Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children.

BACKGROUND: Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). METHODS: We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed. RESULTS: From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01). CONCLUSIONS: In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).

Long-term risk of mortality and loss to follow-up in children and adolescents on antiretroviral therapy in Asia.

OBJECTIVE: We described mortality and loss to follow-up (LTFU) in children and adolescents who were under care for more than 5 years following initiation of antiretroviral therapy (ART). METHODS: Patients were followed from 5 years after ART until the earlier of their 25th birthday, last visit, death, or LTFU. We used Cox regression to assess predictors of mortality and competing risk regression to assess factors associated with LTFU. RESULTS: In total, 4488 children and adolescents initiating ART between 1997 and 2016 were included in the analysis, with a median follow-up time of 5.2 years. Of these, 107 (2.2%) died and 271 (6.0%) were LTFU. Mortality rate was 4.35 and LTFU rate 11.01 per 1000 person-years. Increased mortality was associated with AIDS diagnosis (adjusted hazard ratio [aHR] 1.71; 95% confidence interval [CI] 1.24-2.37), current CD4 count <350 cells/mm3 compared with ≥500 (highest aHR 13.85; 95% CI 6.91-27.76 for CD4 <200), viral load ≥10 000 copies/mL compared with <400 (aHR 3.28; 95% CI 1.90-5.63), and exposure to more than one ART regimen (aHR 1.51; 95% CI 1.14-2.00). Factors associated with LTFU were male sex (adjusted subdistribution hazard ratio [asHR] 1.29; 95% CI 1.04-1.59), current viral load >1000 copies/mL compared with <400 (highest asHR 2.36; 95% CI 1.19-4.70 for viral load 1000-9999), and ART start after year 2005 compared with ≤2005 (highest asHR 5.96; 95% CI 1.98-17.91 for 2010-2016). CONCLUSION: For children and adolescents surviving 5 years on ART, both current CD4 and viral load remained strong indicators that help to keep track of their treatment outcomes. More effort should be made to monitor patients who switch treatments.

High mortality in adolescents and young adults with perinatally-acquired HIV in Thailand during the transition to adulthood.

Transitioning from pediatric to adult care remains a challenge for adolescents and young adults with perinatally-acquired HIV (AYA-PHIV). We assessed treatment outcomes and mortality among Thai AYA-PHIV. The study included AYA-PHIV who reached age 18-24 years who started antiretroviral treatment during childhood at five pediatric HIV clinics across Thailand. From November 2020-July 2021, data were gathered from a cohort database, medical records, and the Thai National AIDS Program. Of 811 eligible AYA-PHIV, 93% were alive; median age 22.3 years (IQR 20.6-23.7), treatment duration 16.1 years (IQR 13.4-18.0). Current HIV care was provided in adults (71%) and pediatric clinics (29%). Treatment regimens included non-nucleoside reverse transcriptase inhibitors (55%), protease inhibitors (36%), and integrase inhibitors (8%); 78% had HIV RNA <200 copies/ml. Of the 7.0% who died, median age at death was 20.8 years (IQR 20.6-22.1); 88% were AIDS-related death. Mortality after age 18 was 1.76 per 100-person years (95% confidence interval 1.36-2.28). Those with CD4 <200 cell/mm3 at age 15 had higher risk of mortality (adjusted hazard ratio 6.16, 95% CI 2.37-16.02). In conclusion, the high mortality among Thai AYA-PHIV indicated the need for better systems to support AYA-PHIV during the transition to adulthood.

Pregnancy and birth outcomes among young women living with perinatally acquired HIV in Thailand and Vietnam.

We conducted a retrospective cohort study of pregnancy and infant outcomes in 670 adolescents and young adult women with perinatally acquired HIV (AYAPHIV), aged 15-24 years, in Thailand and Vietnam. Between January 2013 and December 2018, there were 52 pregnancies, for an incidence of 2.49 (95% CI 1.90-3.27) per 100 person-years. The median age at pregnancy was 17.7 years (IQR 16.8-18.9). Pregnant AYAPHIV had been on cART for a lifetime median of 9.8 years (IQR 7.3-12.4). At the time of conception, the median CD4 was 521 cells/mm3 (IQR 213-760), and 76% had HIV RNA ≤400 copies/ml. Of the 51 pregnancies with available outcomes, 90% resulted in live singleton births at a median gestational age of 38 weeks (IQR 37-39); 77% of mothers (n = 27/35) had HIV RNA ≤400 copies/ml at delivery. Among infants with available data, 50% (n = 21/42) were male and 29% (n = 12/42) were reported to be low birthweight (<2,500gm); none (n = 0/41) were breastfed. One infant was diagnosed with HIV. Our findings emphasize that efforts to strengthen reproductive health education, including contraception, pregnancy-related psychosocial support services, and prevention of vertical HIV transmission interventions, in our region are needed for adolescents with perinatally acquired HIV as they transition to young adults.

