosure and its appropriate implementation should be promoted in pediatric HIV clinics in resource-limited settings.

Alcohol use, suicidality and virologic non-suppression among young adults with perinatally acquired HIV in Thailand: a cross-sectional study.

INTRODUCTION: Young adults with perinatally acquired HIV (YA-PHIV) are facing transitions to adult life. This study assessed health risk behaviours (including substance use), mental health, quality of life (QOL) and HIV treatment outcomes of Thai YA-PHIV. METHODS: A cross-sectional study was conducted in Thai YA-PHIV aged 18-25 years who were enrolled in a prospective cohort study at five tertiary paediatric HIV care centres in Thailand. Study data were obtained through face-to-face interviews from November 2020 to July 2021. Assessments were performed for alcohol use (Alcohol Use Disorders Identification Test; AUDIT), smoking (Fagerstrom Test for Nicotine Dependence), drug/substance use (Drug Abuse Screening Test; DAST-10), depression (Patient Health Questionnaire for Adolescents; PHQ-A), anxiety (Generalized Anxiety Disorder; GAD-7) and QOL (World Health Organization QOL Brief-Thai). HIV treatment outcomes were extracted from the National AIDS Program database. RESULTS: Of 355 YA-PHIV, 163 (46%) were males: their median age was 21.7 (interquartile range, IQR 20.2-23.5) years. There were 203 YA-PHIV (58%) who reported ever having sex; 141 (40%) were sexually active in the past 6 months, of whom 86 (61%) reported 100% condom use. Overall, 49 (14%) met the criteria for harmful alcohol use; 28 (7.9%) were alcohol dependent. Sixty (17%) were current smokers and 37 (11%) used drugs/substances. The frequency of moderate up to severe symptoms for depression was 18% and for anxiety was 9.7%. Their overall QOL was good in 180 (51%), moderate in 168 (47%) and poor in five (1.4%). There were 49 YA-PHIV (14%) with CD4 <200 cells/mm3 and 85 (24%) with virologic non-suppression (HIV-RNA >200 copies/ml). On multivariate analyses, the highest education at the primary to high school or vocational school levels (adjusted odds ratio [aOR] 2.02, 95% CI 1.40-3.95, p 0.04), harmful alcohol use (aOR 2.48, 95% CI 1.24-4.99, p 0.01), alcohol dependence (aOR 3.54, 95% CI 1.51-8.31, p <0.01) and lifetime suicidal attempt (aOR 2.66, 95% CI 1.11-6.35, p 0.03) were associated with non-suppression. CONCLUSIONS: Regular screening for alcohol use and mental health, including suicidality, would be useful to identify YA-PHIV who need more intensive psychosocial support or referral services to ensure they can achieve and maintain a high QOL into adult life.

Long-Term Post-Transition Outcomes of Adolescents and Young Adults Living With Perinatally and Non-perinatally Acquired HIV in Southeast Asia.

PURPOSE: We assessed factors associated with clinical, social, and behavioral outcomes of adolescents and young adults with HIV (AYHIV) in Southeast Asia after transition from pediatric to adult HIV care. METHODS: AYHIV in Malaysia, Thailand, and Vietnam were prospectively followed through annual clinical assessments and laboratory testing. Data were described descriptively and a generalized estimating equation was used to calculate independent predictors for HIV viremia (>40 copies/mL). RESULTS: A total of 93 AYHIV were followed until February 2019: 60% female, 94% acquired HIV perinatally, 81% Thai, median age 20 (interquartile range, 18-21) years. The median follow-up time was 94 (91-100) weeks; 88% completed the study. At week 96, median CD4 was 557 cells/mm3 (interquartile range, 337-786), 77% had suppressed HIV viral load, 39% reported recent alcohol use, 49% had been sexually active, 53% of females and 36% of males intended to have children, and 23% screened positive for moderate depression (Patient Health Questionnaire-9 score ≥9) or reported suicidal ideation. HIV viremia was associated with <90% adherence to HIV treatment (adjusted incidence rate ratio [aIRR] 2.2 [1.28-3.78]), CD4 count ≤500 cells/mm3 (aIRR 4.75 [2.11-10.69]), and being on a nonnucleoside reverse transcriptase inhibitor regimen (vs. protease inhibitor aIRR 2.71 [1.13-6.49]). Having a trusted person to talk with about their feelings was protective (vs. never; usually or always, aIRR 0.41 [0.18-0.92]). DISCUSSION: After transition to adult HIV care, there were indications of social isolation and mental health problems that could prevent these AYHIV from maintaining control over their HIV infection and hinder progress toward social independence.

