A pilot program of HIV pre-exposure prophylaxis in Thai youth.

INTRODUCTION: There are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents. METHODS: This pilot study enrolled Thai adolescents 14-20 year-old without HIV who reported risk behaviour. All participants were offered daily tenofovir/emtricitabine (TDF-FTC) and followed for 24 weeks. HIV testing, renal function, bone density scan, and sexually transmitted infection (STI) testing including syphilis serology and urine molecular testing for gonorrhoea and C. trachomatis were performed at baseline and weeks 12 and 24. Adherence was evaluated through intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots. RESULTS: Of the 61 enrolled adolescents, median age 18.1 (IQR: 14.8-20.9) years, 46 (75.4%) were males and 36 (59%) were MSM. Retention to week 24 was 80.3%. One third (36%) had TFV-DP levels consistent with taking ≥6 pills/week at week 12 and 29% at week 24. The factors associated with taking ≥6 pills/week were being MSM (adjusted odds ratio [aOR]: 53.2, 95% CI: 1.6-1811; p = 0.027), presence of STI at baseline (aOR: 9.4, 95% CI: 1.5-58.5; p = 0.016), and self-report of decreased condom use while taking PrEP (aOR: 8.7, 95% CI: 1.4-56.6; p = 0.023). 31% had an STI at baseline and this declined to 18% at week 24. No renal or bone toxicity was observed and there were no HIV seroconversions. CONCLUSIONS: Daily oral PrEP with FTC-TDF in high-risk Thai adolescents is feasible, accepted, well-tolerated, and had no increased risk compensation; however, low adherence was a major challenge. Adolescent-specific PrEP strategies including long-acting modalities are needed for successful HIV prevention.

The effects of bivalent human papillomavirus (HPV) vaccination on high-risk anogenital HPV infection among sexually active female adolescents with and without perinatally acquired HIV.

BACKGROUND: Females with perinatal HIV (PHIV) infection are at elevated risk for anogenital high-risk human papillomavirus (HR-HPV) infection. Limited data are available around the effect of the HPV vaccination after initiation of sexual activity among PHIV youth. This study aims to assess the impact of a bivalent HPV vaccination on the persistence of anogenital HR-HPV among sexually active female PHIV youth and matched HIV-negative controls aged 12-24years in Thailand and Vietnam. METHODS: During a 3-year study, prevalent, incident, and persistent HR-HPV infection were assessed at annual visits. A subset of participants received a bivalent HPV vaccine. Samples were taken for HPV testing from the vagina, cervix, and anus. HR-HPV persistence was defined as the detection of the same genotype(s) at any anogenital compartment over≥two consecutive visits. RESULTS: Of the 93 PHIV and 99 HIV-negative female youth enrolled in this study, 25 (27%) PHIV and 22 (22%) HIV-negative youth received a HPV vaccine. Persistent infection with any HR-HPV type was significantly lower among PHIV youth who received the vaccine compared to those who did not (33%vs 61%, P =0.02); a difference was not observed among HIV-negative youth (35%vs 50%, P =0.82). PHIV infection (adjusted prevalence ratio [aPR] 2.31, 95% CI 1.45-3.67) and not receiving a HPV vaccine (aPR, 1.19, 95%CI 1.06-1.33) were associated with persistent anogenital HR-HPV infection. CONCLUSIONS: Bivalent HPV vaccination after initiation of sexual activity was associated with reduced persistence of anogenital HR-HPV infection in Southeast Asian PHIV female youth, which may be related to vaccine cross-protection. Primary and catch-up HPV vaccinations should be prioritised for children and youth with HIV.

Hybrid immunity from SARS-CoV-2 infection and mRNA BNT162b2 vaccine among Thai school-aged children.

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 < 0.001. Conclusions: Immune response that arises from BNT162b2 vaccine after natural infection and infection after 2 doses of BNT162b2 was higher than infection after partially-vaccinated children.

International Pediatric COVID-19 Severity Over the Course of the Pandemic.

Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children. Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 hospitalization during the stipulated time frame. Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy. Results: Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children. Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

Outcomes among Thai children with risk conditions hospitalized for pneumococcal disease (invasive or non-bacteraemic pneumonia): A multi-centre, observational study.

Objective: To describe the risk condition status and clinical outcomes among Thai children hospitalized with pneumococcal disease. Methods: In this retrospective analysis, children with invasive pneumococcal disease (IPD) or x-ray-confirmed non-bacteraemic pneumococcal pneumonia (NBPP) were identified from nine hospitals in Thailand between 2010 and 2019. Data on risk factors and outcomes were extracted from medical records. Results: In total, 413 cases were identified: 319 IPD and 94 NBPP. Overall, 133 (32.2%) patients were admitted to intensive care units and 11/406 (2.7%) died. Twenty-seven percent of IPD cases had at-risk conditions and 15% had high-risk conditions. Most IPD cases (32.9%) occurred in children aged 2-4 years, and most NBPP cases (28.7%) occurred in infants aged 0-11 months. Of 51 Streptococcus pneumoniae isolates collected, 41 (80%) were pneumococcal 13-valent conjugate vaccine serotypes. Only 5.1% of children had received a pneumococcal vaccine. Conclusions: Most children with IPD and NBPP did not have high-risk or at-risk conditions, while 42% had at-risk or high-risk conditions for pneumococcal disease. Very few children in the cohort had received any type of pneumococcal vaccine. Increasing the availability of pneumococcal conjugate vaccines should be considered to reduce the burden of pneumococcal disease among children in Thailand.

Immunogenicity and reactogenicity of heterologous COVID-19 vaccination in pregnant women.

This open-labeled non-inferiority trial evaluated immunogenicity and reactogenicity of heterologous and homologous COVID-19 vaccination schedules in pregnant Thai women. 18-45-year-old pregnant women with no history of COVID-19 infection or vaccination and a gestational age of ≥12 weeks were randomized 1:1:1 into three two-dose primary series scheduled 4 weeks apart: BNT162b2-BNT162b2 (Group 1), ChAdOx1-BNT162b2 (Group 2), and CoronaVac-BNT162b2 (Group 3). Serum antibody responses, maternal and cord blood antibody levels at delivery, and adverse events (AEs) following vaccination until delivery were assessed. The 124 enrolled participants had a median age of 31 (interquartile range [IQR] 26.0-35.5) years and gestational age of 23.5 (IQR 18.0-30.0) weeks. No significant difference in anti-receptor binding domain (RBD) IgG were observed across arms at 2 weeks after the second dose. Neutralizing antibody geometric mean titers against the ancestral Wuhan strain were highest in Group 3 (258.22, 95% CI [187.53, 355.56]), followed by Groups 1 (187.47, 95% CI [135.15, 260.03]) and 2 (166.63, 95% CI [124.60, 222.84]). Cord blood anti-RBD IgG was correlated with, and equal to or higher than, maternal levels at delivery (r = 0.719, P < .001) and inversely correlated with elapsed time after the second vaccination (r = -0.366, P < .001). No significant difference in cord blood antibody levels between groups were observed. Local and systemic AEs were mild-to-moderate and more frequent in Group 2. Heterologous schedules of CoronaVac-BNT162b2 or ChAdOx1-BNT162b2 induced immunogenicity on-par with BNT162b2-BNT162b2 and may be considered as alternative schedules for primary series in pregnant women in mRNA-limited vaccine settings.

The immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial.

