Detection of Enteropathogens in Human Immunodeficiency Virus and Non-Human Immunodeficiency Virus-Infected Children with Acute Diarrhea in an Indonesian Tertiary Hospital Using Multiplex Real-Time Polymerase Chain Reaction.

Purpose: Diarrhea is one of the leading causes of mortality in children living in developing countries. The etiology of acute diarrhea in each healthcare center varies depending on place, time, and population. This study aimed to identify pathogen patterns in human immunodeficiency virus (HIV)-infected and non-HIV children suffering from acute diarrhea, using multiplex real time reverse transcriptase polymerase chain reaction (RT-PCR), in an Indonesian tertiary hospital. Methods: This cross-sectional study was conducted at Dr. Cipto Mangunkusumo National Hospital from March 2019 to April 2020. Results: The study showed that multiplex RT-PCR results were positive in 58.9% of the specimens, with more positive results in HIV-infected children than in non-HIV-infected children (70% vs. 54.7%). Altogether 72 enteropathogens were detected from all specimens. Enteropathogens in non-HIV children with acute diarrhea consisted of bacteria (70.6%) and viruses (29.4%) with a predominance of enteroaggregative Escherichia coli (25.4%), followed by Campylobacter spp. (11.8%), enteropathogenic E. coli (9.8%), Norovirus GII (7.8%), and Clostridium difficile (7.8%). Enteropathogens in HIV-infected children consisted of viruses (57.1%), bacteria (28.6%), and parasites (14.3%) comprising Norovirus GII (24%), Cryptosporidium spp. (14.3%), Campylobacter spp. (14.3%), Norovirus GI (14.3%), and Astrovirus (14.3%). Cryptosporidium spp. was the only parasite found in this study and was found only in HIV-infected children. In non-HIV children with acute diarrhea, most pathogens were invasive bacteria, while in HIV-infected children, more viral and parasite infections occurred, primarily caused by opportunistic pathogens. Conclusion: The pattern of enteropathogens can help clinicians determine further examinations and appropriate empirical antimicrobial therapy for the patient.

The changing characteristics of a cohort of children and adolescents living with HIV at antiretroviral therapy initiation in Asia.

Despite improvements in HIV testing and earlier antiretroviral therapy (ART) initiation in children living with HIV through the years, a considerable proportion start treatment with advanced disease. We studied characteristics of children and adolescents living with HIV and their level of immunodeficiency at ART initiation using data from a multi-country Asian cohort. We included children and adolescents who were ART-naïve and <18 years of age at ART initiation from 2011 to 2020 at 17 HIV clinics in six countries. Incidence rates of opportunistic infections (OIs) in the first two years of triple-drug ART (≥3 antiretrovirals) was also reported. Competing risk regression analysis was performed to identify factors associated with first occurrence of OI. In 2,027 children and adolescents (54% males), median age at ART initiation increased from 4.5 years in 2011-2013 to 6.7 in 2017-2020, median CD4 count doubled from 237 cells/µl to 466 cells/µl, and proportion of children who initiated ART as severely immunodeficient decreased from 70% to 45%. During follow-up, 275 (14%) children who received triple-drug ART as first treatment and had at least one clinic visit, developed at least one OI in the first two years of treatment (9.40 per 100 person-years). The incidence rate of any first OI declined from 12.52 to 7.58 per 100 person-years during 2011-2013 and 2017-2020. Lower hazard of OIs were found in those with age at first ART 2-14 years, current CD4 ≥200 cells/µl, and receiving ART between 2017 and 2020. The analysis demonstrated increasing number of children and adolescents starting ART with high CD4 count at ART start. The rate of first OI markedly decreased in children who started ART in more recent years. There remains a clear need for improvement in HIV control strategies in children, by promoting earlier diagnosis and timely treatment.

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.

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.

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.

Knowledge, Attitude, Behavior, and Socioeconomic Conditions of People Living with HIV in Indonesia During the COVID-19 Pandemic: A Cross-Sectional Study.