Pregnancy and birth outcomes among young women living with perinatally acquired HIV in Thailand and Vietnam.

We conducted a retrospective cohort study of pregnancy and infant outcomes in 670 adolescents and young adult women with perinatally acquired HIV (AYAPHIV), aged 15-24 years, in Thailand and Vietnam. Between January 2013 and December 2018, there were 52 pregnancies, for an incidence of 2.49 (95% CI 1.90-3.27) per 100 person-years. The median age at pregnancy was 17.7 years (IQR 16.8-18.9). Pregnant AYAPHIV had been on cART for a lifetime median of 9.8 years (IQR 7.3-12.4). At the time of conception, the median CD4 was 521 cells/mm3 (IQR 213-760), and 76% had HIV RNA ≤400 copies/ml. Of the 51 pregnancies with available outcomes, 90% resulted in live singleton births at a median gestational age of 38 weeks (IQR 37-39); 77% of mothers (n = 27/35) had HIV RNA ≤400 copies/ml at delivery. Among infants with available data, 50% (n = 21/42) were male and 29% (n = 12/42) were reported to be low birthweight (<2,500gm); none (n = 0/41) were breastfed. One infant was diagnosed with HIV. Our findings emphasize that efforts to strengthen reproductive health education, including contraception, pregnancy-related psychosocial support services, and prevention of vertical HIV transmission interventions, in our region are needed for adolescents with perinatally acquired HIV as they transition to young adults.

Mortality and Comorbidities in Extremely Low Birth Weight Thai Infants: A Nationwide Data Analysis.

This is the first nationwide study aimed to evaluate in-hospital mortality and comorbidities of extremely low birth weight (ELBW) infants in Thailand between 2015-2020. Data of ELBW infants were collected from the National Health Coverage Scheme. The incidence of ELBW Thai infants was 1.75 per 1000 live births. Sixty-five percent of ELBW infants were delivered in tertiary-care facilities, with 63% surviving until discharge. In-hospital mortality was 36.9%. Non-invasive respiratory supports were documented in just 17.6% of the study population, whereas total parenteral nutrition was used in 52.3% of neonates. There were several comorbidities, with the three most frequent including respiratory distress syndrome (70.7%), neonatal jaundice (66.7%), and sepsis (60.4%). The median hospitalization cost for one ELBW infant who survived was 296,438.40 baht ($8719). Conclusion: Thailand had an acceptable ELBW infant survival rate (63%), but comorbidities remained particularly severe and cost one hundred times the median hospital cost for one ELBW infant that survived in comparison to a normal newborn infant. Better health outcomes require strategies to raise awareness of the issues and the appropriate implementation of evidence-based solutions, particularly improving neonatal care facilities, as well as early referral of high-risk pregnant women and neonates, which will aid in the future reduction of neonatal morbidities and mortalities.

Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand.

BACKGROUND: Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. METHODS: Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit. RESULTS: 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months (n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (n=83) was 147 [16, 267] cells/mm3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. CONCLUSION: Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.

Early-onset neonatal sepsis and antibiotic use in Indonesia: a descriptive, cross-sectional study.