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 <68% inhibition. The immunogenicity outcome was evaluated at 14 days after the second and third doses. RESULTS: During February to April 2022, 382 children with a median age (interquartile range) of 8.4 years (6.6-10.0) were enrolled. At 14 days, after two doses of BNT162b2, the geometric means of sVNT in 8-week vs 3-week interval groups were 49.6 (95% confidence interval [CI] 44.8-54.9) vs 16.5 (95% CI 13.0-20.9), with a geometric means ratio of 3.0 (95% CI 2.4-3.8). Among 102 participants who received the third dose at a median of 15 weeks from the second dose, the geometric means of sVNT increased to 73.3 (95% CI 69.0-77.8) and pseudovirus NT increased to 326 (95% CI 256-415). CONCLUSION: The extended 8-week interval regimen of BNT162b2 induced higher neutralizing antibodies than a standard 3-week interval regimen. The third dose induced high neutralizing antibodies against the Omicron variant.

A phase 3, multicenter, randomized, double-blind study to evaluate the interchangeability of V114, a 15-valent pneumococcal conjugate vaccine, and PCV13 with respect to safety, tolerability, and immunogenicity in healthy infants (PNEU-DIRECTION).

BACKGROUND: Pneumococcal disease (PD) remains a major health concern globally. In children, pneumococcal conjugate vaccines (PCVs) provide protection against PD from most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and public health important serotypes 22F and 33F. This phase 3 study evaluated safety and immunogenicity of mixed PCV13/V114 regimens using a 3 + 1 dosing schedule when changing from PCV13 to V114 at doses 2, 3, or 4. METHODS: 900 healthy infants were randomized equally to 5 intervention groups. PCVs were administered in a 3-dose infant series at 2, 4, and 6 months of age followed by a toddler dose at 12-15 months along with concomitant routine vaccines. Safety was evaluated as the proportion of participants with adverse events (AEs). Immunoglobulin G (IgG) responses to the 15 serotypes in V114 were measured at 30 days post-dose 3 and 30 days post-dose 4 (PD4). RESULTS: Frequencies of injection-site and systemic AEs were generally comparable across all intervention groups. At 30 days PD4 (primary endpoint), IgG geometric mean concentrations (GMCs) for the 13 shared serotypes were generally comparable between mixed V114/PCV13 and 4-dose regimens of PCV13 or V114. In mixed regimens at 30 days PD4, a toddler dose of V114 was sufficient to achieve IgG GMCs comparable to a 4-dose regimen of V114 for serotype 22F, while at least one infant dose was needed in addition to the toddler dose to achieve IgG GMCs comparable to a 4-dose regimen of V114 for serotype 33F. CONCLUSIONS: V114 was well tolerated with a generally comparable safety profile to PCV13. For 13 shared serotypes, both mixed regimens and the V114 4-dose regimen induced generally comparable antibody responses to 4-dose regimen with PCV13. Study results support interchangeability of V114 with PCV13 in infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03620162; EudraCT: 2018-001151-12.

The Outcomes of Transition from Pediatrics to Adult Care among Adolescents and Young Adults with HIV at a Tertiary Care Center in Bangkok.

Background: Adolescents and young adults with HIV (AYHIV) are at high-risk of loss to follow up and virologic failure, particularly during transition from pediatric to adult clinics. Methods: We reviewed the medical records of AYHIV to characterize retention and virologic suppression following their transition. Results: 101 AYHIV, 97% perinatally infected, were transferred at the median age of 20 (IQR: 19-21) years. At 1-year post-transition, 92.1% were retained in care and 73.3% had viral suppression and at 2-years the retention and viral suppression were 87.1% and 76.7%, respectively. Factors associated with viral suppression were transition at ≥ 20 years of age (aOR 4.38, 95% CI 1.41-13.65) and receiving first-line ART regimen, compared to second- or third-line regimens, at transition (aOR 6.05, 95% CI 1.55-23.58). Conclusion: Transition outcomes of AYHIV in our setting were suboptimal. There is a need for interventions to support AYHIV transition during this vulnerable period.

A phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of catch-up vaccination regimens of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants, children, and adolescents (PNEU-PLAN).

