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Abstract ChulaCov19 mRNA vaccine demonstrated promising phase 1 results. Healthy adults aged 18–59 years were double-blind randomised 4:1 to receive two intramuscular doses of ChulaCov19 50 µg or placebo. Primary endpoints were safety and microneutralization antibody against-wild-type (Micro-VNT50) at day 50. One hundred fifty adults with median (IQR) age 37 (30–46) years were randomised. ChulaCov19 was well tolerated, and most adverse events were mild to moderate and temporary. Geometric mean titres (GMT) of neutralizing titre against wild-type for ChulaCov19 on day 50 were 1367 IU/mL. T-cell IFN-γ-ELISpot showed the highest responses at one week (Day29) after dose 2 then gradually declined. ChulaCov19 50 µg is well tolerated and elicited high neutralizing antibodies and strong T-cell responses in healthy adults. Trial registration number: ClinicalTrials.gov Identifier NCT04566276, 28/09/2020.

Objective: To compare the immune response of hybrid immunity – arising from SARS-CoV-2 infection and mRNA BNT162b2 vaccination – to that of 2-doses of vaccine. Methods: In a subanalysis of BNT162b2 vaccine trial in 5 to 11-year-old children, There were 179 children who had hybrid immunity compared with 134 children with solely 2-dose vaccine. The immunological outcome was a surrogate virus neutralization test (sVNT) against the Omicron strain, BA.1, (%inhibition). An sVNT level ≥68 % inhibition was considered as protective immune response. Results: From February to April 2022, 179 children had COVID-19 natural infection resulting in hybrid immunity included: Group1;prior vaccination(n = 17), Group2;after the first dose(n = 61), and Group3;after the second dose(n = 97). The proportion of children with protective immune response was higher in Group 3 and Group 1 – 61.9 % and 58.8 %, compared to 36.1 % and 34.3 % in Group 2 and comparator group (2 doses of vaccine), respectively. The geometric mean % inhibition of sVNT was higher in Group 1 (68.5, 95 %CI 55.5–84.6) and Group 3 (63.5, 95 %CI 55.5–72.6), followed by comparator group (49.6, 95 %CI 44.8–54.9) and Group 2 (42.1, 95 %CI 34.6–51.3), p

Background: Children 6 months to 6 months(N = 40) prior to vaccination. Participants in Group A and B received 2-dose BNT162b2 intramuscularly 1 month apart. COVID-naïve children were enrolled as a control group (N = 40) and received 3-dose BNT162b2 at month 0,1,3. Neutralizing antibody against Omicron variant(BA.2.75 and BA.4/5) was determined by pseudovirus assays(pVNT) as reported by neutralization dilution for 50%inhibition (ID50) at 28 days after the 1st and 2nd dose. Results: From October-November 2022, 120 children with a median age of 2.8 years (IQR 1.6–4.0) were enrolled. The median duration since COVID-19 to vaccination was 4.4 months(IQR 3.8–5.4) in Group A and 7.9 months(7.0–8.5) in Group B. In Group A, the geometric means(GMs) of pVNT-BA.2.75 ID50 were 553 (95%CI 338–906) and 753(516–1098) after 1 and 2 doses, respectively, and the GMs of pVNT-BA.4/5 ID50 were 1936(1402–2673) and 1885(1414–2512), respectively. In Group B, the GMs of pVNT-BA.2.75 ID50 were 1383(1100–1742) and 1419 (1104–1823), and the GMs of pVNT-BA.4/5 ID50 were 2627(2048–3367) and 2056(1546–2735), respectively. Meanwhile in COVID-naïve group, the GMs of pVNT-BA.2.75 and pVNT-BA.4/5 ID50 were 158(98–255) and 59(31–114) after the 3rd dose, respectively. The geometric mean ratio(GMR) of pVNT-BA.2.75 ID50 after 1 dose in Group A and B compared with after 3 doses in COVID-naïve group were 3.50 (1.93–6.34) and 8.74 (4.79–15.95), respectively. The GMR of pVNT-BA.2.75 ID50 after 1 dose in Group B compared with Group A was 2.50 (1.45–4.31). Conclusions: Children previously infected with SARS-CoV-2 Omicron variant, developed robust neutralizing antibody response against Omicron variant after single-dose BNT162b2. Children with an interval of > 6 months since COVID-19 infection developed higher neutralizing antibody response compared to those with a 3-to-6-month interval.

Objectives: To evaluate the immunogenicity of an extended interval regimen of BNT162b2 among healthy school-age children. Methods: A randomized-control trial conducted among healthy Thai children aged 5-11 years. Participants received two doses of BNT162b2 with an 8-week (extended dosing) vs 3-week interval. Immunogenicity was determined by neutralization test (NT) against the Omicron variant, surrogate virus NT (sVNT; BA.1, % inhibition), and pseudovirus NT (BA.2, the half-maximal inhibition dilution or ID50). The third dose was offered to participants who had sVNT

Abstract Background Same-day antiretroviral therapy (SDART) initiation, in which people living with HIV (PLHIV) who are antiretroviral therapy (ART)-naïve, willing, and clinically eligible start ART on the same day of HIV diagnosis, has been implemented in several healthcare facilities in Thailand since 2017. This evidence-based practice has demonstrated increased ART uptake, virologic suppression, and retention in care. However, linkage to care gaps exist in community-based organizations (CBOs) in Bangkok whereby as much as 20% of key populations (KP), mainly men who have sex with men and transgender women, living with HIV were lost to follow-up pre-ART initiation. To increase access to and uptake of ART among these populations, this study proposes that trained KP lay providers should lead community-based ART (CB-SDART) initiation service. This protocol describes the combined use of the Proctor’s implementation outcome framework and the Consolidated Framework for Implementation Research to guide and evaluate the CB-SDART implementation. Methods This study follows the hybrid design type 3: it is an implementation trial that secondarily assesses service and client outcomes by comparative interrupted time series analysis. Five strategies have been formulated to meet three implementation outcomes (i.e., feasibility, fidelity, and sustainability): (1) developing stakeholder relationships by engaging the CBO leaderships, (2) training and educating KP lay providers, (3) adapting and tailoring SDART to CBO-specific context, (4) using evaluative and iterative strategies to assess adherence to standard operating procedures, and (5) developing stakeholder relationships by engaging external stakeholders. Teleconsultation with physicians and ART home delivery will be integrated as another ART initiation option for clients and allow service provision during the COVID-19 pandemic. A mixed-method assessment will be conducted on key stakeholders and PLHIV diagnosed at two implementing CBOs, Rainbow Sky Association of Thailand and Service Workers in Group Foundation, in Bangkok, Thailand. Discussion This implementation research may be the first to provide robust data at the implementation, service, and client levels to inform how to successfully task-shift SDART initiation service to trained KP lay providers and facilitate the expansion of CB-SDART in the future. Trial registration This trial was registered with the Thai Clinical Trial Registry as TCTR20210709004 on July 9, 2021.

