Publications by authors named "Torsak Bunupuradah"

97 Publications

Impact of low-level viraemia on virological failure among Asian children with perinatally acquired HIV on first-line combination antiretroviral treatment: a multicentre, retrospective cohort study.

J Int AIDS Soc 2020 07;23(7):e25550

Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.

Introduction: The clinical relevance of low-level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first-line combination antiretroviral therapy (cART).

Methods: CLHIV aged <18 years, who were on first-line cART for ≥12 months, and had virological suppression (two consecutive plasma viral load [pVL] <50 copies/mL) were included. Those who started treatment with mono/dual antiretroviral therapy, had a history of treatment interruption >14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF.

Results: From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non-nucleoside reverse transcriptase inhibitor-based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow-up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person-years of follow-up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU; p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60).

Conclusions: LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first-line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF.
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http://dx.doi.org/10.1002/jia2.25550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338042PMC
July 2020

Nonalcoholic fatty liver disease and hepatic fibrosis among perinatally HIV-monoinfected Asian adolescents receiving antiretroviral therapy.

PLoS One 2019 19;14(12):e0226375. Epub 2019 Dec 19.

HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10-25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ≥7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6-19.2) years and 10.5 (7.1-12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8-18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (≥2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7-511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1-289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226375PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922447PMC
March 2020

A survey of management practices in coexistent allergic rhinitis and asthma (Asia-pacific Survey of Physicians on Asthma and allergic Rhinitis): results from Thailand.

Asia Pac Allergy 2019 Jul 9;9(3):e24. Epub 2019 Jul 9.

GlaxoSmithKline Limited, Singapore.

Background: Underdiagnosis and undertreatment of allergic rhinitis (AR) in patients with asthma can worsen treatment outcomes. There is limited evidence of clinical practices for management of coexistent AR-asthma in Thailand.

Methods: A multicountry, cross-sectional study (Asia-pacific Survey of Physicians on Asthma and allergic Rhinitis) to evaluate physician perceptions and management practices related to AR-asthma overlap in 6 Asian countries was conducted. For Thailand specifically, AR-asthma linkage questionnaires were developed and translated to Thailaland. General physicians (GPs) or pediatricians, randomly selected from hospitals in urban cities, routinely treating >10 asthma patients/month were interviewed. Here we present the results for Thailand.

Results: Two hundred physicians (100 GPs and 100 pediatricians), of whom 70% worked in government hospitals, were interviewed. In their experience, 50% of asthma patients had AR and 28% of AR patients had asthma. Among diagnosed asthma patients, 65% of physicians routinely asked for any AR symptoms at every visit. Among diagnosed AR patients, 63% of physicians routinely asked for any asthma symptoms at every visit. In patients with coexisting AR-asthma, 91% of physicians treated both diseases simultaneously, while 6% of physicians treated asthma as a chronic disease but managed AR symptomatically. The most preferred treatment options for patients with AR-asthma were inhaled corticosteroids with intranasal steroids (46% in GPs, 71% in pediatricians).

Conclusion: The physicians interviewed in Thailand are aware about coexistent asthma-AR. There is a need to increase the awareness further for coexistent AR-asthma and to educate nonspecialist physicians in the proper management of AR-asthma patients.
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http://dx.doi.org/10.5415/apallergy.2019.9.e24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676060PMC
July 2019

Impact of the frequency of plasma viral load monitoring on treatment outcomes among children with perinatally acquired HIV.

J Int AIDS Soc 2019 06;22(6):e25312

Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.

Introduction: Recommendations on the optimal frequency of plasma viral load (pVL) monitoring in children living with HIV (CLWH) who are stable on combination antiretroviral therapy (cART) are inconsistent. This study aimed to determine the impact of annual versus semi-annual pVL monitoring on treatment outcomes in Asian CLWH.

Methods: Data on children with perinatally acquired HIV aged <18 years on first-line, non-nucleoside reverse transcriptase inhibitor-based cART with viral suppression (two consecutive pVL <400 copies/mL over a six-month period) were included from a regional cohort study; those exposed to prior mono- or dual antiretroviral treatment were excluded. Frequency of pVL monitoring was determined at the site-level based on the median rate of pVL measurement: annual 0.75 to 1.5, and semi-annual >1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000 copies/mL), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL <400 copies/mL. Competing risk regression models were used to identify predictors of treatment failure.

Results: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi-annual pVL monitoring (n = 4) respectively. Pre-cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 log copies/mL. At baseline, the median age was 9.2 years, 64% were on nevirapine-based regimens, the median cART duration was 1.6 years, and the median CD4 percentage was 26%. Over the follow-up period, 258 (25%) CLWH with annual and 40 (23%) with semi-annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient-years of follow-up respectively (p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59).

Conclusions: Annual compared to semi-annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first-line NNRTI-based cART.
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http://dx.doi.org/10.1002/jia2.25312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556679PMC
June 2019

Validation of a self-report adherence measurement tool among a multinational cohort of children living with HIV in Kenya, South Africa and Thailand.

J Int AIDS Soc 2019 05;22(5):e25304

Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya.

Introduction: There are few data on adherence and low-cost measurement tools for children living with HIV. We collected prospective data on adherence to antiretroviral therapy (ART) among a multinational cohort of children to evaluate an adherence questionnaire.

Methods: We enrolled 319 children ages 0 to 16 years on ART in Kenya (n = 110), South Africa (n = 109) or Thailand (n = 100). Children were followed up for six months of adherence monitoring between March 2015 and August 2016 using Medication Event Monitoring Systems (MEMS ) with at least one viral load measure. At month 3 and 6, children or their caregivers were administered a 10-item adherence questionnaire. Repeated measures analyses were used to compare responses on questionnaire items to external adherence criteria: MEMS dichotomized adherence (≥90% of doses taken vs. <90%), 48-hour MEMS treatment interruptions and viral suppression (<1000 copies/mL). Items associated with outcomes (p < 0.10) were coefficient-weighted to calculate a total adherence score, which was tested in multivariate regression against MEMS and viral suppression outcomes. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated.

