Pharmacokinetics of Generic Pediatric Dolutegravir Dispersible Tablet in Thai Young Children Living With HIV Weighing Below Twenty Kilograms.

INTRODUCTION: Dolutegravir (DTG) dispersible tablet (DTG-DT) is a pediatric-friendly formulation. We aimed to describe the pharmacokinetics and virologic responses of generic DTG-DT in children weighing <20 kg. METHODS: Children living with HIV-1 and <7 years of age weighing 6 to <20 kg were eligible. A generic 10-mg scored DTG-DT was administered to children using 3 weight bands (WB): WB1 (6 to <10 kg), WB2 (10 to <14 kg) and WB3 (14 to <20 kg), at doses of 20 mg (higher than World Health Organization recommendation of 15 mg), 20 mg and 25 mg, respectively. Steady-state intensive pharmacokinetics (PK) was performed in fasting condition with blood sampling at predose and 1, 2, 3, 4, 6 and 24 hours postdose. DTG PK parameters were estimated using a noncompartmental analysis, and DTG trough concentrations (C 24 ) and 24-hour area under the concentration-time curve were calculated. Comparisons were made with ODYSSEY and IMPAACT 2019. And 90% effective concentration of 0.32 mg/L was used as a reference individual DTG C 24 concentration. RESULTS: From August 2021 to March 2023, 29 Thai children with a median (interquartile range) age of 3.2 (1.5-4.8) years were enrolled; 8 in WB1, 9 in WB2 and 12 in WB3. All children were treatment experienced and 59% had HIV RNA <200 copies/mL. Overall geometric mean (coefficient of variation percentage) DTG C 24 was 1.0 (46%) mg/L [WB1, 0.9 (53%); WB2, 0.9 (27%); WB3, 1.2 (51%)]. Geometric mean (coefficient of variation percentage) 24-hour area under the concentration-time curve was 83.2 (24%) mg h/L [WB1, 84.3 (31%); WB2, 76.9 (16%); WB3, 87.6 (25%)]. At weeks 24 and 48, 90% and 92% of participants had plasma HIV RNA <200 copies/mL. CONCLUSIONS: Generic DTG-DT provided adequate drug exposure in children weighing 6 to <20 kg. The exploratory dose of DTG 20 mg for children weighing 6 to <10 kg showed similar PK parameters to World Health Organization doses in the other WB.

Pharmacokinetics of Generic Pediatric Dolutegravir Dispersible Tablet in Thai Young Children Living With HIV Weighing Below Twenty Kilograms.

INTRODUCTION: Dolutegravir (DTG) dispersible tablet (DTG-DT) is a pediatric-friendly formulation. We aimed to describe the pharmacokinetics and virologic responses of generic DTG-DT in children weighing <20 kg. METHODS: Children living with HIV-1 and <7 years of age weighing 6 to <20 kg were eligible. A generic 10-mg scored DTG-DT was administered to children using 3 weight bands (WB): WB1 (6 to <10 kg), WB2 (10 to <14 kg) and WB3 (14 to <20 kg), at doses of 20 mg (higher than World Health Organization recommendation of 15 mg), 20 mg and 25 mg, respectively. Steady-state intensive pharmacokinetics (PK) was performed in fasting condition with blood sampling at predose and 1, 2, 3, 4, 6 and 24 hours postdose. DTG PK parameters were estimated using a noncompartmental analysis, and DTG trough concentrations (C24) and 24-hour area under the concentration-time curve were calculated. Comparisons were made with ODYSSEY and IMPAACT 2019. And 90% effective concentration of 0.32 mg/L was used as a reference individual DTG C24 concentration. RESULTS: From August 2021 to March 2023, 29 Thai children with a median (interquartile range) age of 3.2 (1.5-4.8) years were enrolled; 8 in WB1, 9 in WB2 and 12 in WB3. All children were treatment experienced and 59% had HIV RNA <200 copies/mL. Overall geometric mean (coefficient of variation percentage) DTG C24 was 1.0 (46%) mg/L [WB1, 0.9 (53%); WB2, 0.9 (27%); WB3, 1.2 (51%)]. Geometric mean (coefficient of variation percentage) 24-hour area under the concentration-time curve was 83.2 (24%) mg h/L [WB1, 84.3 (31%); WB2, 76.9 (16%); WB3, 87.6 (25%)]. At weeks 24 and 48, 90% and 92% of participants had plasma HIV RNA <200 copies/mL. CONCLUSIONS: Generic DTG-DT provided adequate drug exposure in children weighing 6 to <20 kg. The exploratory dose of DTG 20 mg for children weighing 6 to <10 kg showed similar PK parameters to World Health Organization doses in the other WB.