Objectives: To evaluate the pharmacokinetic parameters of the 2020 World Health Organization (WHO)-recommended pediatric dosage of levofloxacin and the higher-than-WHO dosage. Methods: Children aged 1-15 years with tuberculosis who received levofloxacin-based treatment for at least 7 days were enrolled. First, five children were enrolled to receive the WHO-recommended dosage (15-20 mg/kg/day), then an additional five children received a dosage higher than the WHO-recommended dosage (20-30 mg/kg/day). Blood samples were collected at predose and postdose 1, 2, 4, 6, 8, and 12 hours. A target of the ratio of the free area under the concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was 100. Results: The median (interquartile range) age was 9.6 (4.9-10.5) and 12.0 (10.1-12.3) years in the WHO dosage and higher-than-WHO dosage groups, respectively. The median (interquartile range) duration of antituberculosis treatment was 24 (8-24) weeks. The geometric mean (95% confidence interval) of fAUC/MIC was 60.4 (43.5-84.0) and 103.2 (70.1-151.8) in the WHO and higher-than-WHO dosage groups, respectively. There was no adverse event of QT prolongation or any other grade 3 or 4 adverse events. Conclusion: Levofloxacin at a higher dose of 20-30 mg/kg/day could achieve the fAUC/MIC target in children.

Objectives: This study investigated the steady-state pharmacokinetic profiles of 3-month weekly rifapentine plus isoniazid (3HP) in children with latent tuberculosisinfection (LTBI). We also assessed other factors, including tablet integrity, food, and pharmacogenetics. Methods: During the 3HP treatment, blood and urine samples were collected in week 4. Isoniazid and rifapentine levels were measured using a high-performance liquid chromatography technique. The genetic variation of arylamine N-acetyltransferase 2 (NAT2) and arylacetamide deacetylase (AADAC) were assessed by the MassARRAY®. Safety and clinical outcomes at week 48 were monitored. Results: A total of 12 children with LTBI (age 3.8 [range 2.1-4.9 years old]) completed the treatment (isoniazid and rifapentine dose 25.0 [range 21.7-26.8] and 25.7 [range 20.7-32.1] mg/kg, respectively). No serious adverse events or active TB occurred. Tablet integrity was associated with decreased area under the concentration-time curve (91 vs 73 mg.h/l, P= 0.026) and increased apparent oral clearance of isoniazid (0.27 vs 0.32 l/h/kg, P= 0.019) and decreased rifapentine's renal clearance (CLR, 0.005 vs 0.003 l/h, P= 0.014). Food was associated with increased CLR of isoniazid (3.45 vs 8.95 l/h, P= 0.006) but not rifapentine. Variability in NAT2 and AADAC did not affect the pharmacokinetics of both drugs. Conclusion: There is high variability in the pharmacokinetic profiles of isoniazid and rifapentine in young children with LTBI. The variability was partly influenced by tablet integrity and food, but not pharmacogenetics. Further study in a larger cohort is warranted to display the relationship of these factors to treatment outcomes.

Introduction The Thai National AIDS programme (NAP) treatment guidelines have recommended rapid antiretroviral therapy (ART) initiation, regardless of CD4 count since 2014. We assessed treatment outcomes among youth living with HIV (YLHIV), initiating first‐line ART and assessed the association between virological failure (VF) and timing of ART initiation. Methods We retrospectively reviewed data for YLHIV aged 15–24 years, initiating non‐nucleoside reverse transcriptase inhibitor‐based ART from 2014 to 2019, through the NAP database. We classified the timing of ART into three groups based on duration from HIV‐positive diagnosis or system registration to ART initiation: (1) 3 months (delayed ART). VF was defined as viral load (VL) ≥ 1000 copies/ml after at least 6 months of first‐line ART. Factors associated with VF were analysed using generalized estimating equations. Results Of 19,825 YLHIV who started ART, 78% were male. Median (interquartile range, IQR) age was 21 (20–23) years and CD4 count was 338 (187–498) cells/mm3. After registration, 12,216 (62%) started rapid ART, 4272 (22%) intermediate ART and 3337 (17%) delayed ART. The proportion of YLHIV starting ART

Abstract 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 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

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

Background: Social network strategies (SNS) assumes that people in the same social share similar HIV risk. Methods: This study evaluated SNS to promote HIV testing of young men who have sex with men (YMSM) and transgender women (YTGW) aged 15–24 years. “Recruiters” referred their ‘network members’ (NMs) to clinic. NMs were provided HIV testing. Proportions of first-time HIV testers and number of NMs were analyzed. Results: Between April 2021 to March 2022, 83 recruiters referred 202 NMs. Median age of NMs was 19 years (IQR 17-20), 62% were YMSM. One-hundred-and-twenty-four NMs (61%) were first-time HIV testers. YTGW recruited more NMs per recruiter (5.4 vs 1.4, p = 0.002). HIV prevalence was 3.0% (95% CI 1.1-6.4). Thirty-one-point-three percent of NMs at HIV risk initiated oral HIV preexposure prophylaxis. Conclusions: SNS is a good strategy to reach adolescents at risk of HIV infection. More than half of NMs were first-time HIV testers.

Background: A primary series of 2-dose SARS-CoV-2 vaccines based on an ancestral strain generate inadequate neutralizing antibodies against the SARS-CoV-2 Omicron variant. This study aimed to describe the immune response from giving healthy school-aged children who previously received 2 inactivated vaccines an mRNA BNT162b2 booster. Methods: Healthy children aged 5–11 years who received 2 doses of CoronaVac or Covilo were enrolled and received 10 µg BNT162b2 intramuscularly. Neutralizing antibody against Omicron variant was measured at pre-booster and 14–21 days post-booster by surrogate virus neutralization test (sVNT, %inhibition) and pseudovirus neutralization test (pVNT, ID50). Antibody responses were compared with a parallel cohort of children who received 2 doses of BNT162b2 3 weeks apart. Results: From April to May 2022, 59 children with a mean age (SD) of 8.5 years (1.7) were enrolled: 20 CoronaVac and 39 Covilo recipients. The median interval from the primary series was 49 days (IQR 33–51). After booster, the geometric means (GMs) of sVNT and pVNT were 72.2 %inhibition (95 %CI 67.2–77.6) and 499 (95 %CI 399–624), respectively. The proportion of children with sVNT against Omicron strain ≥68 %inhibition increased from none to 70.2 %. The geometric mean ratio (GMR) of sVNT and pVNT compared with a parallel cohort were 4.3 and 12.2, respectively. The GMR of sVNT and pVNT between children who received booster dose at >6-week interval were 1.2 (95 %CI 1.1–1.3). and 1.8 (95 %CI 1.2–2.7) compared with 4–6 weeks interval. Conclusion: A regimen of 2-dose of inactivated vaccine followed by BNT162b2 booster dose elicited high neutralizing antibody against the Omicron variants in healthy school-aged children.