Results: Mean child age was 11 years and 54% were female. Children from Thailand (median age 14 years) were significantly older compared to Kenya (10 years) and South Africa (10 years). Prevalence of viral suppression was 97% in Thailand, 81% in South Africa and 69% in Kenya, while the prevalence of MEMS adherence ≥90% was 57% in Thailand, 58% in South Africa and 40% in Kenya. Across sites, child-reported adherence using the questionnaire was significantly associated with dichotomized MEMS adherence (OR 1.8, 95% CI 1.4 to 2.4), 48-hour treatment interruptions (OR 0.41, 95% CI 0.3 to 0.6), and viral suppression (OR 3.4, 95% CI 1.7 to 6.7). We did find, however, that different cut-points for the adherence score may be context-specific. For example, MEMS non-adherent children in Kenya had a lower adherence score (0.98) compared to South Africa (1.77) or Thailand (1.58).

Conclusions: We found suboptimal adherence to ART was common by multiple measures in this multi-country cohort of children. The short-form questionnaire demonstrated reasonable validity to screen for non-adherence in these diverse settings.
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http://dx.doi.org/10.1002/jia2.25304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543456PMC
May 2019

Influence of and polymorphisms on atazanavir/r concentrations in Thai HIV-infected patients.

Pharmacogenomics 2019 05;20(7):517-527

Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.

To evaluate the influence of genetic polymorphisms on plasma trough concentrations of atazanavir (ATV) and ritonavir (RTV). The concentration-to-dose ratios were compared between different genotype groups of , ,  and in 490 patients. Multiple regression analysis was used to examine the association between genetic and clinical factors and log-transformed concentration-to-dose ratio of ATV and RTV. Higher concentrations of ATV and RTV were significantly associated with 6986 GG and 521 TC or CC. Female patients had significantly higher ATV plasma concentration than male patients. Genetic polymorphisms and gender are factors affecting the variability of ATV and RTV concentrations in the Thai population. Thus, genetic testing is worth considering when atazanavir + low dose ritonavir is prescribed.
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http://dx.doi.org/10.2217/pgs-2018-0196DOI Listing
May 2019

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

AIDS Patient Care STDS 2019 05;33(5):227-236

1 HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute and Columbia University, New York, New York.

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.
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http://dx.doi.org/10.1089/apc.2019.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531900PMC
May 2019

Early and Late Virologic Failure After Virologic Suppression in HIV-Infected Asian Children and Adolescents.

J Acquir Immune Defic Syndr 2019 03;80(3):308-315

Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Background: Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving.

Setting: An Asian cohort in 16 pediatric HIV services across 6 countries.

Methods: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA ≥1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA ≥1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure.

Results: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure.

Conclusions: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required.
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http://dx.doi.org/10.1097/QAI.0000000000001921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952284PMC
March 2019

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

Vulnerable Child Youth Stud 2018 21;13(2):158-169. Epub 2017 Jul 21.

HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute and Columbia University, 1051 Riverside Drive, Unit 15, New York, NY 10032, United States.

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.
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http://dx.doi.org/10.1080/17450128.2017.1356947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190906PMC
July 2017

Seroprevalence of Hepatitis B Among HIV-infected Children and Adolescents Receiving Antiretroviral Therapy in the TREAT Asia Pediatric HIV Observational Database.

Pediatr Infect Dis J 2018 08;37(8):788-793

Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Background: Hepatitis B (HBV)-HIV coinfection is associated with liver inflammation, which can progress to liver fibrosis/cirrhosis and hepatocellular carcinoma. We determined HBV seroprevalence in children and adolescents participating in the TREAT Asia Pediatric HIV Observational Database.

Methods: A multisite cross-sectional study was conducted in HIV-infected patients currently <25 years old receiving antiretroviral treatment (ART) who had HBV surface antigen (HBsAg), or HBV surface antibody (anti-HBs) or HBV core antibody (anti-HBc) tested during 2012-2013. HBV coinfection was defined as having either a positive HBsAg test or being anti-HBc positive and anti-HBs negative, reflective of past HBV infection. HBV seroprotection was defined as having a positive anti-HBs test.

Results: A total of 3380 patients from 6 countries (Vietnam, Thailand, Cambodia, Malaysia, Indonesia and India) were included. The current median (interquartile range) age was 11.2 (7.8-15.1) years. Of the 2755 patients (81.5%) with HBsAg testing, 130 (4.7%) were positive. Of 1558 (46%) with anti-HBc testing, 77 (4.9%) were positive. Thirteen of 1037 patients with all 3 tests were anti-HBc positive and HBsAg and anti-HBs negative. One child was positive for anti-HBc and negative for anti-HBs but did not have HBsAg tested. The prevalence of HBV coinfection was 144/2759 (5.2%) (95% confidence interval: 4.4-6.1). Of 1093 patients (32%) with anti-HBs testing, 257 (23.5%; confidence interval: 21.0-26.0) had positive tests representing HBV seroprotection.

Conclusions: The estimated prevalence of HBV coinfection in this cohort of Asian HIV-infected children and adolescents on ART was 5.2%. The majority of children and adolescents tested in this cohort (76.5%) did not have protective HBV antibody. The finding supports HBV screening of HIV-infected children and adolescents to guide revaccination, the use of ART with anti-HBV activity and future monitoring.
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http://dx.doi.org/10.1097/INF.0000000000001901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097529PMC
August 2018

Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial.

PLoS One 2018 23;13(4):e0196239. Epub 2018 Apr 23.

MRC CTU, University College London Institute of Clinical Trials and Methodology, London, United Kingdom.

Background: Weekends off antiretroviral therapy (ART) may help engage HIV-1-infected young people facing lifelong treatment. BREATHER showed short cycle therapy (SCT; 5 days on, 2 days off ART) was non-inferior to continuous therapy (CT) over 48 weeks. Planned follow-up was extended to 144 weeks, maintaining original randomisation.