Disclosure of HIV status and associated clinical outcomes of children and adolescents living with HIV in Asia.

Disclosure of HIV status is an important part of pediatric care. We studied disclosure and clinical outcomes in a multi-country Asian cohort of children and adolescents with HIV. Those 6-19 years of age who initiated combination antiretroviral therapy (cART) between 2008 and 2018, and who had at least one follow-up clinic visit were included. Data up to December 2019 were analyzed. Cox and competing risk regression analyses were used to assess the effect of disclosure on disease progression (WHO clinical stage 3 or 4), loss to follow-up (LTFU; > 12 months), and death. Of 1913 children and adolescents (48% female; median [IQR] age 11.5 [9.2-14.7] years at last clinic visit), 795 (42%) were disclosed to about their HIV status at a median age of 12.9 years (IQR: 11.8-14.1). During follow-up, 207 (11%) experienced disease progression, 75 (3.9%) were LTFU, and 59 (3.1%) died. There were lower hazards of disease progression (adjusted hazard ratio [aHR] 0.43 [0.28-0.66]) and death (aHR 0.36 [0.17-0.79]) for those disclosed to compared with those who were not. Disclosure and its appropriate implementation should be promoted in pediatric HIV clinics in resource-limited settings.

Global COVID-19 Vaccination in Infants and Children: Effectiveness, Safety, and Challenges.

COVID-19 Vaccines, which include mRNA and inactivated vaccines, have been proven effective and safe for infants and children aged more than six months in reducing the severity of the disease, hospitalization, multisystem inflammatory syndrome in children, and death. Nonetheless, the real-world effectiveness of these vaccines in preventing infection is generally lower than in clinical trials due to the emergence of variants of concern, especially the Omicron strains. Despite the availability of vaccines for children, their uptake remains low globally, particularly among parents who are hesitant to vaccinate their children. This review article aims to provide a comprehensive overview of COVID-19 vaccine safety and efficacy from clinical trials and the current COVID-19 vaccine recommendations for infants and children aged 6 months to < 12 years for 2023-2024, discuss the progress made in vaccine implementation and real-world effectiveness, and address the knowledge gap and future directions.

Incidence of Respiratory Syncytial Virus Lower Respiratory Tract Infections During the First 2 Years of Life: A Prospective Study Across Diverse Global Settings.

BACKGROUND: The true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data on RSV-LRTI incidence and burden in the first 2 years of life. METHODS: This prospective, observational cohort study was conducted in Argentina, Bangladesh, Canada, Finland, Honduras, South Africa, Thailand, and United States. Children were followed for 24 months from birth. Suspected LRTIs were detected via active (through regular contacts) and passive surveillance. RSV and other viruses were detected from nasopharyngeal swabs using PCR-based methods. RESULTS: Of 2401 children, 206 (8.6%) had 227 episodes of RSV-LRTI. Incidence rates (IRs) of first episode of RSV-LRTI were 7.35 (95% confidence interval [CI], 5.88-9.08), 5.50 (95% CI, 4.21-7.07), and 2.87 (95% CI, 2.18-3.70) cases/100 person-years in children aged 0-5, 6-11, and 12-23 months. IRs for RSV-LRTI, severe RSV-LRTI, and RSV hospitalization tended to be higher among 0-5 month olds and in lower-income settings. RSV was detected for 40% of LRTIs in 0-2 month olds and for approximately 20% of LRTIs in older children. Other viruses were codetected in 29.2% of RSV-positive nasopharyngeal swabs. CONCLUSIONS: A substantial burden of RSV-LRTI was observed across diverse settings, impacting the youngest infants the most. Clinical Trials Registration. NCT01995175.