Background: Heterologous prime-boost SARS-CoV-2 vaccination is a widely accepted strategy during the COVID-19 pandemic, which generated a superior immune response than homologous vaccination strategy. Objective: To describe immunogenicity of heterologous prime-boost vaccination with inactivated vaccine, CoronaVac, followed by BNT162b2 and 5-month booster dose with BNT162b2 in healthy Thai adolescents. Methods: Adolescents aged 12–18 years were randomized 1:1:1:1 to receive CoronaVac (SV) followed by BNT162b2 (PZ) 30 or 20 µg at either 3- or 6-week interval (SV3w/PZ30µg, SV3w/PZ20µg, SV6w/PZ30µg or SV6w/PZ20µg). During the Omicron-predominant period, participants were offered a BNT162b2 booster dose 30, 15, or 10 µg. Immunogenicity was determined using IgG antibody against spike-receptor-binding domain of wild type(anti-S-RBD IgG) and surrogate virus neutralization test(sVNT) against Delta variant at 14 days and 5 months after the 2nd dose. Neutralization tests(sVNT and pseudovirus neutralization test; pVNT) against Omicron strain were tested pre- and 14 days post-booster dose. Results: In October 2021, 76 adolescents with a median age of 14.3 years (IQR 12.7–16.0) were enrolled: 20 in SV3w/PZ30µg; 17 in SV3w/PZ20µg; 20 in SV6w/PZ30µg; 19 in SV6w/PZ20µg. At day 14, the geometric mean(GM) of anti-S-RBD IgG in SV3w/PZ30µg was 4713 (95 %CI 4127–5382) binding-antibody unit (BAU)/ml, while geometric mean ratio(GMR) was 1.28 (1.09–1.51) in SV6w/PZ30µg. The GMs of sVNT against Delta variants at day 14 among participants in SV3w/PZ30µg and SV6wk/PZ30µg arm were 95.3 % and 99.7 %inhibition, respectively. At 5 months, GMs of sVNT against Delta variants in SV3w/PZ30µg were significantly declined to 47.8 % but remained at 89.0 % inhibition among SV6w/PZ30µg arm. In April 2022, 52 adolescents received a BNT162b2 booster dose. Proportion of participants with sVNT against Omicron strain > 80 %inhibition was significantly increased from 3.8 % pre-booster to 67 % post-booster. Proportion of participants with pVNT ID50 > 185 was 42 % at 14 days post 2nd dose and 88 % post booster, respectively. Conclusions: Heterologous prime-boost vaccination with CoronaVac followed by BNT162b2 induced high neutralizing titer against SARS-CoV-2 Delta strain. After 5-month interval, booster with BNT162b2 induced high neutralizing titer against Omicron strain.Thai Clinical Trials Registry (thaiclinicaltrials.org): TCTR20210923012.

Objectives: The World Health Organization recommends a 2-dose rabies pre-exposure prophylaxis (PrEP) regimen. This study aimed to compare the immunogenicity of rabies PrEP regimens co-administered with inactivated quadrivalent influenza vaccine (IIV4). Methods: Children aged 3 to 9 years were randomly assigned (2:2:1) to receive 0.25 mL of chromatographically purified Vero cell rabies vaccine intramuscularly: Group A at day 0, 7 with IIV4; Group B at day 0, 28 with IIV4; Group C at day 0, 7. A booster-dose of CPRV was given on day 365. Primary outcome was the proportion of children with protective rabies virus neutralizing antibody (RVNA) ≥ 0.5 IU/mL, on day 42 and 7 days post-booster. Results: From November 2019 to January 2020; 100 children with a median age (IQR) of 5.4 years (4.8-7.3) were enrolled. All participants achieved protective RVNA titers on day 42 and 7-days post booster. Geometric mean titers (GMT) at day 42 were Group A, 8.98(95%CI 7.06-11.42); Group B, 23.89(95%CI 19.33-29.51); Group C, 9.94(95%CI 7.03-14.06). Likewise, RVNA GMT at 7 days post-booster were Group A, 42.53(95%CI 18.41-66.64); Group B, 23.19(95%CI 17.28-29.10); Group C, 57.75 (95%CI 35.86-79.67). Conclusions: The 2-dose PrEP regimen of rabies vaccine produces adequate immune response either 0,7 or 0, 28 regimens.

Objectives: The aim of this study was to describe the population pharmacokinetics of intravenous colistin use in children and to propose optimal dosage regimens. Methods: A prospective, multicenter, population pharmacokinetic (PPK) study was conducted. Phoenix 64 version 8.3 was used for the PPK analysis. Simulations were performed to estimate the probability of target attainment for patients achieving target plasma colistin average steady-state concentrations (Css,avg). Results: A total of 334 plasma colistin concentrations were obtained from 79 pediatric patients with a median age (interquartile range) of 2.6 years (0.8−6.8 years); 73 (92.4%) were admitted to intensive care units. Colistin pharmacokinetics were adequately described by a one-compartment model with first-order elimination along with serum creatinine (SCr) as a significant covariate in colistin clearance. The simulation demonstrated that the recommended dose of 5 mg of colistin base activity (CBA)/kg/day resulted in 18.2−63.0% probability of achieving a target Css,avg of 2 mg/l. With a lower targeted Css,avg of 1 mg/l, colistin dosing with 7.5 mg and 5 mg of CBA/kg/day were adequate for children with SCr levels of 0.1−0.3 mg/dl and >0.3 mg/dl, respectively. Conclusions: SCr is a significant covariate in colistin clearance in children. Colistin dosing should be selected according to the patient's SCr level and the desired target Css,avg.

Objectives: To be effective, piperacillin/tazobactam (PTZ) unbound plasma levels need to be above the minimum inhibitory concentration (MIC) at least 50% of the time between dosing intervals (50% fT>MIC). This study aimed to compare the plasma piperacillin concentrations at the mid-dosing intervals (Cmid, 50% fT) and the proportion of patients achieving 50% fT>MIC between extended infusion (EI) and intermittent bolus (IB) methods in children. Methods: A prospective, randomised trial of EI versus IB of PTZ was conducted in children aged 1 month to 18 years. The PTZ dose was 100 mg/kg intravenously every 8 h. Patients were randomly assigned to receive EI (4-h infusion) or IB (30-min infusion). The primary outcome that was measured was plasma piperacillin Cmid. Results: Ninety patients with a median age (IQR) of 48 months (16–127) were enrolled. The most common indication for PTZ use was pneumonia (32.2%). Geometric mean (95% CI) plasma piperacillin Cmid of EI versus IB was 51.9 mg/L (40.6–66.6) versus 6.0 mg/L (4.2–8.6) (P < 0.01). The EI group had a trend of higher proportion of patients who achieved 50% fT>4xMIC (72.7% versus 30.0%; P = 0.06). Conclusions: PTZ administration with EI resulted in a higher Cmid compared with IB. In settings with increased piperacillin MICs, this approach should be implemented, particularly during the empirical treatment period.