Methods: BREATHER was an open-label, non-inferiority trial. Participants aged 8-24yrs with virological suppression on efavirenz-based first-line ART were randomised 1:1, stratified by age and African/non-African sites, to remain on CT or change to SCT. The Kaplan-Meier method was used to estimate the proportion of participants with viral rebound (confirmed VL≥50 copies/mL) under intent-to-treat at 48 weeks (primary outcome), and in extended follow-up at 96, 144, and 192 weeks. SCT participants returned to CT following viral rebound, 3 VL blips or discontinuation of efavirenz.

Findings: Of 199 participants (99 SCT, 100 CT), 97 per arm consented to extended follow-up. Median follow-up was 185.3 weeks (IQR 160.9-216.1). 69 (70%) SCT participants remained on SCT at last follow-up. 105 (53%) were male, baseline median age 14 years (IQR 12-18), median CD4 count 735 cells/μL (IQR 576-968). 16 SCT and 16 CT participants had confirmed VL≥50 copies/mL by the end of extended follow-up (HR 1.00, 95% CI 0.50-2.00). Estimated difference in percentage with viral rebound (SCT minus CT) by week 144 was 1.9% (90% CI -6.6-10.4; p = 0.72) and was similar in a per-protocol analysis. There were no significant differences between arms in proportions of participants with grade 3/4 adverse events (18 SCT vs 16 CT participants; p = 0.71) or ART-related adverse events (10 vs 12; p = 0.82). 20 versus 8 serious adverse events (SAEs) were reported in 16 SCT versus 4 CT participants, respectively (p = 0.005 comparing proportions between groups; incidence rate ratio 2.49, 95%CI 0.71-8.66, p = 0.15). 75% of SAEs (15 SCT, 6 CT) were hospitalisations for a wide range of conditions. 3 SCT and 6 CT participants switched to second-line ART following viral failure (p = 0.50).

Conclusions: Sustainable non-inferiority of virological suppression in young people was shown for SCT versus CT over median 3.6 years. Standard-dose efavirenz-based SCT is a viable option for virologically suppressed HIV-1 infected young people on first-line ART with 3-monthly VL monitoring.

Trial Registration: EudraCT 2009-012947-40 ISRCTN 97755073 ClinicalTrials.gov NCT01641016.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196239PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912750PMC
July 2018

Effect of calcium and vitamin D supplementation on bone mineral accrual among HIV-infected Thai adolescents with low bone mineral density.

J Virus Erad 2018 Jan 1;4(1):6-11. Epub 2018 Jan 1.

Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

 The benefits of calcium and vitamin D supplementation for low bone mass remains controversial. This study assessed the changes in bone mineral density (BMD) during periods without and with calcium and vitamin D supplementation among HIV-infected adolescents with low BMD.  Perinatally HIV-infected Thai adolescents aged 12-20 years were enrolled into Phase 1 (pre-supplementation) to evaluate longitudinal change of BMD. We provided education about appropriate dietary intake and exercise. Lumbar spine (L2-L4) BMD and vitamin D status (25-hydroxyvitamin D [25(OH)D]) were assessed at baseline and at 12-24 month intervals. Participants with a BMD Z-score≤-2 were enrolled into Phase 2 (supplementation) that provided calcium 600 mg plus cholecalciferol 200 IU twice daily for 6 months. BMD and 25(OH)D were re-assessed at the end of study.  Ninety-four participants were enrolled into the Phase 1. Median age (IQR) was 14.3 (13.0-15.5) years, with 67% at Tanner stage 3-5, 89% with a plasma HIV-1 RNA<50 copies/mL. During Phase 1 and a 22.7-month follow-up, median L2-L4 BMD Z-scores remained unchanged (-1.06 -1.08, =0.08), but 25(OH)D levels increased (24.7 26.7 ng/mL, =0.01). Twenty-six (28%) adolescents had low BMD and were enrolled into Phase 2, with 24 (92%) completing follow-up. The median L2-L4 BMD Z-scores (-2.59 -1.70; <0.001) and calcium level (9.3 9.5 mg/dL, =0.04) significantly improved. There was an increase in BMD Z-scores during the 6-months post-supplementation as compared to the 21-month pre-supplementation period (0.65 -0.50, =0.03).  HIV-infected adolescents with low BMD had improved bone health after calcium and vitamin D supplementation. A randomised controlled trial is warranted to confirm the benefits of these supplements.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851189PMC
January 2018

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

Glob Soc Welf 2017 24;4(4):209-218. Epub 2017 Jul 24.

McSilver Institute for Poverty Policy and Research, New York University Silver School of Social Work, 41 East 11th Street, 7th Floor, New York, NY 10003 USA.

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.
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http://dx.doi.org/10.1007/s40609-017-0100-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660129PMC
July 2017

Pharmacokinetics of rilpivirine and 24-week outcomes after switching from efavirenz in virologically suppressed HIV-1-infected adolescents.

Antivir Ther 2018 ;23(3):259-265

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favourable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the pharmacokinetics (PK), safety and efficacy of RPV in virologically suppressed HIV-1-infected adolescents after switching from EFV.

Methods: Adolescents aged 12-18 years on EFV-based antiretroviral therapy (ART) were switched from EFV to RPV (25 mg, once daily). Intensive 24-h blood samplings at 0 (pre-dose), 1, 2, 4, 5, 6, 9, 12 and 24 h were performed 4 weeks after switching. PK parameters were calculated using a non-compartmental method and compared with published data from the PAINT and pooled ECHO/THRIVE substudies. HIV RNA level was measured at weeks 12 and 24. Biochemical profiles were measured at baseline and week 24.

Results: From January to June 2016, 20 adolescents (12 male) were enrolled. Median (IQR) age was 16 (15-17) years and weight was 49 (42-59) kg. Mean (sd) AUC, C and C of RPV were 2,041 (745) ng•h/ml, 69 (29) ng/ml and 143 (65) ng/ml, respectively. Median (IQR) T was 5 (2-9) h. Four adolescents had C <40 ng/ml. All PK parameters were comparable with published data. All adolescents remained virologically suppressed at week 24. Significant decreases in fasting total cholesterol, triglyceride and low-density lipoprotein were observed (P-value <0.05).