BACKGROUND: Early diagnosis and prompt antibiotic treatment are crucial to reducing morbidity and mortality of early-onset sepsis (EOS) in neonates. However, this strategy remains challenging due to non-specific clinical findings and limited facilities. Inappropriate antibiotics use is associated with ineffective therapy and adverse outcomes. This study aims to determine the characteristics of EOS and use of antibiotics in the neonatal-intensive care units (NICUs) in Indonesia, informing efforts to drive improvements in the prevention, diagnosis, and treatment of EOS. METHODS: A descriptive study was conducted based on pre-intervention data of the South East Asia-Using Research for Change in Hospital-acquired Infection in Neonates project. Our study population consisted of neonates admitted within 72 h of life to the three participating NICUs. Neonates who presented with three or more clinical signs or laboratory results consistent with sepsis and who received antibiotics for 5 consecutive days were considered to have EOS. Culture-proven EOS was defined as positive blood or cerebrospinal fluid culture. Type and duration of antibiotics used were also documented. RESULTS: Of 2,509 neonates, 242 cases were suspected of having EOS (9.6%) with culture-proven sepsis in 83 cases (5.0% of neonatal admissions in hospitals with culture facilities). The causative organisms were mostly gram-negative bacteria (85/94; 90.4%). Ampicillin / amoxicillin and amikacin were the most frequently prescribed antibiotics in hospitals with culture facilities, while a third-generation cephalosporin was mostly administered in hospital without culture facilities. The median durations of antibiotic therapy were 19 and 9 days in culture-proven and culture-negative EOS groups, respectively. CONCLUSIONS: The overall incidence of EOS and culture-proven EOS was high in Indonesia, with diverse and prolonged use of antibiotics. Prospective antibiotic surveillance and stewardship interventions are required.

Severe Recurrent Bacterial Pneumonia Among Children Living With HIV.

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.

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

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.

A Mobile App, KhunLook, to Support Thai Parents and Caregivers With Child Health Supervision: Development, Validation, and Acceptability Study.

BACKGROUND: In Thailand, children born in government hospitals receive a maternal and child health handbook (MCHH). However, when a new MCHH edition is released, those with the previous editions do not have access to the updated information. A mobile app is an appealing platform to fill this gap. We developed a mobile app called "KhunLook" as an interactive electronic MCHH intended to assist parents in child health supervision. OBJECTIVE: This study describes the user requirements and development of the KhunLook mobile app, validity of parents' growth assessments, and parents' evaluation of feasibility and acceptability of the app. METHODS: Phase 1 was a qualitative study using individual interviews. The interview data were used to revise the prototype. In phase 2, parents were randomly assigned to assess their children's growth with the app or the MCHH. The outcomes were compared to those of the physician's assessment, and congruence was determined. In phase 3, parents evaluated the feasibility and acceptability of the app in comparison to the MCHH through a web-based survey. RESULTS: Four health care providers and 8 parents participated in phase 1. Two themes were identified: (1) the mobile app potentially counters parents' infrequent use of the MCHH with accuracy, attractiveness, convenience, and simplicity, and (2) health supervision needs to be standard, up-to-date, and understandable. KhunLook was publicly launched with a family page and 7 key features: growth and nutrition, development, immunizations, oral health, reminders for the next appointment, memories, and health advice. In phase 2, 56 parents participated in the growth parameter assessments; 34 were in the App group and 22 in the MCHH group. The outcomes of the growth parameter assessments between parents and physicians in both the App and MCHH groups were not significantly different. The congruence proportions were higher in the App group for weight and head circumference, but the differences were not statistically significant. In phase 3, 356 parents from all over Thailand participated in a web-based survey. Parents rated the app feasibility as "very easy to easy" to use at higher proportions than the MCHH in all health assessment domains (growth, development, and immunizations) and ease-of-use domains with statistical significance (P<.001). The KhunLook app received a significantly higher mean score (8.59/10) than the MCHH (7.6/10) (P<.001). Most parents (317/356, 89.0%) preferred the app over MCHH. Further, 93.5% (333/356) of the parents stated that they would continue to use the app and 96.9% (345/356) would recommend others to use it. CONCLUSIONS: KhunLook, a Thai mobile app for child health supervision, was developed, validated for growth assessments, and was well accepted for ease-of-use by parents. Further studies should be conducted with a large scale of users, and the impact of this app on health behaviors and health outcomes must be evaluated.

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

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.

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

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/mm3 (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.

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

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.

Use and Outcomes of Antiretroviral Monotherapy and Treatment Interruption in Adolescents With Perinatal HIV Infection in Asia.

PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. METHODS: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/µL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes. CONCLUSIONS: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.