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Objective: Dolutegravir (DTG) is recommended globally for people living with HIV. The present study aimed to describe the efficacy and safety of DTG-based regimens among youth aged 18 to 24 years. Materials and Methods: A retrospective cohort study was conducted among youth aged 18 to 24 years living with HIV at Chulalongkorn Hospital. Participants were divided into antiretroviral naïve (AN), antiretroviral experienced with treatment failure (AETF), and antiretroviral experienced and virally suppressed (AEVS). DTG was prescribed as a daily individual tablet or as part of a fixed-dose combination. The primary outcome was virological suppression defined as VL of less than 200 copies/mL within 12 months after DTG initiation. Secondary outcomes included body weight and lipid profile changes. Results: Between 2017 and 2022, 87 youth with a median age of 20.6 (IQR 19.6 to 21.9) years were initiated on DTG. Fifty-six (64.3%) were male. Twelve participants were AN, 18 were AETF, and 57 were AEVS. HIV viral suppression was 100% and 96.2% among those AN and AEVS respectively, but only 54.5% amongst the AETF group (p<0.001). CD4 lymphocyte counts increased in all groups at follow-up. Median body weight change was +0.4 (IQR -1.8 to 3.6) kg in males and +0.5 (IQR -2.8 to 1.7) kg in females. Median total cholesterol declined from 167 (IQR 142 to 186) to 152 (IQR 135 to 170) mg/dL, p=0.003. Median triglycerides declined from 83 (IQR 60 to 129) to 66 (IQR 46 to 78), p<0.001. No hospitalizations or mortalities were observed in the study. Conclusion: DTG was effective and well-tolerated in youth living with HIV, with no significant weight gain and improved lipid profiles. DTG implementation among youth living with HIV should be continued. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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 10copies/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

• A colistin loading dose versus a standard initial dose in paediatric patients was compared. • Plasma colistin concentrations were measured by liquid chromatography–tandem mass spectrometry. • A full pharmacokinetic (PK) analysis was performed and PK parameters were compared. • A colistin loading dose resulted in greater optimisation of PK parameters. • No increase in the rate of acute kidney injury was observed with a loading dose. Use of colistin in children is rising in line with the increase of multidrug-resistant Gram-negative bacteria (MDR-GNB). In adults, a colistin loading dose is recommended to achieve therapeutic concentrations within 12–24 h. Here we aimed to describe the pharmacokinetic (PK) parameters of a loading dose versus a recommended initial dose of intravenous colistimethate sodium (CMS) in paediatric patients. A prospective, open-label, PK study was conducted in paediatric patients (age 2–18 years) with normal renal function. Patients (n = 20) were randomly assigned to receive either a CMS loading dose (LD group) of 4 mg of colistin base activity (CBA)/kg/dose or a standard initial dose (NLD group) of 2.5 mg (12-h interval) or 1.7 mg (8-h interval) of CBA/kg/dose. Serial blood samples were collected. Plasma concentrations of formed colistin were measured by LC-MS/MS. PK parameters were reported. Acute kidney injury (AKI) was monitored by serum creatinine and urine NGAL. The median (interquartile range) age and body weight were 8.5 (3.5–11.3) years and 21.5 (13.5–20.0) kg. The mean (standard deviation) of first-dose PK parameters of the LD group versus the NLD group were: C max , 6.1 (2.4) vs. 4.1 (1.3) mg/L; AUC 0– t , 26.5 (12.5) vs. 13.5 (3.6) mg/L·h; V d , 0.7 (0.4) vs. 0.6 (0.3) L/kg; and t 1/2 , 2.9 (0.6) vs. 2.6 (0.4) h. No patient developed AKI by serum creatinine criteria. A CMS loading dose is beneficial for improvement of colistin exposure without increased AKI. A higher daily dose of CMS should be considered, especially for MDR-GNB treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: HIV-infected children have high risk of invasive pneumococcal disease (IPD) despite receiving highly active antiretroviral therapy (HAART). This study aimed to determine the immunogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV-7) in Thai HIV-infected children compared to HIV-exposed uninfected children. Methods: A prospective study was conducted among children 2 months to 9 years. The number of PCV-7 doses depended upon age and HIV status; 2–6 months of age: 3 doses; 7–23 months of age: 2 doses; HIV-infected child ≥24 months: 2 doses and HIV-exposed child ≥24 months: 1 dose. Serotype-specific pneumococcal IgG antibody concentrations were measured at baseline and 28 days after complete vaccination. The primary end point was the proportion of children who achieved serotype-specific IgG antibody concentration at a cut off level ≥0.35μg/mL. Secondary end points were a 4-fold increase in serotype-specific IgG antibody, rates of adverse events and predictors for seroconversion among HIV-infected children. Results: Fifty-nine HIV-infected and 30 HIV-exposed children were enrolled. The median (IQR) age was 97 (67–111) and 61 months (51–73), respectively (p <0.001). Among HIV-infected children, current and nadir CD4 counts were 1079cell/mm3 and 461cell/mm3, respectively. The proportion of children who achieved pneumococcal IgG ≥0.35μg/mL was in the range of 85–98% in HIV-infected and 83–100% in HIV-exposed children depending on serotype. The lowest response was to serotype 6B in both groups. The 4-fold increase in serotype-specific IgG concentrations was similar between HIV-infected and HIV-exposed groups, except for serotype 9V (p =0.027). HIV-infected children who had a history of AIDS had a lower antibody response to serotype 23F (p =0.025). Seven (12%) HIV-infected children had a grade 3 local reaction. Conclusion: PCV-7 is highly immunogenic and safe among HIV-infected children treated with HAART. The use of the pneumococcal conjugate vaccine among HIV-infected children is encouraged in order to prevent IPD. [Copyright &y& Elsevier]

Background: Lopinavir/ritonavir (LPV/r) is an effective and commonly used protease inhibitor in HIV-infected adolescents. Previous data showed high plasma concentrations of LPV in Thai patients. This study determined the pharmacokinetic (PK) parameters of a low-dose LPV/r tablet (70% of standard dose) in HIV-infected Thai adolescents., Methods: A total of 24 adolescents on LPV/r-containing HAART regimens with HIV RNA<50 copies/ml were included. Standard and low doses for two different weight bands using LPV/r 100/25 mg tablet formulation twice daily were prescribed as follows: 3 and 2 tablets for adolescents weighing 25-35 kg, and 4 and 3 tablets for those weighing >35 kg, respectively. On the fourth week of treatment, PK was performed for all doses at 0 (pre-dose), 2, 4, 6, 8, 10 and 12 h. LPV and ritonavir concentrations were measured using the HPLC method., Results: The median (IQR) age was 13.5 (12-15) years. The median LPV doses of standard and low doses were 290 and 208 mg/m(2). The mean (sd) area under the concentration-time curve at 0-12 h, maximum concentration and plasma concentration at 12 h for the standard dose were 97.6 (25.7) mg•h/l, 11.1 (2.6) mg/l and 4.1 (2.0) mg/l, and for the low dose were 87.4 (29.0) mg•h/l, 11.0 (3.1) mg/l and 3.2 (1.9) mg/l, respectively. No significant differences were detected between the groups. One child had plasma concentration at 12 h <1.0 mg/l while on low-dose LPV/r but HIV RNA was undetectable., Conclusions: The low-dose LPV/r tablet provides adequate PK parameters in HIV-infected Thai adolescents. A randomized study to assess the efficacy of low and standard doses of LPV/r among Thai HIV-infected adolescents should be explored.

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%<15% at baseline or decrease in CD4 count ≥30% from baseline. VF was defined as HIV-RNA>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.