Objectives: A colistin loading dose is required to achieve adequate drug exposure for the treatment of multidrug-resistant Gram-negative bacteria. However, data on acute kidney injury (AKI) rates associated with this approach in children have been unavailable. The aim of this study was to examine AKI rates in children who were prescribed a colistin loading dose. Methods: A retrospective study was conducted in patients aged 1 month to 18 years who had received intravenous colistin for ≥48 h. Loading dose (LD) was defined as colistin methanesulfonate at 4–5 mg of colistin base activity/kg/dose. AKI was defined according to KDIGO serum creatinine (SCr) criteria — SCr ≥ 1.5 times the baseline, measured 3–7 days after colistin initiation. Augmented renal clearance (ARC) was defined as an estimated glomerular filtration rate (eGFR) >150 mL/min/1.73 m2. The rates of AKI were compared between children receiving or not receiving an LD, and between different eGFR groups. Results: In total, 181 children were enrolled. The mean age was 4.3 years (95% confidence interval [CI], 3.6–4.9 years). Ninety-five of the subjects (52.5%) were male. There were 157 children with a baseline eGFR of ≥ 80 mL/min/1.73 m2. The overall AKI rate within the first week in this group was 20.4% (95% CI, 14.4–27.6%): LD, 16.1% vs no LD, 23.2% (p = 0.29). Subgroup analysis, excluding patients with ARC, showed a lower AKI rate of 12.8% (95% CI, 6.8–21.3%): LD, 9.7% vs no LD, 14.3% (p = 0.53). Conclusions: AKI rate was not different among children who received an intravenous colistin loading dose. This approach should be implemented to ensure the necessary drug exposure required for good treatment outcomes.

This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5–11) and adolescents (aged 12–17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron variant. We enrolled 97 children and 57 adolescents. At 3 months, 30 children (31%) and 34 adolescents (60%) reported at least one long COVID symptom, with respiratory symptoms prevailing (25% children and 32% adolescents). The median time from infection to vaccination was 3 months in adolescents and 7 months in children. At 1 month following vaccination, in children who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 86.2% inhibition (71.1–91.8) and 79.2% inhibition (61.5–88.9), respectively (p = 0.26). Among adolescents who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 64.4% inhibition (46.8–88.8) and 68.8% inhibition (65.0–91.2) (p = 0.64). Adolescents had a higher prevalence of long COVID than children. Immunogenicity against the Omicron variant after vaccination was high and did not vary between one or two doses of the vaccine in either children or adolescents.

To treat critically ill patients, early achievement of the target area under the plasma concentration-time curve/minimum inhibitory concentration (AUC/MIC) in the first 24 h is recommended. However, accurately calculating the AUC before steady state is an obstacle to this goal. A first-order pharmacokinetic equation to calculate vancomycin AUC after a first dose of vancomycin has never been studied. We sought to estimate AUC using two first-order pharmacokinetic equations, with different paired concentration time points, and to compare these to the actual first dose vancomycin AUC calculated by the linear-log trapezoid rule as a reference. The equations were validated using two independent intensive first dose vancomycin concentration time data sets, one from 10 adults and another from 14 children with severe infection. The equation with compensation for the alpha distribution phase using a first vancomycin serum concentration from 60 to 90 min and the second concentration from 240 to 300 min after the completed infusion showed good agreement and low bias of calculated AUC, with mean differences 0.96. Moreover, it gave an excellent correlation with Pearson’s r > 0.96. Estimating the first dose vancomycin AUC calculated using this first-order pharmacokinetic equation is both reliable and reproducible in clinical practice settings.

Objective: Antibiotics are frequently prescribed for the treatment of acute lower respiratory infections (ALRI) in children ≤5 years of age, even though viral aetiologies are the most common. The aim of this study was to describe antibiotic prescribing rates and patterns in children ≤5 years of age hospitalized with ALRI. Methods: A retrospective study was conducted involving patients aged 1 month to 5 years hospitalized with ALRI at a university hospital. Patient demographics, ALRI diagnosis, microbiological data, antibiotics prescribed, and treatment outcomes were recorded and analysed. Results: A total of 1283 patients were enrolled. Their median age was 1.6 years (interquartile range 0.8–2.8 years). Thirty-six percent had a co-morbidity. The diagnosis at discharge was viral ALRI in 81% and bacterial pneumonia in 19%. The mortality rate was 0.4%. The overall antibiotic prescribing rate was 46% (95% confidence interval 43–49%). Antibiotic prescribing rates were higher among children with co-morbidities (65% vs 35%, p < 0.001) and older children (57% for >2–5 years vs 39% for ≤2 years, p < 0.001). Parenteral third-generation cephalosporins were prescribed in up to 68% of all prescriptions. Conclusions: Nearly-half of hospitalized children with ALRI were prescribed antibiotics. The majority of prescribed antibiotics were third-generation cephalosporins. An antimicrobial stewardship programme and antibiotic guidelines should be implemented to promote the judicious use of antibiotics.

Abstract Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children

BackgroundWidespread smartphone use provides opportunities for mobile health HIV prevention strategies among at-risk populations. ObjectiveThis study aims to investigate engagement in a theory-based (information–motivation–behavioral skills model) mobile phone app developed to support HIV pre-exposure prophylaxis (PrEP) adherence among Thai young men who have sex with men (YMSM) and young transgender women (YTGW) in Bangkok, Thailand. MethodsA randomized controlled trial was conducted among HIV-negative YMSM and YTGW aged 15-19 years initiating daily oral PrEP. Participants were randomized to receive either youth-friendly PrEP services (YFS) for 6 months, including monthly contact with site staff (clinic visits or telephone follow-up) and staff consultation access, or YFS plus use of a PrEP adherence support app (YFS+APP). The target population focus group discussion findings and the information–motivation–behavioral skills model informed app development. App features were based on the 3Rs—risk assessment of self-HIV acquisition risk, reminders to take PrEP, and rewards as redeemable points. Dried blood spots quantifying of tenofovir diphosphate were collected at months 3 and 6 to assess PrEP adherence. Tenofovir diphosphate ≥350-699 fmol/punch was classified as fair adherence and ≥700 fmol/punch as good adherence. Data analysis on app use paradata and exit interviews were conducted on the YFS+APP arm after 6 months of follow-up. ResultsBetween March 2018 and June 2019, 200 participants with a median age of 18 (IQR 17-19) years were enrolled. Overall, 74% (148/200) were YMSM; 87% (87/100) of participants who received YFS+APP logged in to the app and performed weekly HIV acquisition risk assessments (log-in and risk assessment [LRA]). The median duration between the first and last log-in was 3.5 (IQR 1.6-5.6) months, with a median frequency of 6 LRAs (IQR 2-10). Moreover, 22% (22/100) of the participants in the YFS+APP arm were frequent users (LRA≥10) during the 6-month follow-up period. YMSM were 9.3 (95% CI 1.2-74.3) times more likely to be frequent app users than YTGW (P=.04). Frequent app users had higher proportions (12%-16%) of PrEP adherence at both months 3 and 6 compared with infrequent users (LRA