Conclusions: Virologically suppressed HIV-infected adolescents had adequate RPV exposure and remained virologically suppressed after switching from EFV. RPV can be used as long-term maintenance ART in HIV-infected adolescents.
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http://dx.doi.org/10.3851/IMP3198DOI Listing
September 2019

Multicentre analysis of second-line antiretroviral treatment in HIV-infected children: adolescents at high risk of failure.

J Int AIDS Soc 2017 09;20(1):21930

Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.

Introduction: The number of HIV-infected children and adolescents requiring second-line antiretroviral treatment (ART) is increasing in low- and middle-income countries (LMIC). However, the effectiveness of paediatric second-line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second-line ART outcomes for children and assessed the need for paediatric third-line ART.

Methods: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second-line ART in LMIC, contacting the corresponding study groups and including patient-level data on virologic and clinical outcomes. Kaplan-Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second-line treatment.

Results: We included 12 cohorts representing 928 children on second-line protease inhibitor (PI)-based ART in 14 countries in Asia and sub-Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9-19.4) of children experienced virologic failure. Adolescents (10-18 years) had failure rates of 14.5 (95% CI 11.9-17.6) per 100 person-years compared to 4.5 (95% CI 3.4-5.8) for younger children (3-9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93,  < 0.001) and short duration of first-line ART before treatment switch (aHR 0.64 and 0.53,  = 0.008, for 24-48 months and >48 months, respectively, compared to <24 months).

Conclusions: In LMIC, paediatric PI-based second-line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI-based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.
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http://dx.doi.org/10.7448/IAS.20.1.21930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640308PMC
September 2017

Strategies to improve the uptake of effective contraception in perinatally HIV-infected adolescents.

J Virus Erad 2017 Jul 1;3(3):152-156. Epub 2017 Jul 1.

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand.

Objective: To assess strategies to improve safe-sex practices in sexually active female adolescents living with HIV, through linking reproductive health (RH) care with HIV care.

Methods: A single arm, 48-week prospective study was conducted with 77 sexually active adolescents in five sites in Thailand. Guided RH education was carried out through video, brochures and individual counselling. Participants were offered free effective contraception (EC), in addition to a barrier method (dual contraception) versus barrier method only. Changes in EC use were assessed with McNemar's test; predicting factors with logistic regression.

Results: Median age was 19 years; 95% were perinatally infected; 30% had been pregnant. All but one showed RH-knowledge improvement after RH education. Individual counselling was most often rated the 'most helpful' educational method. At the screening visit 21% were using dual contraception; 53% a male condom only; 8% EC method only; and 18% were not using any contraceptive method. Dual-contraception use improved with time, reaching 74% at week 48. EC-use at the baseline visit was associated with having ever used EC prior to study entry (<0.0001), and the study site (<0.0001). Having ever used EC was associated with a history of pregnancy (=0.0085) and forced sex (=0.0386).

Conclusion: Offering continuous RH care, linked with HIV care, resulted in increased use of dual contraception. Healthcare providers played a significant role in the process. RH education should address the main predictors for EC use by adolescents, including past, personal experience.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518244PMC
July 2017

Prevalence of Persistent Renal Dysfunction in Perinatally HIV-infected Thai Adolescents.

Pediatr Infect Dis J 2018 Jan;37(1):66-70

From the The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre, Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Excellence center in Pediatric Infectious Diseases and Vaccines, Chulalongkorn University, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, and Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: Persistent renal dysfunction (PRD) has been reported in up to 22% of perinatally HIV-infected adolescents (PHAs) in the United States and Europe. There are limited data available on PRD among PHAs in resource-limited settings regarding access to antiretroviral therapy (ART) at more advanced HIV stages.

Methods: We retrospectively described the prevalence of PRD and associated factors in a Thai PHA cohort. Inclusion criteria were current age ≥10 years old and at least 2 serum creatinine (Cr) measurements after ART initiation. Cr and urine examination were performed every 6-12 months. PRD was defined as having ≥2 measurements of low estimated glomerular filtration rate (eGFR); either <60 mL/min/1.73 m2 or elevated Cr for age and eGFR 60-89 mL/min/1.73 m2, or proteinuria (dipstick proteinuria ≥1+). Factors associated with PRD were analyzed using a multivariate logistic regression analysis.

Results: This study included 255 PHAs with median (interquartile range) age of 16.7 (14.5-18.8) and ART duration of 10.3 (7.1-12.4) years. Fifty-six percentage used boosted protease inhibitor (bPI)-based regimens, and 63% used tenofovir disoproxil fumarate (TDF). The overall PRD prevalence was 14.1% [95% confidence interval (CI): 10.1-19.0]; low eGFR 6.7%, proteinuria 3.5% and both 3.9%. Among 109 users of TDF with bPI, 22.9% had PRD and 2.8% discontinued/adjusted dosing of TDF because of nephrotoxicity. Factors associated with PRD were age 10-15 years old (adjusted odd ratio (aOR): 10.1, 95% CI: 4.1-25.2), male (aOR: 3.2, 95% CI: 1.4-7.7), CD4 nadir <150 cells/mm (aOR: 2.6, 95% CI: 1.1-6.1) and use of TDF with bPI (aOR: 9.6, 95% CI: 3.2-28.9).

Conclusions: PRD is common among PHAs. Almost one-fifth of adolescents using TDF with bPI had PRD. These adolescents should be a priority group for renal monitoring.
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http://dx.doi.org/10.1097/INF.0000000000001684DOI Listing
January 2018

Attrition and Mortality of Children Receiving Antiretroviral Treatment through the Universal Coverage Health Program in Thailand.

J Pediatr 2017 09 9;188:210-216.e1. Epub 2017 Jun 9.

Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Objective: To assess mortality and loss to follow-up of children with HIV infection who started antiretroviral therapy (ART) through the Universal Coverage Health Program (UC) in Thailand.

Study Design: Children with HIV infection who initiated ART at age <15 years through the UC between 2008 and 2013 were included in the analysis. Death was ascertained through linkage with the National Death Registry. A competing-risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for loss to follow-up. Death was considered a competing risk. Cox proportional hazards models were used to assess predictors of mortality.

Results: A total of 4618 children from 497 hospitals in Thailand were included in the study. Median age at ART initiation was 9 years (IQR, 6-12 years), and the median duration of tracking was 4.1 years (a total of 18 817 person-years). Three hundred and ninety-five children (9%) died, for a mortality rate of 2.1 (95% CI, 1.9-2.3) per 100 person-years, and 525 children (11%) were lost to follow-up, for a lost to follow-up rate of 2.9 (95% CI, 2.7-3.2) per 100 person-years. The cumulative incidence of loss to follow-up increased from 4% at 1 year to 8.8% at 3 years. Children who started ART at age ≥12 years were at the greatest risk of loss to follow-up. The probability of death was 3.2% at 6 months and 6.4% at 3 years. Age ≥12 years at ART initiation, lower baseline CD4%, advanced HIV staging, and loss to follow-up were associated with mortality.

Conclusion: The Thai national HIV treatment program has been very effective in treating children with HIV infection, with low mortality and modest rates of loss to follow-up.
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http://dx.doi.org/10.1016/j.jpeds.2017.05.035DOI Listing
September 2017

Brief Report: Pediatric Cancer Burden and Treatment Resources Within the Pediatric IeDEA Consortium.

J Acquir Immune Defic Syndr 2017 09;76(1):60-64

*Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN; †Division of Infectious Diseases, Virginia Commonwealth University, Richmond, VA; ‡Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; §HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‖TREAT Asia/amfAR, The Foundation for AIDS Research, Bangkok, Thailand; ¶Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa; #KorleBu Hospital, Accra, Ghana; **Inserm U1027, University Toulouse 3, Toulouse, France; ††Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC; ‡‡Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, OH; §§Vanderbilt University School of Medicine, Nashville, TN; ‖‖Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC; and ¶¶Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.

Introduction: The incidence and treatment of cancer in HIV-infected children from resource-limited settings has not been extensively studied.

Objectives: Develop and implement a cross-sectional survey to evaluate pediatric cancer burden, diagnostic modalities in use, and treatment availability as perceived by HIV clinic staff at regional International Epidemiology Databases to Evaluate AIDS (IeDEA) sites.

Methods: IeDEA regional investigators developed a cross-sectional clinical site survey which included questions on the numbers and types of pediatric cancers observed, modalities used to treat identified cancers, and treatment options available at individual sites in the Asia-Pacific, Latin America, Central Africa, East Africa, West Africa, and Southern Africa regions.

Results: Kaposi sarcoma, non-Hodgkin lymphoma, and Burkitt lymphoma were reported by site personnel to be the most prevalent types of cancer in the pediatric HIV population. Survey results indicate that access to comprehensive cancer treatment modalities is very limited for children in these regions despite HIV care and treatment sites reporting that they diagnose pediatric cancers. Responses also showed that evaluating cancer in the pediatric HIV population is a challenge due to a lack of resources and varying treatment availability within regions.

Conclusions: Further study is needed to increase our understanding of the changing epidemiology of cancer in HIV-infected pediatric populations. Increased financial and technical resources are critical to aid in the advancement of health services to support treatment of these children in resource-constrained settings.
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http://dx.doi.org/10.1097/QAI.0000000000001453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552429PMC
September 2017

First-Line Antiretroviral Treatment Outcomes and Durability in HIV-Infected Children Treated Through the Universal Coverage Health Program in Thailand.

J Acquir Immune Defic Syndr 2017 06;75(2):219-225

*HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; †Kirby Institute, University of New South Wales, Sydney, Australia; ‡Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; §Research Unit in Pediatric Infectious Diseases and Vaccines, Chulalongkorn University, Bangkok, Thailand; ‖Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute of Global Health and Development, Amsterdam, the Netherlands; ¶Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; #The HIV/AIDS, Tuberculosis and Infectious Diseases Program, National Health Security Office (NHSO), Bangkok, Thailand; and **Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: We assessed the treatment outcomes on first-line antiretroviral therapy (ART), and factors associated with switching regimen in HIV-infected children treated through the universal coverage health program (UC) in Thailand.

Methods: Children aged <15 years at ART initiation who had been receiving ART for at least 6 months between 2008 and 2014 through UC were included in the analysis. The Kaplan-Meier method was used to estimate immunological recovery (IMR), immunological failure, and virological failure (VF). Cox models were used to assess predictors of IMR and VF. Competing risk models were used to assess factors associated with switching to a second-line regimen, with death considered as a competing risk.

Results: A total of 4120 children initiated ART at a median (interquartile range) age of 9.3 (5.8-12.0) years. The median duration of ART was 3.7 years with 17,950 person-years of follow-up. Two thousand eight hundred five children achieved IMR, and the probability of IMR increased to 76% by 3 years after ART initiation. Among 1054 children switched to second-line regimens, 84% had VF and 19% had immunological failure. The cumulative rate of switching regimen increased from 4% to 20% from 1 to 3 years after treatment. Children aged ≥12 years at ART initiation, starting with nonnucleoside reverse-transcriptase inhibitors, and baseline CD4% <10% had an increased risk of switching to second-line regimens.

Conclusions: Children receiving ART through UC had good treatment outcomes, although a fifth required switching regimen by 3 years. Earlier treatment initiation and avoiding nonnucleoside reverse-transcriptase inhibitor first-line regimens in high-risk children may prevent treatment failure.
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http://dx.doi.org/10.1097/QAI.0000000000001351DOI Listing
June 2017

Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy.

J Adolesc Health 2017 Jul 24;61(1):91-98. Epub 2017 Mar 24.