Short-term immune response after inactivated SARS-CoV-2 (CoronaVac®, Sinovac) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-AstraZeneca) vaccinations in health care workers.

BACKGROUND: Inactivated SARS-CoV-2 (CoronaVac®, Sinovac, or SV) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-Astra Zeneca, or AZ) vaccines have been administered to the health care workers (HCWs). OBJECTIVE: To determine the short-term immune response after the SV and AZ vaccinations in HCWs. METHODS: In this prospective cohort study, HCWs who completed a 2-dose regimen of the SV or AZ were included. Immune response was evaluated by surrogate viral neutralization test (sVNT) and anti-SARS-CoV-2 total antibody. Blood samples were analyzed at 4 and 12 weeks after the complete vaccination. The primary outcome was the seroconversion rate at 4-weeks after complete immunization. RESULTS: Overall, 185 HCWs with a median (IQR) age of 40.5 (30.3-55.8) years (94 HCWs in the SV group and 91 in the AZ group) were included. At 4 weeks after completing the SV vaccination, 60.6% (95%CI: 50.0-70.6%) had seroconversion evaluated by sVNT (≥ 68% inhibition), comparable to the patients recovered from mild COVID-19 infection (69.0%), with a rapid reduction to 12.2% (95%CI: 6.3-20.8) at 12 weeks. In contrast, 85.7% (95%CI: 76.8-92.2%) HCWs who completed two doses of the AZ for 4 weeks had seroconversion, comparable to the COVID-19 pneumonia patients (92.5%), with a reduction to 39.2% (95%CI: 28.4-50.9%) at 12 weeks. When using the anti-SARS-CoV-2 total antibody level (≥ 132 U/ml) criteria, only 71.3% HCWs in the SV group had seroconversion, compared to 100% in the AZ group at 4 weeks. CONCLUSIONS: A rapid decline of short-term immune response in the HCWs after the SV vaccination indicates the need for a vaccine booster, particularly during the ongoing spreading of the SARS-CoV-2 variants of concern.

Impact of Vitamin D and Calcium Supplementation on Bone Mineral Density and Bone Metabolism Among Thai Adolescents With Perinatally Acquired Human Immunodeficiency Virus (HIV) Infection: A Randomized Clinical Trial.

BACKGROUND: To evaluate the impact of vitamin D and calcium supplementation (VitD/Ca) on lumbar spine bone mineral density (LSBMD) and bone metabolism among Thai adolescents with perinatally acquired HIV (PHIVA). METHODS: A multicenter, randomized, active-control, open-labeled trial was conducted. PHIVA (aged 10-20 years) who were on stable cART were enrolled. Baseline LSBMD status was defined as low (z-score ≤ -2) and normal (> -2). Eligible PHIVA were randomly assigned to receive standard-dose (400 IU/1200 mg/day) or high-dose (400 IU/1200 mg/day plus ergocalciferol 20 000 IU/week) VitD/Ca supplementation for 48 weeks (ratio 1:1, stratified by baseline LSBMD). Study outcomes were changes in LSBMD, LSBMD z-scores, and bone metabolism-related biomarkers (25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone [iPTH], C-terminal telopeptide [CTX], procollagen type I amino-terminal propeptide [PINP]) from baseline to week 48. RESULTS: Among 200 enrolled PHIVA, median age was 16 (IQR:14-18) years; 61% were on NNRTI-based cART. Median 25(OH)D level was 25.5 (IQR: 20.8-33.0) ng/mL. After 48-week VitD/Ca supplementation, LSBMD significantly increased in both treatment groups (high-dose: median: +0.07 [IQR: +0.04 to +0.11] g/cm2; P < .001; standard-dose: +0.09 [+0.03 to +0.13] g/cm2; P < .001). Notably, the change in LSBMD z-scores was significantly greater in high-dose versus standard-dose groups (median: +0.4 [IQR: -0.1 to +0.9] vs +0.1 [-0.4 to +0.7]; P = .02). Levels of 25(OH)D increased, whereas iPTH, CTX, and PINP declined significantly in both groups (P < .05), but no between-group differences were demonstrated. CONCLUSIONS: Over 48-week VitD/Ca supplementation, significant increases in LSBMD, and significant decreases in bone metabolism-related markers were observed among our Thai PHIVA in both treatment groups. The improvement in LSBMD z-score was more enhanced with high-dose VitD/Ca supplementation than standard-dose. High-dose VitD/Ca supplementation might be considered to promote bone health in this population. CLINICAL TRIALS REGISTRATION: NCT02426840.

Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy Since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected With Human Immunodeficiency Virus.

BACKGROUND: Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown. METHODS: We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings. RESULTS: Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P < .020 and P < .001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P < .01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during 3 years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARVs before starting ART and those who delayed ART initiation without receiving prior prophylaxis. CONCLUSIONS: Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir.

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.

Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

BACKGROUND: Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin. METHODS: In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). RESULTS: From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29). CONCLUSIONS: In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).

ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing.

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 < 14 kg while dosing was in development. METHODS: ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks. RESULTS: Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9-18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weighing ≥35 kg in ODYSSEY A and extending recruitment (above 700) to allow for ≥60 additional children weighing between 3 to < 14 kg with associated PK; (iv) a safety alert associated with DTG use during pregnancy, which required a review of the safety plan for adolescent girls. CONCLUSIONS: By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. TRIAL REGISTRATION: NCT, NCT02259127 , registered 7th October 2014; EUDRACT, 2014-002632-14, registered 18th June 2014 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES ); ISRCTN, ISRCTN91737921 , registered 4th October 2014.

Acceptance and outcome of interventions in a meropenem de-escalation antimicrobial stewardship program in pediatrics.

BACKGROUND: Prospective audit and feedback is a method that allows the antimicrobial stewardship program (ASP) team to interact with attending physicians to tailor antibiotic therapy, including de-escalation, as appropriate. This study aimed to evaluate the acceptance and outcomes of ASP de-escalation recommendations in children who received meropenem. METHODS: A prospective cohort study was conducted in children aged 1 month to 18 years who received meropenem in a tertiary-care teaching hospital. The ASP team gave recommendation between 72 and 120 h after initiating meropenem therapy. Acceptance of de-escalation recommendations among primary physicians was evaluated within 24 h of recommendation. Outcomes included clinical success rate on the 7th day and incidence rate of acquisition of carbapenem-resistant gram-negative bacteria (CR-GNB) within 30 days. RESULTS: From March to December 2019, 217 children with a median (interquartile range) age of 2.1 (0.6, 9.5) years received meropenem. The ASP team gave recommendations in 127 (58.5%) of cases for continuation of meropenem therapy and 90 (41.5%) of cases for de-escalation. The overall acceptance of ASP de-escalation recommendations was 57.8% (95%CI: 46.9-68.1%). Clinical success rates were 85.2% in the accepted group compared to 77.5% in the rejected group (P = 0.06). The incidence rate of acquisition of CR-GNB within 30 days after treatment was 5.8% in the accepted group and 15.8% in the rejected group (P = 0.03). CONCLUSIONS: About half of the recommendations to de-escalate meropenem prescriptions were accepted through the ASP intervention. Carbapenem-resistant gram-negative bacteria acquisitions was less likely in the de-escalation group. A robust de-escalation strategy 72 h following carbapenem initiation should be encouraged to combat multidrug-resistant organisms.

Adaptation of a Theory-Based Social Networking and Gamified App-Based Intervention to Improve Pre-Exposure Prophylaxis Adherence Among Young Men Who Have Sex With Men in Bangkok, Thailand: Qualitative Study.

BACKGROUND: HIV 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. OBJECTIVE: This 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. METHODS: We 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. RESULTS: For 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. CONCLUSIONS: The 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 REGISTRATION: ClinicalTrials.gov NCT04413708; http://clinicaltrials.gov/ct2/show/NCT04413708.

Behavioral problems in perinatally HIV-infected young children with early antiretroviral therapy and HIV-exposed uninfected young children: prevalence and associated factors.