BackgroundDespite a successful antiretroviral therapy (ART), adolescents living with perinatally acquired HIV (PHIV) experience signs of B-cell hyperactivation with expansion of ‘namely’ atypical B-cell phenotypes, including double negative (CD27-IgD-) and termed age associated (ABCs) B-cells (T-bet+CD11c+), which may result in reduced cell functionality, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. In this context, perinatally HIV infected children (PHIV) deserve particular attention, given their life-long exposure to chronic immune activation.MethodsWe studied 40 PHIV who started treatment by the 2nd year of life and maintained virological suppression for 13.5 years, with 5/40 patients experiencing transient elevation of the HIV-1 load in the plasma (Spike). We applied a multi-disciplinary approach including immunological B and T cell phenotype, plasma proteomics analysis, and serum level of anti-measles antibodies as functional correlates of vaccine-induced immunity.ResultsPhenotypic signs of B cell hyperactivation were elevated in subjects starting ART later (%DN T-bet+CD11c+ p=0.03; %AM T-bet+CD11c+ p=0.02) and were associated with detectable cell-associated HIV-1 RNA (%AM T-bet+CD11c+ p=0.0003) and transient elevation of the plasma viral load (spike). Furthermore, B-cell hyperactivation appeared to be present in individuals with higher frequency of exhausted T-cells, in particular: %CD4 TIGIT+ were associated with %DN (p=0.008), %DN T-bet+CD11c+ (p=0.0002) and %AM T-bet+CD11c+ (p=0.002) and %CD4 PD-1 were associated with %DN (p=0.048), %DN T-bet+CD11c+ (p=0.039) and %AM T-bet+CD11c+ (p=0.006). The proteomic analysis revealed that subjects with expansion of these atypical B-cells and exhausted T-cells had enrichment of proteins involved in immune inflammation and complement activation pathways. Furthermore, we observed that higher levels of ABCs were associated a reduced capacity to maintain vaccine-induced antibody immunity against measles (%B-cells CD19+CD10- T-bet+, p=0.035).ConclusionWe identified that the levels of hyperactivated B cell subsets were strongly affected by time of ART start and associated with clinical, viral, cellular and plasma soluble markers. Furthermore, the expansion of ABCs also had a direct impact on the capacity to develop antibodies response following routine vaccination.

Background Pneumococcal diseases among children aged 0.35 μg/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P97% of the subjects in each group achieved IgG concentrations of ≥0.35 μg/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003). Conclusion The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.

Abstract Background Screening for sexually transmitted infection (STI) especially HIV as early detection and treatment have been financially supported under the Thai Universal Coverage (UC) scheme since 2009 (THB140 for HIV). However, the implementation has not been evidence-based, strategic risk-based, nor economically evaluated whereas husbands who accompanied the pregnant women are likely to have a lower risk than those who did not come along. This study is aimed to determine the husband’s willingness-to-pay (WTP) for his HIV and syphilis screening tests and potential factors affecting STI screenings at the antenatal care (ANC) clinic of a tertiary hospital in Thailand. Methods A pilot open-ended interview was conducted among 50 participants to estimate the mean and standard deviation of WTP prices for HIV and syphilis screening tests. A questionnaire was developed to obtain demographics, STI knowledge and screening history, as well as two contingent valuation methods (bidding and payment scale), using the mean WTP prices identified from the pilot study as a starting WTP with ¼SD step-up/down. The survey of 200 randomly selected husbands of pregnant women was conducted at King Chulalongkorn Memorial Hospital from April to June 2018. Descriptive statistics and logistic regression were used for data analysis. Results During the study period, 597 pregnant women received their first ANC. Of 368 accompanying husbands, 200 were enrolled in the study. Their median age was 31 (IQR 27–36) years old and 67% had a first child. Eighty-eight percent of the participants were willing to test for the STIs. Based on the bidding method, WTP prices for HIV and syphilis screening tests were US$14.5 (IQR 12.4–14.5) and US$9.7 (IQR 10–12), respectively. The payment scale method suggested approximately three-quarters of the WTP prices from the bidding method. Conclusions The husbands who accompanied their pregnant wives to the ANC clinic showed positive behaviors according to the propitious selection theory. They tend to cooperate well with STI testing and are willing to pay at least two times the price of the STI screening tests. The financial support to promote STI screenings should be reconsidered to cover other groups with higher sexual behavior risks and less WTP.

BackgroundHIV disproportionately affects young Thai men who have sex with men (YMSM). Recent studies report a high incidence and prevalence of HIV among Thai YMSM. The Thai national guidelines have recommended pre-exposure prophylaxis (PrEP) since 2014 for key populations; free PrEP has been piloted since 2019. Smartphone-based mobile health (mHealth) interventions provide an optimal platform for innovative PrEP adherence interventions for Thai YMSM. ObjectiveThis study aims to adapt the P3 (Prepared, Protected, emPowered) app, developed with YMSM and transwomen in the United States to improve PrEP adherence and persistence for YMSM in Thailand. The app aims to provide daily adherence support and addresses gaps in staff available for large-scale PrEP rollout needed to see population-level effects of HIV prevention. MethodsWe conducted focus group discussions (FGDs) with YMSM and key informant interviews (KIIs) with PrEP care providers in Bangkok, Thailand, to investigate PrEP adherence facilitators and barriers, preferences for functions and features in mHealth apps among YMSM, and how to best adapt the P3 app to the Thai context. We conducted four FGDs with 4-8 participants per group and 15 KIIs. ResultsFor FGDs, 23 YMSM participated with a mean age of 20 years (range 18-21), 96% (22/23) enrolled in full-time education, and all owned smartphones. The mean age of KII participants was 40 (range 26-60) years; most were state health service providers, with the majority being counselors (6/15, 40%) and physicians (6/15, 40%). Overall, the facilitators and barriers for PrEP adherence identified were similar to those of MSM and YMSM globally including the United States. Key themes included general recommendations for improving mHealth apps in Thailand, such as presenting reliable information in an appealing format, minimizing privacy risks, and addressing connectivity challenges. Additional themes focused on P3 Thailand adaptations and were related to cultural and stylistic preferences, engagement strategies, and recommendations for new functions. To develop the adapted app, P3 Thailand, these findings were balanced with resource limitations resulting in the prioritization of minor modifications: changes in app esthetics (color scheme, iconography, and imagery) and changes in the presentation of information in two of the app’s features. FGDs identified similar PrEP adherence facilitators and barriers to those already addressed within the app. ConclusionsThe core elements of the P3 app address major PrEP facilitators and barriers for Thai YMSM; however, changes to the app features, including stylistic presentation, were needed to appropriately customize the app to the Thai context. Given the similarities of facilitators and barriers for PrEP adherence globally, adapting existing PrEP mHealth solutions based on input from end users and key informants provides a promising approach. However, partnerships with local app designers and developers can improve the adaptation process and final product. Trial RegistrationClinicalTrials.gov NCT04413708; http://clinicaltrials.gov/ct2/show/NCT04413708

