Background We determined the prevalence and incidence of liver dysfunction prior to and after initiation of combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database (TApHOD). Methods Data from children initiated on cART between 2–18 years of age with baseline alanine aminotransferase (ALT) available prior to and at least once after cART initiation in TApHOD between 2008–2012 were analyzed. Prevalence and incidence of liver dysfunction, and biomarkers including the aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB4 index were assessed. Results Data from 1930 children were included. Their median age was 6.9 years; 49% were male; 98% were perinatally infected; and 94% were initiated on non-nucleoside reverse transcriptase-based cART regimens. Prior to cART, the prevalence of ALT ≥ 3 times the upper limit of normal (*ULN) was 5.8%. There were 8.5% of children with APRI >1.5 (suggestive of liver fibrosis), and 2.7% with FIB4 index >1.3 (predictive of possible cirrhosis). Among the 1143 cases with normal baseline ALT (≤1*ULN), the incidence of ALT 3*ULN after cART was 1.19/1000 person-months (95% CI 0.93–1.51). Two of 350 with available tests (0.6%) met Hy’s law (ALT >3*ULN and total bilirubin >2*ULN). By multivariate analysis, baseline hemoglobin <7.5 g/dL was a predictor of ALT >3*ULN, while age 5–9 years at cART initiation was protective for liver dysfunction. Conclusions We demonstrated a low prevalence and incidence of liver dysfunction before and after cART initiation in children with normal baseline chemistries. In this population facing life-long cART, prospective surveillance for emergence of liver disease is warranted.

Background Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population. Methods Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or BMI-for-age z-score <−3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age z-score <−3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification. Results Three hundred fifty five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age z-score increased from −5.6 at ART initiation to −2.3 after 36 months. Not using cotrimoxazole prophylaxis at baseline was associated with poor weight recovery (OR 2.49 vs. using, 95%CI 1.66-3.74, p<0.001). Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (OR 1.78 for z-score <−4.5 vs. −3.5 to <−3.0, 95%CI 1.08-2.92, p=0.023) and mortality (HR 2.57 for z-score <−4.5 vs. −3.5 to <−3.0, 95%CI 1.24-5.33, p=0.011). Twenty two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years and rates did not differ by malnutrition severity. Discussion Cotrimoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability but CD4% response is compromised in children with a very low weight-for-height/BMI-for-age z-score which may contribute to their high rate of mortality.

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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.

Regular CD4 testing may be unnecessary for virally suppressed children aged 5-15 years with CD4 ≥500 cells/mm3.

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.

Introduction Recommendations on the optimal frequency of plasma viral load ( pVL ) monitoring in children living with HIV ( CLWH ) who are stable on combination antiretroviral therapy ( cART ) are inconsistent. This study aimed to determine the impact of annual versus semi‐annual pVL monitoring on treatment outcomes in Asian CLWH. Methods Data on children with perinatally acquired HIV aged <18 years on first‐line, non‐nucleoside reverse transcriptase inhibitor‐based cART with viral suppression (two consecutive pVL <400 copies/ mL over a six‐month period) were included from a regional cohort study; those exposed to prior mono‐ or dual antiretroviral treatment were excluded. Frequency of pVL monitoring was determined at the site‐level based on the median rate of pVL measurement: annual 0.75 to 1.5, and semi‐annual >1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000 copies/ mL ), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL <400 copies/ mL . Competing risk regression models were used to identify predictors of treatment failure. Results During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi‐annual pVL monitoring (n = 4) respectively. Pre‐ cART , 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD 4 percentage was 9%, and the median pVL was 5.2 log 10 copies/ mL . At baseline, the median age was 9.2 years, 64% were on nevirapine‐based regimens, the median cART duration was 1.6 years, and the median CD 4 percentage was 26%. Over the follow‐up period, 258 (25%) CLWH with annual and 40 (23%) with semi‐annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI : 4.8 to 6.1) and 4.3 (95% CI : 3.1 to 5.8) per 100 patient‐years of follow‐up respectively ( p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12...

Purpose.The epidemiology of melioidosis in Vietnam, a disease caused by the soil bacterium Burkholderia pseudomallei, remains unclear. This study aimed to detect pediatric melioidosis in South Vietnam and describe clinical features and the geographical distribution. Methods. We introduced a simple laboratory algorithm for detecting B. pseudomallei from clinical samples at Children’s Hospital 2 in Ho Chi Minh City in July 2015. B. pseudomallei culture isolates were confirmed by molecular methods. A retrospective observational study of children aged < 16 years with culture-confirmed melioidosis between July 2015 and August 2019 was undertaken. Results.Thirty-five pediatric cases of melioidosis were detected, with cases originating from 13 out of 32 provinces and cities in South Vietnam. The number of pediatric melioidosis cases detected from a certain region correlated with the overall number of inpatients originating from the respective geographical area. Suppurative parotitis (n = 15; 42.8 %) was the most common clinical presentation, followed by lung infection (n = 10; 28.6 %) and septicemia (n = 7; 20 %). Fourteen (40 %) children had disseminated disease, including all cases of lung infection. Four (11.4 %) deaths occurred in the disseminated disease group. Conclusions. We report here the first series of pediatric cases of melioidosis from Vietnam detected in a single big referral children’s hospital in Ho Chi Minh City. The patients’ origin indicates a wide distribution of melioidosis in South Vietnam. It seems probably that cases not only in children but also in adults remain grossly undiagnosed. Further awareness raising and laboratory capacity strengthening are needed in this part of the country.