Faculty of Medicine, The Kirby Institute, UNSW Australia, Sydney, Australia.

Purpose: To assess the incidence and predictors of postsuppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy in Asia.

Methods: Perinatally HIV-infected Asian adolescents (10-19 years) with documented virologic suppression (two consecutive viral loads [VLs] <400 copies/mL ≥6 months apart) were included. Baseline was the date of the first VL <400 copies/mL at age ≥10 years or the 10th birthday for those with prior suppression. Cox proportional hazards models were used to identify predictors of postsuppression VR (VL >1,000 copies/mL).

Results: Of 1,379 eligible adolescents, 47% were males. At baseline, 22% were receiving protease inhibitor-containing regimens; median CD4 cell count (interquartile range [IQR]) was 685 (448-937) cells/mm; 2% had preadolescent virologic failure (VF) before subsequent suppression. During adolescence, 180 individuals (13%) experienced postsuppression VR at a rate of 3.4 (95% confidence interval: 2.9-3.9) per 100 person-years, which was consistent over time. Median time to VR during adolescence (IQR) was 3.3 (2.1-4.8) years. Wasting (weight-for-age z-score <-2.5), being raised by grandparents, receiving second-line protease inhibitor-based regimens, starting combination antiretroviral therapy after 2005, and having preadolescent VF were independent predictors of adolescent VR. At VR, median age, CD4 cell count, and VL (IQR) were 14.8 (13.2-16.4) years, 507 (325-723) cells/mm, and 4.1 (3.5-4.7) log copies/mL, respectively.

Conclusions: A modest and consistent incidence of postsuppression VR was documented during adolescence in our cohort. Having poor weight, receiving second-line regimens, and prior VF were associated with an increased VR rate. Adolescents at higher risk of VR may benefit from more intensive VL monitoring to enhance adherence management.
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http://dx.doi.org/10.1016/j.jadohealth.2017.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483211PMC
July 2017

Carbohydrate, lipid, bone and inflammatory markers in HIV-positive adolescents on antiretroviral therapy and hormonal contraception.

J Virus Erad 2017 Jan 1;3(1):56-60. Epub 2017 Jan 1.

HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand; SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Background: Little is known about the cumulative effect of HIV antiretroviral therapy (ART) and hormonal contraception (HC) on metabolism and inflammation in HIV-positive women.

Methods: We conducted a cross-sectional assessment of markers for carbohydrate, lipid, bone metabolism, inflammation and coagulation in HIV-positive adolescents on ART and HC (=37) versus on ART only (=51) in Thailand. The Wilcoxon rank-sum test was used to assess differences between groups.

Results: The median age was 19.5 years. Most adolescents (95%) were perinatally infected. All were on ART for a median of 9 years. HC used was progestin only (=21); combined oral contraceptive (COC) tablets (=6) for the whole study period or alternating between progestin only and COC (=10). Prevalence of any metabolic abnormalities was 99%. Four biomarkers were significantly higher with HC no HC: insulin (10.3 6.2 μU/mL, =0.002), insulin resistance (1.89 1.19 mass units, =0.005), 25-OH vitamin D (33.2 20.2 ng/mL, <0.0001) and C-terminal telopeptide (690 530 ng/L, =0.011). Triglycerides and D-dimer were significantly lower with HC (103 139 mg/dL, =0.014 and 140 155 ng/mL, =0.003, respectively). There was no relationship between the type of HC or ART and the above differences.

Conclusion: Perinatally infected HIV-positive adolescents on ART in this pilot study had a high prevalence of metabolic abnormalities. Bone turnover markers and insulin resistance were significantly higher with HC. Research on the cumulative effect of HIV, ART and HC on metabolism and inflammation in adolescents with HIV is important in order to devise strategies for preventing and mitigating long-term comorbidities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337422PMC
January 2017

HIV-infected children in the Asia-Pacific region with baseline severe anemia: antiretroviral therapy and outcomes.

Asian Biomed (Res Rev News) 2016 Jun;10(3):229-234

The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.

Background: Severe anemia is common among children infected with human immunodeficiency virus (HIV). The choice of antiretroviral (ART) regimen needs careful consideration. No information is available regarding the initial ART regimens used in the Asia-Pacific region and the rate of switch of ART regimens in HIV-infected children with severe anemia.

Objectives: To study the initial ART regimens and the rate of switch of ART regimens used during the first 36 months in HIV-infected children with severe anemia and to evaluate their clinical and laboratory outcomes.

Methods: We analyzed regional cohort data of 130 Asian children aged <18 years with baseline severe anemia (hemoglobin <7.5 g/dl) who started antiretroviral therapy (ART) between January 2003 and September 2013.

Results: At ART initiation, median age was 3.5 years old (interquartile range (IQR) 1.7 to 6.3) and median hemoglobin was 6.7 g/dL (IQR 5.9-7.1, range 3.0-7.4). Initial ART regimens included stavudine (85.4%), zidovudine (13.8%), and abacavir (0.8%). In 81 children with available hemoglobin data after 6 months of ART, 90% recovered from severe anemia with a median hemoglobin of 10.7 g/dL (IQR 9.6-11.7, range 4.4-13.5). Those starting AZT-based ART had a mortality rate of 10.8 (95% confidence interval (CI) 4.8-23.9) per 100 patient-years compared to 2.7 (95% CI 1.6-4.6) per 100 patient-years among those who started d4T-based ART.

Conclusions: With the phase-out of stavudine, age-appropriate non-zidovudine options are needed for younger Asian children with severe anemia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321077PMC
June 2016

Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses.

J Virol 2017 04 13;91(7). Epub 2017 Mar 13.