Primary series vaccination with BNT162b2 followed by a booster 5 months later has been recommended for healthy adolescents. We aimed to describe the immunogenicity in a fractional dose of BNT162b2. Adolescents aged 12–18 years were randomized into six arms for primary series administration: 3wPZ30/30 (reference group), 3wPZ30/20, 3wPZ20/20, 6wPZ30/30, 6wPZ30/20, and 6wPZ20/20 μg. A booster was given at 5 months after the second dose using either 10 or 15 μg of BNT162b2. Immunogenicity following vaccination was determined by IgG against receptor-binding domain (anti-S-RBD IgG; BAU/mL), surrogate virus neutralization test (sVNT; %inhibition) and pseudovirus neutralization (pVNT;ID50) against Omicron. Non-inferiority criteria were defined as a lower boundary of the geometric mean ratio (GMR) being greater than 0.67. From September to October 2021, 118 adolescents with a median age (IQR) of 14.9 years (13.9–16.7) were enrolled. Fourteen days after the primary series, the geometric means (GMs) of anti-S-RBD IgG (BAU/mL) were 3090 (95% CI 2761–3460) in 3wPZ30/30. The GMRs of anti-S-RBD were: 0.80 (95% CI 0.67–0.97) in 3wPZ30/20; 1.00 (95% CI 0.83–1.20) in 3wPZ20/20; 1.37 (95% CI 1.13–1.65) in 6wPZ30/30; 1.24 (95% CI 1.02–1.50) in 6wPZ30/20; and 1.36 (1.13–1.64) in 6wPZ20/20. After a booster dose with 15 μg (n = 24) of BNT162b2, sVNT and pVNT against Omicron variant were 91.6 (95% CI 88.4–94.9) and 331 (95% CI 221–495), respectively. In the group that received 10 μg of BNT162b2 (n = 25), sVNT was 85.6 (95% CI 80.0–91.6) and pVNT was 397 (95% CI 267–590). Healthy adolescents had good immune responses to the fractional dose regimen of BNT162b2 and this may be considered as an alternative option.

Background: Children aged 6 months to 4 years have been recommended to receive three doses of BNT162b2, after COVID-19 infection, to immunize against SARS-CoV-2. Therefore, they might need fewer doses of vaccine compared with COVID-naïve children. Objective: To describe the immunogenicity of 2-dose BNT162b2 following COVID-19 in healthy young children previously infected with SARS-CoV-2. Materials and Methods: A prospective cohort study was conducted among children aged 6 months to 4 years who had SARS-CoV-2 infection during Delta-variant, which was July to November 2021, or Omicron-variant-predominant eras, which was February to August 2022. Participants received two doses of intramuscular BNT162b2 at an 8-week interval. Neutralizing antibodies against SARS-CoV-2 Omicron variant BA.4/5 were measured using pseudovirus neutralization tests (pVNT; ID50) at baseline and 28 days after the second dose. Results were compared with a parallel cohort of COVID-naïve children who received 3-doses of BNT162b2 at 0, 4 and 12 weeks. Results: Between November and December 2022, 80 children with a median age of 2.9 years (IQR 2.1 to 3.8) were enrolled. The median time from COVID-19 infection to the first dose was 13.8 months (IQR 13.8 to 16.2) in the Post-Delta Group, and 8.0 months (IQR 3.7 to 8.2) in the Post-Omicron Group. After 2-doses of BNT162b2, the geometric means (GMs) of pVNT increased from 105 (95% CI 48 to 231) to 863 (95% CI 638 to 1,168) in the Post-Delta Group and from 264 (95% CI 192 to 361) to 2,268 (95% CI 1,831 to 2,811) in the Post-Omicron Group. In comparison, the GM of pVNT was 59 (95% CI 31 to 114) in the parallel cohort of COVID-naïve children who received 3-doses of BNT162b2. Conclusion: Two doses of BNT162b2 were able to boost the immune response with high neutralizing antibodies against the circulating Omicron variant in children who were previously infected with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: There are limited data describing the care outcome of youth living with HIV in Asia. We assessed attrition and treatment outcomes among youths with behaviourly acquired HIV (BIY) and adolescents with perinatally acquired HIV (PIY) who initiated antiretroviral treatment (ART) through the National AIDS Program (NAP) in Thailand. Methods: People living with HIV aged 10–24 years who initiated antiretroviral therapy (ART) from 2008 to 2013 through the Thai NAP and who were followed up until 2014 were included in the analysis. We assessed youths initiating ART: BIY aged 15–19 years (BIY1) and BIY aged 20–24 (BIY2) compared against PIY aged 10–14 years. Attrition rates (mortality and loss to follow-up [LTFU]) were calculated and potential associations were assessed using Cox regression. Logistic regression was used to assess associations with treatment failure. Results: Of 11,954 individuals, 9909 (83%) were BIY with a median follow-up of 2.1 years and 17% were PIY with 4.2 years of follow-up. The median baseline CD4 cell count in BIY was higher (190 vs 154 cells/mm3) compared to PIY. Mortality rates were not significantly different among PIY (2.5 per 100 person years [PY], BIY1 3.1/100 PY and BIY2 2.9/100 PY, P=0.46). Compared to PIY with a crude LTFU rate of 2.9/100 PY, LTFU was higher in BIY1 (13.9/100 PY) and BIY2 (9.5/100 PY), P

To achieve the goal of measles elimination, herd immunity with 95% seroprotection in the community is required. This study aimed to describe the measles seropositivity rate among Thai children and adolescents. A cross-sectional study was conducted among children aged 3–18 years in Bangkok and its suburbs. Measles IgG antibodies were measured using a EUROIMMUN enzyme-linked immunosorbent assay kit. Seropositivity is defined as a measles IgG titer of ≥200 IU/L, due to a correlation with a >85% positive rate with a plaque reduction neutralizing titer of >120. Factors associated with seropositivity were analyzed using logistic regression analysis. From May to July 2020, 570 children with a median (IQR) age of 11.7 (9.4–14.8) years were enrolled. The geometric mean titer (GMT) of anti-measles IgG was 281 IU/L (95% CI; 257–306). The proportion of children with seropositivity was inversely correlated with age; 3–5 years 85.3%, 6–9 years 72.5%, 10–14 years 50.7%, and 15–18 years 56.3%. Adolescents aged 10–18 years had a lower measles seropositivity rate compared with young children; aOR 0.29 (95% CI 0.17–0.48). Only half of the adolescents who received two doses of measles-containing vaccine maintained measles IgG above the seropositive level. A measles booster dose for young adults may be needed to achieve the measles elimination goal.

Despite the BNT162b2 vaccination coverage, rapid transmission of Omicron SARS-CoV-2 has occurred, which is suspected to be due to the immune escape of the variant or waning vaccine efficacy of multiple BNT162b2 vaccination doses. Our study aims to compare immunogenicity against Omicron prior to and post a booster dose of BNT162b2 in healthy adolescents, and to evaluate their attitudes toward booster dose vaccination. A cross sectional study was conducted among healthy adolescents aged 12–17 who received two doses of BNT162b2 more than 5 months ago. Participants and their guardians performed self-reported questionnaires regarding reasons for receiving the booster. A 30 ug booster dose of BNT162b2 was offered. Immunogenicity was evaluated by a surrogate virus neutralization test (sVNT) against the Omicron variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) taken pre-booster and 14-days post-booster. From March to April 2022, 120 healthy Thai adolescents with a median age of 15 years (IQR 14–16) were enrolled. sVNT against Omicron pre- and post-booster had 11.9 (95%CI 0–23.9) and 94.3 (90.6–97.4) % inhibition. Geometric means (GMs) of anti-S-RBD IgG increased from 837 (728, 953) to 3041 (2893, 3229) BAU/mL. Major reasons to receive the booster vaccination were perceived as vaccine efficacy, reduced risk of spreading infection to family, and safe resumption of social activities. A booster dose of BNT162b2 elicits high immunogenicity against the Omicron variant. Motivation for receiving booster doses is to reduce risk of infection.

