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BackgroundP1093 is an ongoing phase I/II multicenter open-label study of dolutegravir plus an optimized background regimen in age-defined pediatric cohorts; here we report the long-term safety and virologic efficacy outcomes for the oldest cohort.MethodsThe study enrolled human immunodeficiency virus type 1 (HIV-1)-infected treatment-experienced adolescents aged 12 to

Introduction: The clinical relevance of low-level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first-line combination antiretroviral therapy (cART). Methods: CLHIV aged 14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF. Results: From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non-nucleoside reverse transcriptase inhibitor-based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow-up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person-years of follow-up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU; p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60). Conclusions: LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first-line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF. Keywords: viraemia; viral blip; viral rebound; paediatric; treatment failure; Asia, 1 | INTRODUCTION HIV plasma viral load (pVL) is an important tool to monitor treatment response and assess medication adherence in people living with HIV. One of the primary aims [...]

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 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 Results: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annua pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi-annual pVL monitoring (n = 4) respectively. Pre-cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 [log.sub.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 CD4 percentage was 26%. Over the follow-up period, 258 (25%) CLWH with annual and 40 (23%) with semi-annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient-years of follow-up respectively (p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59). Conclusions: Annual compared to semi-annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first-line NNRTI-based cART. Keywords: antiretroviral treatment; viral load; monitoring; paediatric; treatment failure; Asia, 1 INTRODUCTION In 2017, there were an estimated 1.8 million children younger than 15 years of age living with HIV (CLWH) worldwide, of whom 110,000 were in the Asia-Pacific region [...]

Neurocognitive outcome is an essential aspect of treatment for HIV-infected children. This study is aimed at assessing cognitive functioning in school-aged HIV-infected children and the change after receiving antiretroviral therapy (ART). We conducted a prospective cohort study of HIV-infected Thai children from 6-12 years of age compared with HIV-affected (children of HIV-positive mothers who were not infected with HIV), and normal control groups. Wechsler Intelligence Scale for Children-III (WISC-III) was administered at enrollment and 30 months of follow-up. Semistructured interviews of primary caregivers were performed. From April to October 2003, 121 children were enrolled; 39 HIV-infected, 40 HIV-affected, and 42 control children with a median age of 9.3 years. The HIV-infected group had a mean (standard deviation [SD]) CD4 percentage of 13.8% (5.3), 87% of whom had been receiving ART for a median of 35 weeks. At the first cognitive assessment, the mean (SD) of full-scale intelligence quotient (FSIQ) was 79 (13) and 88 (10) among HIV-infected and HIV-affected children, which was statistically lower than that of the control group at 96 (13; p < 0.01). The proportion of children with average intelligence level (FSIQ > 90) among 3 groups were 21%, 49%, and 76%, respectively (p < 0.01). At 30 months of follow-up, the HIV-infected group had a mean (SD) CD4 percentage of 25.6% (5.6); 77% had undetectable viral load. The mean (SD) FSIQ of children among three groups were 75 (12), 85 (12), and 91 (12), respectively. Compared with the baseline assessment, the verbal scale score significantly decreased in all groups, including the controls, whereas the performance scales did not change. In conclusion, school-aged HIV-infected children have lower cognitive function than HIV-affected and normal children. Cognitive function was not improved after receiving ART. Further study to address whether early ART can preserve cognitive functioning among HIV-infected children should be explored. DOI: 10.1089/apc.2009.0314

Growth failure is a common problem in HIV-infected children. The extent to which this growth failure could be reversed after the children receive antiretroviral therapy (ART) is not known. This study assessed the incidence of growth failure in HIV-infected Thai children, impact of ART on growth, and the predictors of growth reversal after initiating ART. Growth parameters and other characteristics were extracted from the database of a prospective cohort of HIV-infected children (age [less than or equal to]15 years) who were enrolled to initiate non-nucleoside reverse transcriptase inhibitor-based ART between August 2002 and May 2007. Body weight and height measurements, CD4 cell counts, plasma HIV RNA levels were collected at baseline and 24-week intervals. A total of 225 HIV-infected children were included, 116 (51%) were males. The median age at baseline was 7.4 years (interquartile range [IQR] 5.2-9.8). Fifty-three percent were in Centers for Disease Control and Prevention (CDC) category C and 54% had CD4 percentage 5 or less. The mean (standard deviation [SD]) of baseline weight-for-age (WAZ) and height-for-age (HAZ) z-scores were -2.02 (1.17) and -2.22 (1.51). The median follow-up time was 216 weeks (IQR 120-240). The cumulative probability of growth reversal among the 179 subjects with growth failure at entry was 58% (95% confidence interval [CI] 49-67) at week 240. In a multivariate Cox regression model, higher entry WAZ (p < 0.001) and HAZ (p < 0.001), use of a nevirapine-based regimen (compared to efavirenz, p = 0.027) and larger CD4% gains to week 48 (p < 0.001) were significant predictors of growth reversal after initiating ART. NNRTI-based ART leads to a substantial improvement in growth of HIV-infected children. Initiation of ART before the children developed growth failure should be encouraged. DOI: 10.1089/apc.2009.0093