BACKGROUND: Despite widespread use of pneumococcal conjugate vaccines (PCVs) in children, morbidity and mortality caused by pneumococcal disease (PD) remain high. In addition, many children do not complete their PCV course on schedule. V114 is a 15-valent PCV that contains two epidemiologically important serotypes, 22F and 33F, in addition to the 13 serotypes present in PCV13, the licensed 13-valent PCV. METHODS: This phase III descriptive study evaluated safety and immunogenicity of catch-up vaccination with V114 or PCV13 in healthy children 7 months-17 years of age who were either pneumococcal vaccine-naïve or previously immunized with lower valency PCVs (NCT03885934). Overall, 606 healthy children were randomized to receive V114 (n = 303) or PCV13 (n = 303) via age-appropriate catch-up vaccination schedules in three age cohorts (7-11 months, 12-23 months, or 2-17 years). RESULTS: Similar proportions of children 7-11 months and 2-17 years of age reported adverse events (AEs) in the V114 and PCV13 groups. A numerically greater proportion of children 12-23 months of age reported AEs in the V114 group (79.0%) than the PCV13 group (59.4%). The proportions of children who reported serious AEs varied between different age cohorts but were generally comparable between vaccination groups. No vaccine-related serious AEs were reported, and no deaths occurred. At 30 days after the last PCV dose, serotype-specific immunoglobulin G geometric mean concentrations were comparable between vaccination groups for the 13 shared serotypes and higher in the V114 group for 22F and 33F. CONCLUSIONS: Catch-up vaccination with V114 in healthy individuals 7 months-17 years of age was generally well tolerated and immunogenic for all 15 serotypes, including those not contained in PCV13, regardless of prior pneumococcal vaccination. These results support V114 catch-up vaccination in children with incomplete or no PCV immunization per the recommended schedule.

Streptococcus pneumoniae Causing Invasive Diseases in Children and Adults in Central Thailand, 2012-2016.

Longitudinal data regarding the serotype distribution and antimicrobial susceptibility of S. pneumoniae-causing invasive pneumococcal disease (IPD) in developing countries are limited. Our aim was to monitor the antimicrobial susceptibility, serotype distribution, and serotype coverage rates of the pneumococcal conjugate vaccines (PCVs) and emerging non-vaccine serotypes (NVT) between 2012 and 2016 in central Thailand. Pneumococcal isolates from sterile specimens of patients, collected within a long-standing collaborative hospital network in central Thailand between 2012 and 2016, were studied. The pneumococcal serotypes included in the 15-valent PCV were identified by the quellung reaction, while the non-PCV15 serotypes were identified by multiplex PCR. Antimicrobial susceptibilities were determined by the microbroth dilution or disk diffusion method. Of the 276 pneumococcal isolates, 129 (46.7%) were from children aged ≤5 years. Only 9.0% of patients with available data received the PCV prior to the onset of the IPD. The most common vaccine serotypes were 6B (17.4%), 19A (13.0%), and 14 (11.2%), respectively. Non-PCV15 serotypes were detected in 27.9%; the most common serotypes were 15B/C (5.1%), 15A/F (4.0%), and 23A (3.6%), respectively. The serotype coverage rates of PCV10 in children aged ≤5 years was 55.8%, and 53.3% across all ages. PCV13 provided similar coverage rates to that of PCV15, 71.3% in children aged ≤5 years, and 72.1% across all ages. High susceptibilities to cefotaxime (94.6%), ofloxacin (98.2%), linezolid (99.6%), and vancomycin (100.0%) were observed, while the susceptibility to erythromycin (50.0%), TMP-SMZ (41.3%), and tetracycline (27.2%) were low. The susceptibilities to penicillin, meropenem, and clindamycin were 85.9%, 85.9%, and 84.8%, respectively. Serotype 19A was associated with a lower susceptibility than the non-19A isolates for penicillin (75.0% vs. 87.5%, p = 0.045), meropenem (52.8% vs. 90.8%, p < 0.001), erythromycin (33.3% vs. 53.8%, p = 0.022), and TMP-SMZ (16.7% vs. 45.0%, p = 0.001). Although the majority of the pneumococcal serotypes causing IPD in central Thailand were covered by the currently available PCVs, 25% of IPD were caused by NVT. Several emerging NVT identified were 15B/C, 15A/F, and 23A. The high rates of resistance to penicillin, meropenem, erythromycin, TMP-SMZ, and tetracycline observed is a major concern. Serotype 19A was associated with lower antimicrobial susceptibilities in comparison to the non-19A serotypes.