In the era of globally predominant omicron strains, a COVID-19 booster vaccine is needed. Our study aimed to evaluate the immunogenicity of a half-dose BNT162b2 booster after AZD1222 in healthy adults. A randomized trial of volunteers aged 18–69 years who received two-dose AZD1222 was conducted. The participants were randomized to receive the BNT162b2 vaccine intramuscularly—half (15 µg) vs. standard dose (30 µg). The immunogenicity was evaluated by a surrogate virus neutralization test (sVNT) against omicron variants and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG). From November–December 2021, 100 adults with a median age of 59.3 years (IQR 33.4–65.5) were enrolled. A booster dose was given at median of 98 days (IQR 92–128) after AZD1222. At day 14, the geometric means (GMs) of anti-S-RBD IgG in half- vs. standard-dose group were 2329.8 vs. 2574.7 BAU/mL, with a geometric mean ratio (GMR) of 0.90 (0.77–1.06). The GMs of sVNT against the omicron variant in the half- and standard-dose groups were 74.4% inhibition (95% CI 68.8–80.5) and 67.3% inhibition (57.9–78.1), respectively, with GMR of 0.95 (0.69–1.30). At day 90, the sVNT indicated 22.3% inhibition (95% CI 14.9–33.4) and 20.4% inhibition (13.1–32.0), respectively, with GMR of 1.09 (0.60–1.98). The fractional low-dose BNT162b2 mRNA booster vaccine provided non-inferior immunogenicity responses. During a shortage of vaccine supply, a fractional low dose should be considered for a booster vaccination program.

Abstract Background Cognitive and behavioral impairment are common in children living with perinatally acquired HIV (pHIV) and children exposed to HIV in utero but uninfected (HEU). Methods We sought to determine the prevalence of adverse behavioral symptomatology using a Thai-translated and validated version of the SNAP-IV questionnaire and assess cognitive function utilizing the Children's Color Trails Test, Delis-Kaplan Executive Function System, and the Wechsler Intelligence Scales, in our cohort of Thai adolescents (10–20 years old) with well-controlled pHIV compared to HEU and HIV-unexposed, uninfected youth. We then evaluated the interaction between HIV status, behavioral impairment, and executive function outcomes independent of demographic variables. Results After controlling for demographic factors of age and household income, adolescents with pHIV had higher inattentive symptomatology and poorer neuropsychological test scores compared to uninfected controls. Significant interactions were found between inattention and executive function across multiple neurocognitive tests. Conclusions Behavioral impairment and poor executive functioning are present in adolescents with well-controlled pHIV compared to HIV-uninfected matched peers. The SNAP-IV questionnaire may be a useful tool to identify those with attentional impairment who may benefit from further cognitive testing in resource-limited settings.

Adolescents with underlying diseases are at risk of severe COVID-19. The immune response of BNT162b2 may be poor among immunocompromised adolescents. We aim to describe immunogenicity of mRNA BNT162b2 among adolescents who are immunocompromised or have chronic diseases. We recruited adolescents 12–18 years of age; group A impaired-immunity (post-transplantation, cancer, on immunosuppressive drugs) and group B chronic diseases. A two-dose regimen of BNT162b2 was given. Immunogenicity was determined by surrogate virus neutralization test (sVNT) and IgG against receptor-binding domain (RBD). From August to October 2021, 312 adolescents, with a median age (IQR) of 15 years (13.7–16.5), were enrolled (group A 100, group B 212). The geometric means (GMs) of sVNT (% inhibition) against Delta strain and anti-RBD IgG (BAU/mL) after the 2nd dose among group A were: post-transplantation recipients 52.9 (95% CI 37.7–74.2) and 233.6 (95% CI 79–690.6); adolescents with cancer 62.3 (95% CI 29.2–133.1) and 214.9(95% CI 34.2–1348.6); and adolescents with other immunosuppressive conditions 66.7 (95% CI 52.4–84.8) and 849.8 (95% CI 393.4–1835.8). In group B were: adolescents living with HIV 98 (95% CI 97.3–98.8) and 3240.3 (95% CI 2699–3890.2), and adolescents with other chronic disease 98.6 (95% CI 98.3–98.9) and 3818.5 (95% CI 3490.4–4177.4). At day 90, immunity declined; among impaired-immunity participants were 43.9 (95% CI 30.8–62.4) and 178.7 (95% CI 91.2–350.1) and adolescents with chronic diseases were 90.6 (95% CI 88.4–92.8) and 1037.1 (95% CI 933.3–1152.5). In conclusion, adolescents with impaired immunity had a poor response to 2-doses of BNT162b2, additional dose should be considered. Adolescents with chronic diseases had excellent response but immunity waned after 3 m, booster dose may be required.

Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declines within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants who received ChAdOx1 and forty-two participants who received BNT162b2 were enrolled into this study, which evaluated immune responses, including anti-SARS-CoV-2 spike total antibodies (Elecsys®), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript), five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization, as well as 4 and 12 weeks after receiving the booster. This study showed a significant increase in anti-SARS-CoV-2 spike total antibodies, sVNT, and T-cell immune response after the booster, including against the Omicron variant. Immune responses rapidly decreased in the booster group at 12 weeks after booster but were still higher than post-primary vaccination. A fourth dose or a second booster should be recommended, particularly in health care workers.

BackgroundA greater understanding of the antibody response to SARS-CoV-2 in an infected population is important for the development of a vaccination.AimTo investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19.MethodsPlasma from the following patient groups was examined: 118 adult patients with confirmed SARS-CoV-2 infections, 49 patients under investigation (without confirmed infections), 20 patients with other respiratory infections, and 102 healthy control patients. Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from EUROIMMUN was performed to assess for IgA and IgG antibodies. The optical density (OD) ratio cutoff for a positive result was 1.1 for IgA and 0.8 for IgG. Additionally, the association of the antibody response with both the severity of disease and the date after onset of symptoms was analyzed.ResultsA total of 289 participants were enrolled and 384 samples analyzed from March 10 to May 31, 2020. Patients were categorized, based on their clinical manifestations, as mild (n = 59), moderate (n = 27), or severe (n = 32). The overall sensitivity of IgA and IgG from the samples collected after day 7 of the symptoms was 87.9% (95% CI: 79.8-93.6) and 84.8% (95% CI: 76.2-91.3), respectively. Compared to the mild group, the severe group had significantly higher levels of spike 1 (S1) antigen-specific IgA and IgG. All patients in the moderate and severe groups had S1-specific IgG, while 20% of the patients in the mild group did not have any IgG detected after two weeks after the onset of symptoms. Interestingly, in the severe group, the SARS-CoV-2 IgG level was significantly higher in males than females (p = 0.003).ConclusionThe serological test for SARS-CoV-2 has a high sensitivity more than two weeks after the onset of illness. Additionally, the serological response differs among patients based on sex as well as the severity of infection.