Byline: Peninnah Oberdorfer, MD, PhD (Department of Pediatrics, Faculty of Medicine, Chiang Mai University, aoberdor@mail.med.cmu.ac.th); Orawan Louthrenoo, MD (Department of Pediatrics, Faculty of Medicine, Chiang Mai University); Thanyawee Puthanakit, MD [...]

Abstract Background Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. Methods A retrospective chart review was conducted at 8 Thai sites of children who switched to PI –based regimens due to failure of NNRTI –based regimens. Primary endpoints were HIV RNA Results Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p 10 copies/ml, p Conclusion Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.

Abstract Backgrounds Disseminated Penicillium marneffei infection is one of the most common HIV-related opportunistic infections in Southeast Asia. Immune reconstitution inflammatory syndrome (IRIS) is a complication related to antiretroviral therapy (ART)-induced immune restoration. The aim of this report is to present a case of HIV-infected child who developed an unmasking type of IRIS caused by disseminated P. marneffei infection after ART initiation. Case presentation A 14-year-old Thai HIV-infected girl presented with high-grade fever, multiple painful ulcerated oral lesions, generalized non-pruritic erythrematous skin papules and nodules with central umbilication, and multiple swollen, warm, and tender joints 8 weeks after ART initiation. At that time, her CD4+ cell count was 7.2% or 39 cells/mm3. On admission, her repeated CD4+ cell count was 11% or 51 cells/mm3 and her plasma HIV-RNA level was < 50 copies/mL. Her skin biopsy showed necrotizing histiocytic granuloma formation with neutrophilic infiltration in the upper and reticular dermis. Tissue sections stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Grocott methenamine silver (GMS) stain revealed numerous intracellular and extracellular, round to oval, elongated, thin-walled yeast cells with central septation. The hemoculture, bone marrow culture, and skin culture revealed no growth of fungus or bacteria. Our patient responded well to intravenous amphotericin B followed by oral itraconazole. She fully recovered after 4-month antifungal treatment without evidence of recurrence of disease. Conclusions IRIS from P. marneffei in HIV-infected people is rare. Appropriate recognition and properly treatment is important for a good prognosis.

Abstract Background Human pythiosis is an emerging and life-threatening infectious disease caused by Pythium insidiosum. It occurs primarily in tropical, subtropical and temperate areas of the world, including Thailand. The aim of this report is to present the first pediatric case of typical vascular pythiosis. Case Presentation A 10-year-old boy with underlying β-thalassemia presented with gangrenous ulcers and claudication of the right leg which were unresponsive to antibiotic therapy for 6 weeks. Computerized tomography angiography indicated chronic arterial occlusion involving the right distal external iliac artery and its branches. High-above-knee amputation was urgently done to remove infected arteries and tissues, and to stop disease progression. Antibody to P. insidiosum was detected in a serum sample by the immunoblot and the immunochromatography tests. Fungal culture followed by nucleic sequence analysis was positive for P. insidiosum in the resected iliac arterial tissue. Immunotherapeutic vaccine and antifungal agents were administered. The patient remained well and was discharged after 2 months hospitalization without recurrence of the disease. At the time of this communication he has been symptom-free for 2 years. Conclusions The child presented with the classical manifestations of vascular pythiosis as seen in adult cases. However, because pediatricians were unfamiliar with the disease, diagnosis and surgical treatment were delayed. Both early diagnosis and appropriate surgical and medical treatments are crucial for good prognosis.