Immunogenicity and Reactogenicity of mRNA BNT162b2 COVID-19 Vaccine among Thai Adolescents with Chronic Diseases.

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.

Outcomes of Single-Dose Empirical Antibiotic Treatment in Children With Suspected Sepsis Implemented in the Emergency Department.

OBJECTIVES: Implementing a single-dose empirical antibiotic (SDEA) strategy at the emergency department (ED) in children with suspected sepsis may improve outcomes. We aim to evaluate the outcomes of the SDEA strategy for children with suspected sepsis at the ED in a tertiary care center in Bangkok. METHODS: Children who met the predefined checklist screening criteria for suspected sepsis were administered single-dose intravenous cefotaxime 100 mg/kg, or meropenem 40 mg/kg if they were immunocompromised or recently hospitalized. The medical records of children diagnosed with sepsis and septic shock caused by bacterial or organ-associated bacterial infections before and after implementation of the SDEA strategy were reviewed. RESULTS: A total of 126 children with sepsis before and 127 after implementation of the SDEA strategy were included in the analysis. The time from hospital arrival to antibiotic initiation was significantly reduced after implementation of the SDEA strategy: median, 241 (110-363) minutes before versus 89 (62-132) minutes after ( P < 0.001), with an increased number of patients starting antibiotics within 3 hours of hospital arrival: 42.1% vs 85.0% ( P < 0.001). Comparing before and after SDEA implementation, children receiving SDEA had a shorter median duration of antibiotic therapy: 7 (5-13.3) versus 5 (3-7) days ( P = 0.001), shorter length of hospital stay: 10 (6-16.3) versus 7 (4-11) days ( P = 0.001), and fewer intensive care unit admissions: 30 (23.8%) versus 17 (13.4%; P = 0.036); however, mortality was not different: 3 (2.4%) in both groups. In multivariate analysis, SDEA strategy was the independent factor associated with reduced intensive care unit admission or death. Adherence to SDEA was 91.4%. Single-dose empirical antibiotic was retrospectively considered not necessary for 22 children (11.9%), mostly diagnosed with viral infections afterward. CONCLUSIONS: Single-dose empirical antibiotic at the ED is an effective strategy to reduce the time from hospital arrival to antibiotic initiation and can help improve outcomes of sepsis in children.

Depression and Anxiety in Youth and Young Adults Living with HIV: Frequency and Associated Factors in Thai Setting.

Integrative mental health care in HIV patients is an important contributor to successful therapy. This is a cross-sectional study in youth and young adults who attend routine HIV clinic at a tertiary care centre in Bangkok. We recruited 100 youth and 130 young adults living with HIV to evaluate the frequency of depression and anxiety and associated sociodemographic including sexual orientation and health-related behaviours. Overall, about a fifth of the participants had significant depression or anxiety. Interestingly, we found different factors associated with depression in youth and young adults living with HIV. Loss of their father, loss of close relatives or friends, and being unemployed or school exclusion were the factors associate with depression in youth; while dangerous alcohol use, feeling discriminated against and having lipodystrophy were factors in young adults. The understanding of the frequency and different associated factors can inform more effective prevention and treatment strategies.

Immunogenicity of a Two-Dose Human Papillomavirus Vaccine Schedule in HIV-Infected Adolescents with Immune Reconstitution.