Centre de Recherche du CHUM, Montreal, QC, Canada

HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid the exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to the CD4-bound state. While residue S375 is well conserved in the majority of group M HIV-1 isolates, CRF01_AE strains have a naturally occurring histidine at this position (H375). Interestingly, CRF01_AE is the predominant circulating strain in Thailand, where the RV144 trial took place. In this trial, which resulted in a modest degree of protection, ADCC responses were identified as being part of the correlate of protection. Here we investigate the influence of the Phe 43 cavity on ADCC responses. Filling this cavity with a histidine or tryptophan residue in Env with a natural serine residue at this position (S375H/W) increased the susceptibility of HIV-1-infected cells to ADCC. Conversely, the replacement of His 375 by a serine residue (H375S) within HIV-1 CRF01_AE decreased the efficiency of the ADCC response. Our results raise the intriguing possibility that the presence of His 375 in the circulating strain where the RV144 trial was held contributed to the observed vaccine efficacy. HIV-1-infected cells presenting Env in the CD4-bound conformation on their surface are preferentially targeted by ADCC mediated by HIV-positive (HIV) sera. Here we show that the gp120 Phe 43 cavity modulates the propensity of Env to sample this conformation and therefore affects the susceptibility of infected cells to ADCC. CRF01_AE HIV-1 strains have an unusual Phe 43 cavity-filling His 375 residue, which increases the propensity of Env to sample the CD4-bound conformation, thereby increasing susceptibility to ADCC.
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http://dx.doi.org/10.1128/JVI.02452-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355605PMC
April 2017

Response to Tenofovir Among Lamivudine-experienced Hepatitis B and HIV-coinfected Adolescents.

Pediatr Infect Dis J 2017 04;36(4):401-404

From the *Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; †Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ‡Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand: §Nakornping Hospital, Chiang Mai, Thailand; ¶The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), the Thai Red Cross AIDS Research, Bangkok, Thailand; and ‖Department of Pediatrics, Faculty of Medicine, and Research Unit in Pediatric Infectious Diseases and Vaccines, Chulalongkorn University, Bangkok, Thailand.

We determined hepatitis B virus (HBV) suppression rates among 18 lamivudine (3TC)-experienced HBV-human immunodeficiency virus-coinfected adolescents after treatment with tenofovir disoproxil fumurate (TDF). At TDF initiation, their median age was 17.6 years, and duration of 3TC exposure was 7.3 years. Eleven patients (61%) achieved HBV DNA <60 IU/mL after 48 weeks on TDF and 3TC which was similar to adult studies, although hepatitis B surface antigen loss or hepatitis B envelope antigen seroconversion did not occur.
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http://dx.doi.org/10.1097/INF.0000000000001491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348266PMC
April 2017

Impact of tenofovir disoproxil fumarate on bone metabolism and bone mass among perinatally HIV-infected Asian adolescents.

Antivir Ther 2017 27;22(6):471-479. Epub 2016 Oct 27.

HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: This study aimed to determine the effect of tenofovir disoproxil fumarate (TDF) on bone metabolism and bone mass in HIV-infected adolescents.

Methods: This was a sub-study of a cross-sectional multicentre bone health trial that enrolled perinatally HIV-infected Thai and Indonesian adolescents (10-18 years) with viral suppression on antiretroviral therapy. Participants were classified into two groups as TDF users and non-users. Bone metabolism-related markers (25-hydroxyvitamin D [25-OHD], intact parathyroid hormone [iPTH], bone turnover biomarkers), and lumbar spine dual-energy X-ray absorptiometry were assessed. Bone mineral density (BMD)/bone mineral apparent density (BMAD) Z-scores were calculated.

Results: Of 394 adolescents, 136 (34.5%) and 258 (65.5%) were TDF users and non-users, respectively. Among TDF users, median age (IQR) was 16.1 (14.7-17.4) years and TDF treatment duration (IQR) was 2.3 (1.4-3.1) years. Among TDF non-users, median age (IQR) was 14.3 (12.6-16.4) years. BMD and BMAD Z-scores comparing TDF users with non-users were -0.8 and -0.6 (P=0.27), and -0.3 and -0.2 (P=0.58), respectively. The association between TDF use and iPTH elevation was intensified in adolescents with suboptimal vitamin D levels (25-OHD <30 ng/ml; P=0.001). TDF administration was positively associated with bone resorption marker (P=0.04) and negatively associated with bone formation marker (P=0.04). With data up to 4 years, neither association between TDF use and bone mass loss (BMD: P=0.09; BMAD: P=0.22), nor variation of bone mass Z-scores by TDF treatment duration (BMD: P=0.34; BMAD: P=0.58) was demonstrated.

Conclusions: Recent TDF administration was correlated with PTH elevation and bone turnover dysregulation but not with bone mass reduction in our cohort. A study with extended follow-up to ascertain TDF-associated bone mass deterioration is warranted.
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http://dx.doi.org/10.3851/IMP3103DOI Listing
July 2018

Impact of orphan status on HIV treatment outcomes and retention in care of children and adolescents in Asia.

J Virus Erad 2016 Oct 5;2(4):227-231. Epub 2016 Oct 5.

TREAT Asia/amfAR - The Foundation for AIDS Research , Bangkok , Thailand .

An analysis of the impact of orphanhood at antiretroviral therapy (ART) initiation on HIV outcomes in Asia included 4300 children; 51% were male. At ART initiation, 1805 (42%) were non-orphans (median age: 3 years), 1437 (33%) were single orphans (6 years) and 1058 (25%) were double orphans (7 years). Ten-year post-ART survival was 93.4-95.2% across orphan categories. Clinic transfers were higher among single and double orphans than non-orphans (41% 11%, <0.001). On multivariate analysis, children ≥3 years at ART initiation (hazard ratio 1.58 <3 years, 95% confidence interval: 1.11-2.24) were more likely to be lost to follow-up. Although post-ART mortality and retention did not differ by orphan status, orphans were at greater risk of starting ART at older ages, and with more severe immunosuppression and poorer growth.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075350PMC
October 2016

Rilpivirine as a Treatment for HIV-infected Antiretroviral-naïve Adolescents: Week 48 Safety, Efficacy, Virology and Pharmacokinetics.