PURPOSE: This study aimed to analyze the knowledge, attitude, and behavior of people living with HIV (PLWH) during the COVID-19 pandemic and the pandemic's impact on their socioeconomic conditions, antiretroviral adherence, and worries. MATERIALS AND METHODS: This cross-sectional study was conducted in May-August 2020 at the Integrated HIV Center of Dr. Cipto Mangunkusumo General Hospital, Indonesia. The data were collected using an online questionnaire and an offline paper-based questionnaire. RESULTS: A total of 545 subjects participated in this study, 72.8% (397) of which were male. Most subjects were middle-aged (36-55 years old) (66.5%). Many subjects reported to have experienced reduced incomes (49.2%) or losses of income (22.4%), while 15.6% reported losing their job during the COVID-19 pandemic. Most subjects (97%) wished to continue treatment despite the many obstacles, and the subjects' knowledge about COVID-19 and its prevention was considerably good. More than 70% of subjects reported that they have been implementing the general precautions of the COVID-19 pandemic: maintaining distance, wearing a mask, washing hands, and avoiding crowds. CONCLUSION: This study provides an overview of what PLWH are experiencing, which will allow for policy-making that can help them continue their treatment with consideration of the possibility of having to live a "new normal" future.

COVID Arm After Moderna Booster in Healthcare Worker: A Case Report.

SARS CoV-2 virus has infected more than 200 million people worldwide and more than 4.4 million in Indonesia. The vaccination program has become one of the solutions launched by many countries globally, including Indonesia, to reduce the transmission rate of COVID-19. Various vaccination platforms are produced, such as inactivated, viral vector, mRNA, and protein subunit. The vaccination booster program with mRNA platform (Moderna) was launched by the Indonesian government to give better protection for health care workers, particularly from delta variant. In this case report, we discuss one of the typical side effects of Moderna vaccine, which is referred to as the COVID arm.

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.

Epidemiology, Nasopharyngeal Carriage, Serotype Prevalence, and Antibiotic Resistance of Streptococcus pneumoniae in Indonesia.

In Indonesia, pneumococcal disease represents a considerable public health concern; however, published data on the epidemiology, nasopharyngeal carriage, serotype prevalence, and antibiotic resistance of Streptococcus pneumoniae in this region are limited. Therefore, this article reviews the available data from a variety of sources and also summarizes pneumococcal conjugate vaccine implementation and recommendations in Indonesia and subsequent impact on pneumococcal disease. Regional pneumococcal vaccination recommendations in Asia were also reviewed. Studies showed that pneumococcal nasopharyngeal carriage prevalence in Indonesia was approximately 43% to 55% in healthy children aged less than 5 years, which varied by age group, region, and year. Serotype analysis of pneumococcal nasopharyngeal carriage isolates in Indonesia revealed that 38% to 60% of isolates would be covered by the 13-valent pneumococcal conjugate vaccine (PCV13). The antimicrobial resistance of pneumococcal disease has increased over time; between 1997 and 2012, resistance to penicillin and sulfamethoxazole increased from 0% to 28% and 9% to 62%, respectively. Inclusion of pneumococcal conjugate vaccines into immunization programs is being implemented gradually. In 2017, Indonesia implemented a regional PCV13 immunization program in Lombok with a 2 + 1 vaccination schedule that was expanded in 2018-2019 to West Nusa Tenggara and Bangka Belitung Provinces; this expansion is predicted to substantially reduce the burden of pneumococcal disease in Indonesia. Overall, the limited data available regarding pneumococcal disease in Indonesia highlight the unmet need for comprehensive disease surveillance studies in this region that can help direct vaccination strategies.

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.

Pregnancy Profile and Infant Outcomes Among HIV Infected Women Who Delivered in Cipto Mangunkusumo Hospital.

BACKGROUND: HIV infection in pregnancy is a big concern for the future of our nation. The virus can be transmitted to the baby through pregnancy, childbirth and during breastfeeding which rendering to early detection and intervention. The aim of this study was to describe the transmission prevention cascade among our patient. METHODS: this was a retrospective cohort study of HIV vertical transmission. The inclusion criteria was pregnant women with HIV infection who have antenatal care in Cipto Mangunkusumo Hospital from January 2013 up to December 2018. Data was retrieved from medical record, HIV registry and laboratory results. The included data were demographic, risk of infection, obstetrical data, mode of delivery, ARV history, laboratory history in mother and infant. Data was presented as descriptive. RESULTS: there was 138 HIV pregnant women included as study subjects. Most women were at 25-29 years old (39.85%), as housewife (41.30%), with history of more than one sexual partners (50.73%). The subjects was mostly multigravida (77.5%), first visit to RSCM in third trimester (98.6%), with history of antenatal care >4 times (48.6%), singleton fetus (99.3%), and delivered by C-section (84.1%). HIV diagnosis was done during pregnancy (73.53%), and already on antiretroviral (ARV) for more than 6 months (50.7%). There was 78% subjects with CD4 (24% subjects with <200 cells/mL) and 84% with viral load data (36% with viral load >200 copies/uL). Around 72.5% infants born with birth weight 2500-3500g. Almost all infant received ARV prophylaxis (97.9%) and formula feeding. PCR HIV was examined on 16 infant on 6 weeks of age and and 13 on 6 month age. There was 1 infant with viral load results >400 copies/ml which immediately refered to Pediatric HIV clinic. Bivariate analysis showed significant correlation between maternal ARV consumption and infant result at birth (P=0.05). Maternal CD4 level was not significantly correlate with neonatal virology status (P=0.12). CONCLUSION: HIV diagnosis in pregnant women is important, since ARV administration on early pregnancy significantly reduce vertical transmission. ARV prophylaxis protocols is important to prevent HIV infection on infant.