Social Network Strategy to Promote HIV Testing and Linkage to HIV Services among Young men who Have sex with men and Transgender Women in Thailand.

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.

A Mobile Phone App to Support Adherence to Daily HIV Pre-exposure Prophylaxis Engagement Among Young Men Who Have Sex With Men and Transgender Women Aged 15 to 19 Years in Thailand: Pilot Randomized Controlled Trial.

BACKGROUND: Widespread smartphone use provides opportunities for mobile health HIV prevention strategies among at-risk populations. OBJECTIVE: This 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. METHODS: A 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. RESULTS: Between 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<10) and the YFS arm, although this did not reach statistical significance. Of the 100 participants in the YFS+APP arm, 23 (23%) were interviewed. The risk assessment function is perceived as the most useful app feature. Further aesthetic adaptations and a more comprehensive rewards system were suggested by the interviewees. CONCLUSIONS: Higher rates of PrEP adherence among frequent app users were observed; however, this was not statistically significant. A short app use duration of 3 months suggests that they may be useful in establishing habits in taking daily PrEP, but not long-term adherence. Further studies on the specific mechanisms of mobile phone apps that influence health behaviors are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT03778892; https://clinicaltrials.gov/ct2/show/NCT03778892.

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.

Integration of mental health services into HIV healthcare facilities among Thai adolescents and young adults living with HIV.

INTRODUCTION: To assess the burden of depression, anxiety and suicidality; and to determine the impact of integrated mental health and HIV services on treatment outcomes among Thai adolescents and young adults living with HIV (AYHIV). METHODS: A multicentre prospective cohort study was conducted among AYHIV (15 to 25 years), and age- and sex-matched HIV-uninfected adolescents and young adults (HUAY). The Patient Health Questionnaire 9-item (PHQ-9) and Generalized Anxiety Disorder 7-item scales (GAD-7) were used as screening tools for depressive and anxiety symptoms respectively. History of lifetime and recent suicidal ideations/attempts were ascertained. Elevated mental health screening scores were defined as having either significant depressive symptoms (PHQ-9 ≥9), significant anxiety symptoms (GAD-7 ≥10) or suicidality (lifetime; and recent [within two weeks]). Participants meeting these criteria were referred to psychiatrists for confirmatory diagnosis and mental health services. Follow-up assessment with PHQ-9 and GAD-7 was performed one year after psychiatric referral. RESULTS: From February to April 2018, 150 AYHIV and 150 HUAY were enrolled, median age was 19.0 (IQR:16.8 to 21.8) years and 56% lived in urban areas. Among AYHIV, 73% had HIV RNA <50 copies/mL, and median CD4 count was 580 (IQR:376 to 744) cells/mm3 . At enrolment, 31 AYHIV (21%; 95%CI:14% to 28%) had elevated mental health screening scores; 17 (11%) significant depressive symptoms, 11 (7%) significant anxiety symptoms and 21 (14%) suicidality. Seven AYHIV (5%) had all three co-existing conditions. These prevalences were not substantially different from HUAY. Urban living increased risk, whereas older age decreased risk of elevated mental health screening scores (p < 0.05). All AYHIV with elevated mental health screening scores were referred to study psychiatrists, and 19 (13%; 95%CI: 8% to 19%) had psychiatrist-confirmed mental health disorders (MHDs), including adjustment disorder (n = 5), major depression (n = 4), anxiety disorders (n = 2), post-traumatic stress disorder (n = 1) and mixed MHDs (n = 4). One year after psychiatric referral, 42% of AYHIV who received mental health services demonstrated an absence of significant mental health symptoms from the reassessments, and 26% had an improved score. CONCLUSIONS: With the significant burden of MHDs among AYHIV, an integration of mental health services, including mental health screenings, and psychiatric consultation and referral, is critically needed and should be scaled up in HIV healthcare facilities.