Although behavioral problems have been observed in children and adolescents with perinatally-acquired HIV infection (PHIV), behavioral information regarding younger PHIV children are scarce. This study aims to identify behavioral problems in PHIV and HIV-exposed uninfected (HEU) children and to evaluate factors associated with such problems. A prospective study of PHIV and HEU young children was conducted. Behavioral problems were assessed with the Child Behavior Checklist (CBCL) at baseline and 12 months later among children aged 18-60 months old. The Patient Health Questionnaire-9 and the Parenting Styles & Dimensions Questionnaire identified primary caregivers' symptoms of depression and parenting styles, respectively, at both visits. Chi-squared analyses were used to compare the prevalence of behavioral problems between groups. Factors associated with behavioral problems were analyzed by logistic regression. From 2016 to 2017, 121 children (41 PHIV and 80 HEU) were assessed with no significant differences in prevalence of Total, Internalizing, Externalizing, and Syndrome scales problems between PHIV and HEU at both visits (p > 0.5). Primary caregivers' depression and lower education in addition to authoritarian and permissive parenting styles were significantly related to child behavioral problems. Family-centered care for families affected by HIV, including positive parenting promotion, mental health care, and education are warranted.

Husband's willingness-to-pay for HIV and syphilis screening at antenatal care clinic under the Thai universal coverage scheme.

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 »SD 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.

Antimicrobial prescription patterns in a tertiary-care pediatric unit in Thailand.

BACKGROUND: Antimicrobial resistance is one of the greatest public health threats worldwide. The improper prescription of antibiotics is one factor that promotes antibiotic resistance. Access to antimicrobial surveillance data is essential when assessing the pattern and appropriateness of antimicrobial prescriptions in hospitals and for the establishment of an antimicrobial stewardship program. This study aimed to describe the rate of antimicrobial use and the pattern of prescriptions in a tertiary care pediatric unit in Thailand. METHODS: A point prevalence survey on antimicrobial use was conducted monthly between January and June 2016, using standardized tools. The survey included all inpatient pediatric beds and identified all children receiving antimicrobial treatment on the day of the survey. RESULTS: The study included 644 children, 43.3% of whom received antimicrobial treatment during hospitalization. In general wards, the rate of antimicrobial prescriptions was 37.2%; in oncology wards it was 47.0%; in intensive care units it was 38.7%, and in surgical wards it was 67.7%. Meropenem was the most prescribed antimicrobial in the general wards (24.5%) and intensive care units (28.6%), whereas antipseudomonas was the most commonly prescribed antimicrobial in the oncology ward (26.6%). For the surgical ward, the most prescribed antimicrobial was third-generation cephalosporin for both prophylaxis and treatment (39.0%). The most common reason for antimicrobial use was the treatment of infections. CONCLUSIONS: Nearly half of hospitalized children received at least one antimicrobial. This was comparable with other pediatric tertiary care centers, although the high use of meropenem was different. This study provides important baseline information on antimicrobial use in a large tertiary-care pediatric unit and could lead to a nationwide survey in the future.

Gaps in the elimination of congenital syphilis in a tertiary care center in Thailand.

BACKGROUND: The World Health Organization has set a goal to eliminate mother-to-child transmission of syphilis to a target of <50 cases per 100 000 live births. This study aimed to determine the rate of congenital syphilis and identify gaps in prevention. METHODS: A retrospective chart review was conducted in a tertiary care center in Bangkok, Thailand. The study included all pregnant women with positive syphilis serology and their infants. All congenital syphilis cases were categorized according to Centers for Disease Control criteria. RESULTS: From 2013 to 2017, 69 syphilis-infected pregnant women were included, with 30 congenital syphilis cases. The rate of congenital syphilis was 115 cases (95% CI 78-164) per 100 000 live births. The median (interquartile range) maternal age was 21 (18-32) years and 12 (17%) women had human immunodeficiency virus co-infection. Regarding maternal treatment, 28 (41%) women had inadequate treatment due to 13 cases (19%) of late or no antenatal care, six cases (8%) of recent infection near delivery, five cases (7%) of failure of treatment provision, and four (6%) others. There were three syphilitic stillbirths who were prematurely born to untreated pregnant women and 67 live births (one set of twins) of which 27 met definitions of probable congenital syphilis. They received complete treatment with penicillin and had non-reactive rapid plasma reagin within the first 6 months of life, with the exception of one who had non-reactive rapid plasma reagin at the age of 7 months. CONCLUSIONS: Congenital syphilis remains a problem in our setting. Nearly half of pregnant women who had syphilis had inadequate treatment. There is an urgent need to strengthen diagnosis and the treatment cascade of syphilis during antenatal care.