Nasopharyngeal carriage and antimicrobial susceptibility profile of Haemophilus influenzae among patients infected with HIV in Jakarta, Indonesia.

In this study, the prevalence of nasopharyngeal carriage and the antimicrobial susceptibility profile of Haemophilus influenzae were investigated in children and adults with HIV infection in Jakarta, Indonesia. Thirty-four H. influenzae isolates were identified in the children (n=16/90; 18%) and adults (n=18/200; 9%) infected with HIV. All isolates were nontypeable H. influenzae and were less susceptible to ampicillin (62%) and trimethoprim/sulfamethoxazole (41%). In this study, the H. influenzae strains carried by patients infected with HIV were dominated by non-capsulated types.

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

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.

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.

Effects of HIV Infection on Pulmonary Artery Pressure in Children.

BACKGROUND: Pulmonary hypertension may complicate human immunodeficiency virus (HIV) infection and result in right ventricular (RV) failure and premature death. There are limited data of the effects of childhood HIV infection or antiretroviral therapy (ART) on pulmonary artery pressure (PAP). OBJECTIVES: To establish if there is an association between childhood HIV infection or its treatment and pulmonary artery pressure. METHODS: The study conducted a cross-sectional study of 102 HIV-infected (48 ART-naïve, 54 ART-exposed) and 51 HIV-uninfected children in Jakarta, Indonesia, to estimate PAP using echocardiography parameters: tricuspid regurgitation peak velocity (TRV), left ventricular systolic index and diastolic eccentricity index (EI), and RV systolic function, assessed by tricuspid annulus plane systolic excursion. The association between either ART-naive or ART-exposed HIV and PAP was explored using general linear modelling adjusted for potential confounders. RESULTS: ART-exposed HIV-infected children had higher TRV (adjusted difference: 0.36 m/s; 95% confidence interval [CI]: 0.12 to 0.60; p = 0.003) and diastolic EI (adjusted difference 0.06; 95% CI: 0.01 to 0.11; p = 0.02) than did uninfected children. The EI in ART-exposed children was significantly higher than normal. ART-naive HIV-infected children had a lower tricuspid annulus plane systolic excursion (adjusted difference: -2.2 mm; 95% CI: -3.73 to -0.71; p = 0.004), despite no difference in TRV (adjusted difference: 0.18 m/s; 95% CI: -0.06 to 0.43 m/s; p = 0.14). Seven (13%) ART-exposed and 4 (8.3%) ART-naïve HIV-infected children had pulmonary hypertension. Within-HIV group comparisons showed that accounting for lower respiratory tract infections attenuated the lower RV systolic function in ART-naïve children but not in ART-exposed children (difference: -1.1 mm; 95% CI:-2.8 to 0.7 mm; p = 0.22), but not the higher left ventricular eccentricity indexes in the ART-exposed children (systolic difference: 0.07; 95% CI: 0.02 to 0.12; p = 0.007; diastolic difference: 0.08; 95% CI: 0.02 to 0.14; p = 0.006). CONCLUSIONS: ART-exposed HIV infection is associated with higher estimated PAP. Reduced RV systolic function is seen in ART-naïve HIV infection. Lower respiratory tract infection partly explains lower systolic RV function in ART-naïve relative to ART-exposed HIV infection.

The Effect of Combination of Steroid and L-Asparaginase on Hyperglycemia in Children with Acute Lymphoblastic Leukemia (ALL).