Youth-friendly services and a mobile phone application to promote adherence to pre-exposure prophylaxis among adolescent men who have sex with men and transgender women at-risk for HIV in Thailand: a randomized control trial.

INTRODUCTION: Strategies are needed to curb the increasing HIV incidence in young men who have sex with men (YMSM) and transgender women (YTGW) worldwide. We assessed the impact of youth-friendly services (YFS) and a mobile phone application (app) on adherence to pre-exposure prophylaxis (PrEP) in YMSM and YTGW in Thailand. METHODS: A randomized control trial was conducted in YMSM and YTGW aged 15 to 19 years. Participants were provided daily oral tenofovir disoproxil fumerate/emtricitabine (TDF/FTC), condoms and randomized to receive either YFS or YFS plus a PrEP app (YFS + APP), whose features included self-assessment of HIV acquisition risk, point rewards and reminders for PrEP and clinic appointments. Clinic visits occurred at zero, one, three and six months and telephone contact at two, four and five months. HIV testing was performed at every clinic visit. PrEP adherence was evaluated with intracellular tenofovir diphosphate (TFV-DP) concentrations in dried blood spot (DBS) samples at months 3 and 6. The primary endpoint assessed was "PrEP adherence" defined as TFV-DP DBS concentrations ≥700 fmol/punch (equivalent to ≥4 doses of TDF/week). RESULTS: Between March 2018 and June 2019, 489 adolescents were screened at three centres in Bangkok. Twenty-seven (6%) adolescents tested positive for HIV and 200 (41%) adolescents participated in the study. Of these, 147 were YMSM (74%) and 53 YTGW (26%). At baseline, median age was 18 years (IQR 17 to 19), 66% reported inconsistent condom use in the past month. Sexually transmitted infection prevalence was 23%. Retention at six months was 73%. In the YFS + APP arm, median app use duration was three months (IQR 1 to 5). PrEP adherence at month 3 was 51% in YFS and 54% in YFS + APP (p-value 0.64) and at month 6 was 44% in YFS and 49% in YFS + APP (p-value 0.54). No HIV seroconversions occurred during 75 person years of follow-up. CONCLUSIONS: Youth-friendly PrEP services enabled good adherence among half of adolescent PrEP users. However, the mobile phone application tested did not provide additional PrEP adherence benefit in this randomized trial. Adolescent risk behaviours are dynamic and require adaptive programmes that focus on "prevention-effective adherence."

CHAMP+ Thailand: Pilot Randomized Control Trial of a Family-Based Psychosocial Intervention for Perinatally HIV-Infected Early Adolescents.

Within Asia, HIV prevalence is highest in Thailand, including thousands of children and adolescents. Care for children born with HIV [perinatal transmission of HIV (PHIV)] will need to focus on adolescents for the foreseeable future. Thai PHIV adolescents experience significant mental health and psychosocial challenges, including treatment adherence. Yet, few, if any, comprehensive interventions for them exist. CHAMP+, an evidence-based intervention adapted for Thailand, was evaluated with a pilot randomized control trial at four HIV clinics. Eighty-eight dyads of 9- to 14-year-old PHIV young adolescents/caregivers were randomized to CHAMP+ or standard of care (SOC). Eleven cartoon-based sessions were delivered over 6 months. Participants completed baseline, 6-month (postintervention), and 9-month surveys, measuring youth outcomes (e.g., mental health and adherence), contextual factors (e.g., demographics and caregiver factors), and self- and social-regulation factors (e.g., HIV knowledge and youth-caregiver communication). Multi-level modeling to account for clustering within individuals was used to assess longitudinal changes within and between groups. All families randomized to CHAMP+ completed the intervention. Although the study was not statistically powered to detect differences in treatment effects, the CHAMP+ group significantly improved at 6 months in youth mental health and adherence, HIV knowledge, youth-caregiver communication, internalized stigma, and HIV-related social support, with most improvements sustained at 9 months and significantly better improvements than the SOC group on a number of outcomes. High levels of baseline viral suppression highlight the importance of reaching these young PHIV adolescents at a period of lower risk before adherence and other challenges emerge. Designed to be delivered with limited cost/resources, CHAMP+ Thailand holds scale-up potential.

