Background: There are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined the incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART. Methods: Antiretroviral (ART)-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%≥25%. IF was defined as persistent decline of ≥5% in CD4% in children with CD4%1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF. Results: 107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. Baseline data were median (IQR) age 6.2 (4.2-8.9) years, CD4% 7 (3-15), HIV-RNA 5.0 (4.9-5.5) log₁₀copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively. At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and CD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of children had immune recovery (CD4%≥25%) and 75% of children had HIV-RNA <1.7log₁₀copies/ml. Thirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in the first 24 and 48 weeks respectively. Only 1 (0.9%) child experienced IF within 96 weeks and the sensitivity (95%CI) of IF to VF was 4 (0.1-20.4)% and specificity was 100 (93.9-100)%. Conclusion: Immunologic failure, as defined here, had low sensitivity compared to VF and should not be recommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to detect early treatment failure. Trial Registration: Clinicaltrials.gov identification number NCT00476606

Dengue incidence has increased over the past few decades. One tetravalent dengue vaccine based on a yellow fever backbone has been approved, but due to increased risk of severe disease in dengue-naïve recipients, its use is limited to individuals with prior dengue exposure. We summarize the clinical development of TAK-003, a tetravalent dengue vaccine based on a live-attenuated DENV-2 backbone. We discuss vaccine development and preclinical and clinical work leading to a commercially available formulation. TAK-003 is approved in several countries and the WHO-SAGE recommend TAK-003 to be considered for public programs in high transmission areas for individuals aged 6-16 years. Finally, we discuss the potential role of TAK-003 as part of an integrated multimodal strategy for dengue prevention. TAK-003 has been assessed in a comprehensive clinical development program; demonstrating sustained efficacy and safety against all four serotypes in baseline seropositive individuals, and against DENV-1 and DENV-2 in seronegative individuals, and has been well tolerated. Effectiveness in a real world setting and safety will be monitored in ongoing and future studies, particularly for DENV-3 and DENV-4, together with the impact of a booster dose. Overall, TAK-003 shows promise as a new tool for dengue prevention.

Objectives: This study aimed to determine the prevalence of low bone mass and assess its relationship with abnormal bone turnover among HIV‐infected Asian adolescents.Methods: A multicentre, cross‐sectional study was conducted at four paediatric HIV centres in Thailand and Indonesia. Perinatally HIV‐infected adolescents aged 10–18 years receiving antiretroviral therapy (ART) with virological suppression (HIV RNA < 400 copies/mL) were enrolled. Study assessments included lumbar spine (L2−L4) dual‐energy X‐ray absorptiometry and measurement of bone turnover markers. Bone mineral density (BMD) and bone mineral apparent density (BMAD) Z‐scores were calculated based on Thai normative age‐ and sex‐matched references. Low bone mass was defined as BMD or BMAD Z‐scores ≤ −2.Results: Of 396 participants, 57% were female. The median age was 15.0 [interquartile range (IQR) 13.3–16.9] years, and 73% were in Tanner stage 3−5. At enrolment, the median CD4 T‐cell count was 734 (IQR 581–907) cells/μL, and 37% were on protease inhibitor (PI)‐based regimens. The overall prevalence of lumbar spine BMD and BMAD Z‐scores ≤ −2 were 16.4% and 8.3%, respectively. Z‐scores were lower with older age, female sex, body mass index (BMI) <5th percentile, boosted PI exposure and CD4 T‐cell percentage < 15% before ART initiation. Increased bone turnover markers were inversely associated with BMD and BMAD Z‐scores.Conclusions: Low bone mass was linked to older age, female sex, low BMI, boosted PI exposure, and poor immunological status before ART commencement in our cohort of perinatally HIV‐infected Asian adolescents. Dysregulation of bone turnover was associated with bone demineralization. Screening for low bone mass should be implemented to identify individuals who might benefit from interventions to preserve bone health.

Background. This phase 2/3, randomized, placebo-controlled, observer-blinded study assessed the immunogenicity, reactogenicity, and safety of an inactivated, split-virion H5N1 influenza vaccine (A/Indonesia/5/2005) in children aged 6 months through 17 years. Methods. Children received 2 influenza vaccine doses 21 days apart, each containing 1.9 µg of hemagglutinin and AS03_B adjuvant (5.93 mg of α-tocopherol). The randomization ratio was 8:3 for vaccine to placebo, with equal allocation between 3 age strata (6–35 months, 3–8 years, and 9–17 years). Immunogenicity against the vaccine strain was assessed 21 days after the first and second vaccine doses for all vaccinees, at day 182 for half, and at day 385 for the remaining half. Reactogenicity after each dose and safety up to 1 year after vaccination were evaluated. Results. Within each age stratum, the lower limit of the 98.3% confidence interval for the day 42 seroprotection rate was ≥70%, thus fulfilling the US and European licensure criteria. The immune responses elicited by vaccine persisted well above baseline levels for 1 year. The vaccine was more reactogenic than placebo, but no major safety concerns were identified. Conclusions. AS03_B-adjuvanted H5N1 influenza vaccine was immunogenic and showed an acceptable safety profile in all age groups studied. Clinical Trials Registration. NCT01310413.

Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children. This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9months to <5years in Thailand as a primary (Group 1) or booster (Group 2) vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30min after JE-CV administration were also described. The median age of participants was 1.1years in Group 1 and 3.8years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (<0.1%) in Group 2. There were no cases of Japanese encephalitis reported. No Grade 3 immediate systemic AEs were reported after any JE-CV vaccination. Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052).