Background: Hyperglycaemia is a common side effect of steroid and L-asparaginase combinations, occurring most often during acute lymphoblastic leukemia (ALL) induction phase. To date in Indonesia, it has not been obtained data on the incidence of hyperglycemia in children with ALL in the induction phase and how the role of combinations of L-asparaginase and different type of steroid used. The purpose of this study is to determine the incidence of hyperglycemia in children ALL induction phase, knowing the difference between prednisone and dexamethasone (in combination with L-asparaginase) in causing hyperglycemia in children with ALL and determine the relationship of other factors related to hyperglycaemia. Methods: This was a prospective analytic study with a pre- and post-test design, conducted in three hospitals (Cipto Mangunkusumo Hospital, Dharmais Cancer Hospital, and Gatot Soebroto Hospital). Patient's blood glucose levels (BGL) were checked at the 3rd (pretest), 4th, 5th and 6th week of protocol (post-test). Result: Of the 57 patients, 5.2% had hyperglycemia. The patients' age ranged from 1.4 years old to 15.8 years old (6.7 years old). There was no relationship between age, central nervous system (CNS) infiltration, leukocytosis, Down syndrome, nutritional status, family history of diabetes, infections and ALL stratification with hyperglycemia (p>0.05). Dexamethasone has more chance of obtaining higher mean rate of change in BGL compared to prednisone. (p < 0.05; RR 10.68; CI 95% 1.52-74.73). Conclusion: The incidence of hyperglycemia in this study is 5.2%. Dexamethasone, in combination with L-asparaginase, despite having no difference in causing hyperglycemia, has an increased risk of changing BGL compared to prednisone.

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.

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

BACKGROUND: Perinatally HIV-infected adolescents (PHIVA) are exposed to a chronic systemic infection and long-term antiretroviral therapy (ART), leaving them susceptible to morbidities associated with inflammation, immunodeficiency and drug toxicity. METHODS: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria. RESULTS: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years. CONCLUSIONS: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.

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

BACKGROUND: Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving. SETTING: An Asian cohort in 16 pediatric HIV services across 6 countries. METHODS: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA ≥1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA ≥1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure. RESULTS: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure. CONCLUSIONS: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required.

Seroprevalence of Hepatitis B Among HIV-infected Children and Adolescents Receiving Antiretroviral Therapy in the TREAT Asia Pediatric HIV Observational Database.

BACKGROUND: Hepatitis B (HBV)-HIV coinfection is associated with liver inflammation, which can progress to liver fibrosis/cirrhosis and hepatocellular carcinoma. We determined HBV seroprevalence in children and adolescents participating in the TREAT Asia Pediatric HIV Observational Database. METHODS: A multisite cross-sectional study was conducted in HIV-infected patients currently <25 years old receiving antiretroviral treatment (ART) who had HBV surface antigen (HBsAg), or HBV surface antibody (anti-HBs) or HBV core antibody (anti-HBc) tested during 2012-2013. HBV coinfection was defined as having either a positive HBsAg test or being anti-HBc positive and anti-HBs negative, reflective of past HBV infection. HBV seroprotection was defined as having a positive anti-HBs test. RESULTS: A total of 3380 patients from 6 countries (Vietnam, Thailand, Cambodia, Malaysia, Indonesia and India) were included. The current median (interquartile range) age was 11.2 (7.8-15.1) years. Of the 2755 patients (81.5%) with HBsAg testing, 130 (4.7%) were positive. Of 1558 (46%) with anti-HBc testing, 77 (4.9%) were positive. Thirteen of 1037 patients with all 3 tests were anti-HBc positive and HBsAg and anti-HBs negative. One child was positive for anti-HBc and negative for anti-HBs but did not have HBsAg tested. The prevalence of HBV coinfection was 144/2759 (5.2%) (95% confidence interval: 4.4-6.1). Of 1093 patients (32%) with anti-HBs testing, 257 (23.5%; confidence interval: 21.0-26.0) had positive tests representing HBV seroprotection. CONCLUSIONS: The estimated prevalence of HBV coinfection in this cohort of Asian HIV-infected children and adolescents on ART was 5.2%. The majority of children and adolescents tested in this cohort (76.5%) did not have protective HBV antibody. The finding supports HBV screening of HIV-infected children and adolescents to guide revaccination, the use of ART with anti-HBV activity and future monitoring.