HIV-infected patients are at increased risk of human papillomavirus (HPV) acquisition and HPV-associated diseases. This study set out to determine whether a two-dose (2D) HPV vaccination schedule was sufficient in HIV-infected adolescents with immune reconstitution (IR) following antiretroviral treatment. Participants aged 9-15 years who had CD4 cell counts > 500 cells/mm3 and HIV-1 RNA < 40 copies/mL for at least one year were assigned to the 2D schedule, while older participants or those without IR received a three-dose (3D) schedule. Antibodies to HPV-16 and -18 were measured using a pseudovirion-based neutralization assay. A total of 96 subjects were enrolled; 31.3% and 68.7% received the 2D and 3D schedule, respectively. Of these, 66.7% and 57.6% of the 2D and 3D participants, respectively, were male. The seroconversion rates for HPV-16 and HPV-18 were 100% in all cases, except for HPV-18 in males who received the 3D schedule (97.4%). In males, the anti-HPV-16 geometric mean titers (GMTs) were 6859.3 (95% confidence interval, 4394.3-10,707.1) and 7011.1 (4648.8-10,573.9) in the 2D and 3D groups (p = 0.946), respectively, and the anti-HPV-18 GMTs were 2039.3 (1432.2-2903.8) and 2859.8 (1810.0-4518.4) in the 2D and 3D (p = 0.313) groups, respectively. In females, the anti-HPV-16 GMTs were 15,758.7 (8868.0-28,003.4) and 26,241.6 (16,972.7-40,572.3) in the 2D and 3D groups (p = 0.197), respectively, and the anti-HPV-18 GMTs were 5971.4 (3026.8-11,780.6) and 9993.1 (5950.8-16,781.1) in the 2D and 3D groups (p = 0.271), respectively. In summary, a 2D schedule is as immunogenic in young adolescents with IR as a 3D schedule in older subjects and those without IR.

Switching efavirenz to rilpivirine in virologically suppressed adolescents with HIV: a multi-centre 48-week efficacy and safety study in Thailand.

INTRODUCTION: Efavirenz (EFV) is commonly used for first-line antiretroviral therapy in children and adolescents with HIV, but is associated with neuropsychiatric and metabolic side effects. Rilpivirine (RPV) is better tolerated, and switching from EFV to RPV in virologically suppressed adults has been safe and efficacious, but data in adolescents are limited. Our primary objective was to describe the 48-week immunologic and virologic outcomes in virologically suppressed adolescents switching from EFV- to RPV-based antiretroviral therapy. Secondary objectives included assessment of neuropsychiatric adverse events, quality of life (QOL) and metabolic profiles while on RPV. METHODS: We conducted an open-label, single-arm, multi-centre study in Thailand in virologically suppressed adolescents aged 12-18 years receiving EFV plus two nucleoside/tide reverse transcriptase inhibitors (NRTIs/NtRTI) for ≥3 months. Participants were switched to an RPV (25 mg) tablet once daily, with the same NRTIs. HIV RNA viral load, CD4 cell count, fasting total cholesterol (TC), triglyceride, glucose, neuropsychiatric adverse events, depression and QOL were assessed over 48 weeks. Data were collected between February 2016 and September 2018. RESULTS: One hundred and two (52% male) adolescents were enrolled. Median age at entry was 15.5 years (IQR 14.4-17.0), median CD4 count was 664 cells/mm3 (29.9%); 58% were receiving tenofovir-DF and emtricitabine. At weeks 24 and 48, 96 (94.1%) and 94 (92.2%) participants were virologically suppressed, respectively, with no significant change in CD4 cell counts from baseline. Six (5.9%) participants experienced virologic failure, two of whom had RPV-associated mutations (K101E and Y181C) and a lamivudine-associated mutation (M184V/I). There were significant decreases in TC, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at weeks 24 and 48 and a significant increase in LDL/HDL ratio at week 48 compared to baseline. No substantial changes in EFV-related symptoms, depression score or health-related QOL were observed over time; however, there was significant improvement in performance-based assessments of executive function at week 24. CONCLUSIONS: A high proportion of adolescents (>92%) remained virologically suppressed up to 48 weeks after switching from EFV to RPV along with no significant change in CD4 cell counts. RPV was well tolerated and associated with improvements in metabolic profiles and executive function.