Objectives:The rate of vertical HIV transmission for women at high risk of HIV transmission stands at approximately 7.6%. In the present study we describe infant infection rates in women who had received raltegravir (RAL) intensification during pregnancy to a standard three-drug antiretroviral (ART) regimen in Thailand.Methods:This prospective cohort study enrolled HIV-1-positive pregnant women at high risk of vertical transmission, as defined by (1) ART initiation at a gestational age (GA) ≥32 weeks or (2) HIV-1 RNA >1000 copies/mL at GA of 32–38 weeks while on ART. Women received a standard three-drug ART regimen with RAL intensification (400 mg twice daily) until delivery and continued on a three-drug ART regimen after delivery. Plasma HIV-1 RNA testing was performed before intensification and at delivery. Infant HIV-1 status was determined using DNA PCR at birth, and at 1, 2 and 4 months of life.Results:Between February 2016 and November 2017, 154 pregnant women on ART were enrolled into the study with a median CD4 cell count and plasma HIV-1 RNA level of 382 cells/mm3 and 4.0 log10copies/mL, respectively. The three-drug combination consisted of either a lopinavir/ritonavir- (53%) or efavirenz-based (43%) regimen. Median GA at time of RAL initiation was 34 weeks (interquartile range [IQR] 33–36) and median duration was 21 days (IQR 8–34). The proportion of women who had a plasma HIV-1 RNA >50 and >1000 copies/mL at delivery was 45% and 76%, respectively. There were six infants with HIV infection, three in utero and three peripartum. Overall vertical transmission rate was 3.9% (95% confidence interval [CI] 1.4–8.2).Conclusion:The majority of high-risk pregnant women living with HIV-1 who had received RAL intensification achieved viral suppression at delivery with a relatively low rate of vertical transmission. This intensification strategy represents an option for prevention in HIV-positive women at high risk of vertical transmission.

Background: The benefits of calcium and vitamin D supplementation for low bone mass remains controversial. This study assessed the changes in bone mineral density (BMD) during periods without and with calcium and vitamin D supplementation among HIV-infected adolescents with low BMD.Method: Perinatally HIV-infected Thai adolescents aged 12–20 years were enrolled into Phase 1 (pre-supplementation) to evaluate longitudinal change of BMD. We provided education about appropriate dietary intake and exercise. Lumbar spine (L2–L4) BMD and vitamin D status (25-hydroxyvitamin D [25(OH)D]) were assessed at baseline and at 12–24 month intervals. Participants with a BMD Z-score≤−2 were enrolled into Phase 2 (supplementation) that provided calcium 600 mg plus cholecalciferol 200 IU twice daily for 6 months. BMD and 25(OH)D were re-assessed at the end of study.Results: Ninety-four participants were enrolled into the Phase 1. Median age (IQR) was 14.3 (13.0–15.5) years, with 67% at Tanner stage 3–5, 89% with a plasma HIV-1 RNA>50 copies/mL. During Phase 1 and a 22.7-month follow-up, median L2–L4 BMD Z-scores remained unchanged (−1.06 vs −1.08, P=0.08), but 25(OH)D levels increased (24.7 vs 26.7 ng/mL, P=0.01). Twenty-six (28%) adolescents had low BMD and were enrolled into Phase 2, with 24 (92%) completing follow-up. The median L2–L4 BMD Z-scores (−2.59 vs −1.70; P>0.001) and calcium level (9.3 vs 9.5 mg/dL, P=0.04) significantly improved. There was an increase in BMD Z-scores during the 6-months post-supplementation as compared to the 21-month pre-supplementation period (0.65 vs −0.50, P=0.03).Conclusion: HIV-infected adolescents with low BMD had improved bone health after calcium and vitamin D supplementation. A randomised controlled trial is warranted to confirm the benefits of these supplements.

Objective: To describe influenza and pertussis vaccine uptake among pregnant women before and after receiving an educational session. Materials and Methods: An interventional study was conducted at a tertiary care hospital and a specialized obstetric hospital in Thailand. In the first phase, the medical records of the non-intervention pregnant women received antenatal care (ANC) at the study sites were reviewed. In the second phase, the pregnant women completed a questionnaire about their knowledge and factors for vaccine acceptance then enrolled into the intervention, received an educational session. The vaccine uptake between phases were compared using chi-square test. Potential factors of vaccine acceptance were examined using multivariate logistic regression. Results: Between May 2019 and July 2020, 785 pregnant women were enrolled with 375 in the non-intervention group and 410 in the intervention group. The median age of the pregnant women was 30 years (IQR of 26 to 34). Influenza vaccine uptake among the non-intervention group was 55.5% compared to 65.6% in the intervention group (p=0.004). The factor for influenza vaccine acceptance was the total number of visits at the ANC clinic at ten times or more (OR 1.38, 95% CI 1.04 to 1.84, p=0.03). Pertussis vaccine uptake was 52.8% in the non-intervention group compared to 67.0% in the intervention group (p=0.001). The factor for pertussis vaccine acceptance was receiving ANC at the tertiary care hospital (aOR 6.73, 95% CI 4.42 to 10.27). The most common reasons for not getting the vaccine were the concern of vaccine safety with 25.6% for influenza vaccine and 26.3% for pertussis vaccine. Conclusion: The educational session increased the vaccine uptake for influenza and pertussis in Thai pregnant women. [ABSTRACT FROM AUTHOR]

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 RNA3.16). 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.

Background: Hepatitis B virus (HBV) and HIV coinfection is associated with risk of progression to chronic liver disease. We assessed liver stiffness in HBV-HIV coinfected youths. Methods: A cross-sectional study in HBV-HIV coinfected youths aged 18 to 25 years who received a tenofovir (TDF)-containing antiretroviral therapy regimen for >96 weeks. Measurements included HBV DNA level, HBV serology profiles, and transient elastography (TE). The cutoff for TE results included ≥5.9 kPa for F2-moderate fibrosis, ≥7.4 kPa for F3-severe fibrosis, and ≥9.6 kPa for F4-cirrhosis. Results: From March to December 2016, 15 HBV-HIV coinfected youths with a median duration on TDF-containing regimens of 3.3 years were enrolled. Five (33%) youths had significant liver fibrosis, 3 with F2-moderate, 1 with F3-advanced fibrosis, and 1 with F4-cirrhosis. Other 5 without liver fibrosis had hepatitis B surface e antigen (HBsAg) and hepatitis B surface e antigen (HBeAg) loss. Higher mean alanine transaminase (ALT) was observed among the group with F2-F4 when compared to those with F0. Conclusion: Liver fibrosis was evidenced in HBV-HIV coinfected youths in Thailand. Transient elastography might be considered for those who do not achieve HBsAg loss or have persistent ALT elevation while on treatment.

Alterations in subcortical brain structures have been reported in adults with HIV and, to a lesser extent, pediatric cohorts. The extent of longitudinal structural abnormalities in children with perinatal HIV infection (PaHIV) remains unclear. We modeled subcortical morphometry from whole brain structural magnetic resonance imaging (1.5 T) scans of 43 Thai children with PaHIV (baseline age = 11.09±2.36 years) and 50 HIV− children (11.26±2.80 years) using volumetric and surface-based shape analyses. The PaHIV sample were randomized to initiate combination antiretroviral treatment (cART) when CD4 counts were 15–24% (immediate: n = 22) or when CD4