A Qualitative Exploration of Psychosocial Challenges of Perinatally HIV-Infected Adolescents and Families in Bangkok, Thailand.

Thailand has the highest HIV prevalence in Asia, with 9,600 HIV+ adolescents and thousands additional younger HIV+ children (World Bank, 2015; UNICEF, 2015). Studies from other settings suggest perinatally HIV-infected (PHIV+) adolescents are at high risk for mental health problems and engagement in risk behaviors that threaten individual and public health. Yet, few studies exist in Thailand, and few evidence-based psychosocial interventions have been developed for and studied in this population, despite great need. The current study qualitatively explored psychosocial issues among Thai PHIV+ adolescents to inform development or adaptation of interventions. Thai and US-based researchers and clinicians conducted two focus group discussions with PHIV+ adolescents aged 12-16 and their adult caregivers, and six in-depth key informant interviews with health/social work providers at a large clinic for PHIV+ youth in Bangkok, Thailand. Data were analyzed thematically using framework analysis. Multiple challenges for PHIV+ youth and caregivers were identified. Adherence to antiretroviral treatment was a significant challenge attributed to lack of adult support, side effects, feeling too well to take medicines, and avoiding acknowledging sickness. Poor child-caregiver communication and conflict was a key concern, explained in part by cultural expectation of obedience and generation gaps. Concerns about societal stigma and discrimination emerged strongly and influenced delay or avoidance of disclosing HIV status to children and others. Respondents identified positive approaches to addressing these issues and highlighted the need for interventions to improve child-caregiver communication and generate peer and community support for PHIV+ youth. Thai PHIV+ adolescents and families experience significant psychosocial challenges, similar to those seen in other contexts. Cultural adaptation of an existing evidence-based clinic-based family group intervention is recommended to rapidly address these needs.

Cultural Adaptation of an Evidence-Informed Psychosocial Intervention to Address the Needs of PHIV+ Youth in Thailand.

Globally, pediatric HIV has largely become an adolescent epidemic. Thailand has the highest HIV prevalence in Asia (1.2%), with more than 14,000 children living with HIV. There is growing demand for evidence-based psychosocial interventions for this population that include health and mental health support and sexual risk reduction, which can be integrated into HIV care systems. To address this need, a multidisciplinary team of Thai and US researchers adapted an existing evidence-informed, family-based intervention, The Collaborative HIV Prevention and Adolescent Mental Health Program + (CHAMP+), which has been tested in multiple global trials. Using community-based participatory research methods, changes to the intervention curriculum were made to address language, culture, and Thai family life. Involvement of families, youth, and stakeholders in the adaptation process allowed for identification of salient issues and of program delivery methods that would increase engagement. Participants endorsed using a cartoon-based curriculum format for fostering discussion (as in CHAMP+ South Africa) given stigma around discussing HIV in the Thai context. The Thai version of CHAMP+ retained much of the curriculum content incorporating culturally appropriate metaphors and story line. Sessions focus on family communication, coping, disclosure, stigma, social support, and HIV education. This paper explores lessons learned through the adaption process of CHAMP+ Thailand that are applicable to other interventions and settings. It discusses how culturally informed adaptations can be made to interventions while maintaining core program components.