Pediatr Infect Dis J 2016 Nov;35(11):1215-1221

From the *Josha Research, Bloemfontein, South Africa; †HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‡St Jude Children's Research Hospital, Memphis, Tennessee; §Kasturba Medical College Hospital, Mangalore, India; ¶Joint Clinical Research Centre, Kampala, Uganda; and ‖Janssen Pharmaceutica NV, Beerse, Belgium.

Background: Rilpivirine 25 mg qd yields similar exposure in adolescents and adults (Pediatric study in Adolescents Investigating a New NNRTI TMC278 [PAINT] Cohort 1, Part 1). We report rilpivirine safety, efficacy, virology and pharmacokinetics in adolescents during 48 weeks of treatment (Cohort 1, Part 2).

Methods: PAINT (NCT00799864) is a phase II, ongoing, open-label, single-arm trial of rilpivirine plus 2 investigator-selected nucleoside/nucleotide reverse-transcriptase inhibitors. Cohort 1 of PAINT includes treatment-naïve HIV-1-infected adolescents (≥12 to <18 years). Following approval in adults and after Part 1a in Cohort 1, enrollment was restricted to screening viral load (VL) ≤100,000 copies/mL.

Results: Overall, 20 (56%) of 36 patients were women, 18 (50%) were aged ≥12 to <15 years, 32 (89%) were Black or African American, mostly from South Africa or Uganda, and 28 (78%) had baseline VL ≤100,000 copies/mL. At week 48, adverse events considered possibly related to treatment occurred in 13 (36%) patients, mostly (excluding investigations) somnolence (n = 5, 14%) and nausea (n = 2, 6%). Most adverse events were grade 1 or 2, and 7 (19%) patients had grade 3 or 4 adverse events. Week 48 virologic response (VL <50 copies/mL, time-to-loss-of-virologic-response) was achieved in 26 of the 36 (72%) patients: 22 of the 28 (79%) with baseline VL ≤100,000 copies/mL and 4 of the 8 (50%) with baseline VL >100,000 copies/mL. Median (range) CD4 count increased by 184 (-135 to 740) cells/mm at week 48. Eight patients experienced virologic failure, including 5 who developed rilpivirine resistance-associated mutations, mostly E138K, K101E and M230L. Mean (standard deviation) rilpivirine area-under-the-concentration-time curve from 0 to 24 hours (AUC24h and C0h) were 2391 (991) ng·h/mL and 83.5 (38.7) ng/mL, respectively.

Conclusions: Rilpivirine safety, virologic and pharmacokinetic profiles were similar in treatment-naïve HIV-1-infected adolescents and adults, supporting use of rilpivirine 25 mg qd, plus other antiretrovirals, in treatment-naïve adolescents with VL ≤100,000 copies/mL at treatment initiation.
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http://dx.doi.org/10.1097/INF.0000000000001275DOI Listing
November 2016

Contraceptive challenges in adolescents living with or at risk of HIV.

J Virus Erad 2016 Apr 1;2(2):82-6. Epub 2016 Apr 1.

Faculty of Medicine , Chulalongkorn University , Bangkok , Thailand.

Many adolescents living with or without HIV are sexually active and in need of continuous free access to a variety of contraceptive methods. Dual contraception, condom use together with reversible effective contraception (hormonal contraception [HC] or intrauterine device), seems to be the most effective option for female adolescents for protection from unintended pregnancy and sexually transmitted infections. When counselling on specific contraceptive choice, healthcare providers should be aware about possible interactions of some types of HC with the immune system, with possible changes in infectivity, as well as about drug interactions between mainly efavirenz and some types of progestins. Adding HC to HIV-positive status and antiretroviral therapy could have additive effects on metabolism. At the same time, the possible disadvantages of using HC in women living with HIV should be balanced against the advantages of very reliable methods of preventing unintended pregnancies. To reach and deliver a contraceptive service to more young women, it has proven effective to organise adolescent-friendly clinics and/or integrate them with HIV services. Diverse approaches, including community-based contraceptive service provision and the use of modern technologies, can complement the effort of providing contraceptive services to this target group of female adolescents living with HIV or at risk of HIV.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965250PMC
April 2016

Early Height and Weight Changes in Children Using Cotrimoxazole Prophylaxis With Antiretroviral Therapy.

Clin Infect Dis 2016 11 28;63(9):1236-1244. Epub 2016 Jul 28.

The Kirby Institute, University of New South Wales, Sydney, Australia.

Background: The growth benefits of cotrimoxazole during early antiretroviral therapy (ART) are not well characterized.

Methods: Individuals enrolled in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database were included if they started ART at ages 1 month-14 years and had both height and weight measurements available at ART initiation (baseline). Generalized estimating equations were used to identify factors associated with change in height-for-age z-score (HAZ), follow-up HAZ ≥ -2, change in weight-for-age z-score (WAZ), and follow-up WAZ ≥ -2.

Results: A total of 3217 children were eligible for analysis. The adjusted mean change in HAZ among cotrimoxazole and non-cotrimoxazole users did not differ significantly over the first 24 months of ART. In children who were stunted (HAZ < -2) at baseline, cotrimoxazole use was not associated with a follow-up HAZ ≥ -2. The adjusted mean change in WAZ among children with a baseline CD4 percentage (CD4%) >25% became significantly different between cotrimoxazole and non-cotrimoxazole users after 6 months of ART and remained significant after 24 months (overall P < .01). Similar changes in WAZ were observed in those with a baseline CD4% between 10% and 24% (overall P < .01). Cotrimoxazole use was not associated with a significant difference in follow-up WAZ in children with a baseline CD4% <10%. In those underweight (WAZ < -2) at baseline, cotrimoxazole use was associated with a follow-up WAZ ≥ -2 (adjusted odds ratio, 1.70 vs not using cotrimoxazole [95% confidence interval, 1.28-2.25], P < .01). This association was driven by children with a baseline CD4% ≥10%.

Conclusions: Cotrimoxazole use is associated with benefits to WAZ but not HAZ during early ART in Asian children.
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http://dx.doi.org/10.1093/cid/ciw514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064162PMC
November 2016