Invasive Fungal Diseases in Children with Acute Leukemia and Severe Aplastic Anemia.

Although the outcomes of childhood leukemia and severe aplastic anemia (SAA) have improved, infectious complications are still the major concern. Particularly worrisome are invasive fungal diseases (IFDs), one of the most common causes of infectious-related deaths in patients with prolonged neutropenia. A retrospective study was conducted of IFDs in pediatric patients with newly diagnosed or relapsed acute leukemia, or with SAA, at Siriraj Hospital, Mahidol University, Thailand. There were 241 patients: 150 with acute lymphoblastic leukemia (ALL), 35 with acute myeloid leukemia (AML), 31 with relapsed leukemia, and 25 with SAA. Their median age was 5.4 years (range, 0.3-16.0 years). The overall IFD prevalence was 10.7%, with a breakdown in the ALL, AML, relapsed leukemia, and SAA patients of 8%, 11.4%, 19.3%, and 16%, respectively. Pulmonary IFD caused by invasive aspergillosis was the most common, accounting for 38.5% of all infection sites. Candidemia was present in 34.6% of the IFD patients; Candida tropicalis was the most common organism. The overall case-fatality rate was 38.5%, with the highest rate found in relapsed leukemia (75%). The incidences of IFDs in patients with relapsed leukemia and SAA who received fungal prophylaxis were significantly lower than in those who did not (P = N/A and 0.04, respectively). IFDs in Thai children with hematological diseases appeared to be prevalent, with a high fatality rate. The usage of antifungal prophylaxes should be considered for patients with SAA to prevent IFDs.

Disseminated cryptococcosis in two boys with novel mutation of CD40 Ligand-Associated X-linked hyper-IgM syndrome.

X-linked hyper-IgM syndrome (XHIM) caused by CD40L mutations is a primary immunodeficiency condition that increases susceptibility to opportunistic infections. Disseminated cryptococcosis in XHIM is rarely reported in children. Here, we report two related boys who have a novel hemizygous frameshift c.208delC mutation of CD40L. They live in the western region of Thailand and developed disseminated cryptococcosis while receiving regular intravenous immunoglobulin supplementation.

Identification, Management, and Outcomes of Combination Antiretroviral Treatment Failure in Adolescents With Perinatal Human Immunodeficiency Virus Infection in Asia.

BACKGROUND: Combination antiretroviral therapy (cART) failure is a major threat to human immunodeficiency virus (HIV) programs, with implications for individual- and population-level outcomes. Adolescents with perinatally acquired HIV infection (PHIVA) should be a focus for treatment failure given their poorer outcomes compared to children and adults. METHODS: Data (2014-2018) from a regional cohort of Asian PHIVA who received at least 6 months of continuous cART were analyzed. Treatment failure was defined according to World Health Organization criteria. Descriptive analyses were used to report treatment failure and subsequent management and evaluate postfailure CD4 count and viral load trends. Kaplan-Meier survival analyses were used to compare the cumulative incidence of death and loss to follow-up (LTFU) by treatment failure status. RESULTS: A total 3196 PHIVA were included in the analysis with a median follow-up period of 3.0 years, of whom 230 (7.2%) had experienced 292 treatment failure events (161 virologic, 128 immunologic, 11 clinical) at a rate of 3.78 per 100 person-years. Of the 292 treatment failure events, 31 (10.6%) had a subsequent cART switch within 6 months, which resulted in better immunologic and virologic outcomes compared to those who did not switch cART. The 5-year cumulative incidence of death and LTFU following treatment failure was 18.5% compared to 10.1% without treatment failure. CONCLUSIONS: Improved implementation of virologic monitoring is required to realize the benefits of virologic determination of cART failure. There is a need to address issues related to accessibility to subsequent cART regimens, poor adherence limiting scope to switch regimens, and the role of antiretroviral resistance testing.