Immunologic and virologic failure after first-line NNRTI-based antiretroviral therapy in Thai HIV-infected children

<p>Abstract</p> <p>Background</p> <p>There are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined the incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART.</p> <p>Methods</p> <p>Antiretroviral (ART)-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%≥25%. IF was defined as persistent decline of ≥5% in CD4% in children with CD4%<15% at baseline or decrease in CD4 count ≥30% from baseline. VF was defined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF.</p> <p>Results</p> <p>107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. Baseline data were median (IQR) age 6.2 (4.2-8.9) years, CD4% 7 (3-15), HIV-RNA 5.0 (4.9-5.5) log₁₀copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively.</p> <p>At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and CD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of children had immune recovery (CD4%≥25%) and 75% of children had HIV-RNA <1.7log₁₀copies/ml.</p> <p>Thirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in the first 24 and 48 weeks respectively.</p> <p>Only 1 (0.9%) child experienced IF within 96 weeks and the sensitivity (95%CI) of IF to VF was 4 (0.1-20.4)% and specificity was 100 (93.9-100)%.</p> <p>Conclusion</p> <p>Immunologic failure, as defined here, had low sensitivity compared to VF and should not be recommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to detect early treatment failure.</p> <p>Trial Registration</p> <p><b>Clinicaltrials.gov identification number </b><a href="http://www.clinicaltrials.gov/ct2/show/NCT00476606">NCT00476606</a></p

A feasibility study of immediate versus deferred antiretroviral therapy in children with HIV infection

<p>Abstract</p> <p>Objective</p> <p>To evaluate the feasibility of a large immediate versus deferred antiretroviral therapy (ART) study in children.</p> <p>Methods</p> <p>We conducted an open-label pilot randomized clinical trial study in 43 Thai children with CD4 15 to 24% of starting generic AZT/3TC/NVP immediately (Arm 1) or deferring until CD4 < 15% or CDC C (Arm 2). Primary endpoints were recruitment rate, adherence to randomized treatment and retention in trial. Secondary endpoints were % with CDC C or CD4 < 15%. Children were in the trial until the last child reached 108 weeks. Intention to treat and on treatment analyses were performed.</p> <p>Results</p> <p>Recruitment took 15 months. Twenty-six of 69 (37.7%) were not eligible due mainly to low CD4%. Twenty four and 19 were randomized to arms 1 and 2 respectively. All accepted the randomized arm; however, 3 in arm 1 stopped ART and 1 in arm 2 refused to start ART. Ten/19 (53%) in arm 2 started ART. At baseline, median age was 4.8 yrs, CDC A:B were 36:7, median CD4 was 19% and viral load was 4.8 log. All in arm 1 and 17/19 in arm 2 completed the study (median of 134 weeks). No one had AIDS or death. Four in immediate arm had tuberculosis. Once started on ART, deferred arm children achieved similar CD4 and viral load response as the immediate arm. Adverse events were similar between arms. The deferred arm had a 26% ART saving.</p> <p>Conclusion</p> <p>Almost 40% of children were not eligible due mainly to low CD4% but adherence to randomized treatment and retention in trial were excellent. A larger study to evaluate when to start ART is feasible.</p

Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand

BACKGROUND: Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. METHODS: Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit. RESULTS: 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) 3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. CONCLUSION: Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months

From Transmission to Transition: Lessons Learnt from the Thai Paediatric Antiretroviral Programme

BACKGROUND: The Thai HIV programme is a leader in the public health approach to HIV treatment. Starting at transmission of HIV and ending with transition to adult services this paper assesses the paediatric HIV treatment continuum from three perspectives: service-user, provider and policy maker, to understand what works well and why. METHODS: A qualitative research design was used to assess and triangulate the stakeholder perspectives. Semi-structured interviews were conducted with ART service-users (n = 35), policy actors (n = 20); telephone interviews with prior caregivers of orphans (n = 10); and three focus group discussions with service-providers (hospital staff and volunteers) from a district, provincial and a university hospital. FINDINGS: Children accessing HIV care were often orphaned, cared for by elderly relatives and experiencing multiple vulnerabilities. Services were divided into three stages, 1. Diagnosis and linkage: Despite strong policies there were supply and demand-side gaps in the prevention of mother-to-child transmission 'cascade' preventing early diagnosis and/or treatment. 2. Maintenance on ART - Children did well on treatment; caregivers took adherence seriously and valued the quality of services. Drug resistance, adherence and psychosocial issues were important concerns from all perspectives. 3. Adolescents and transition: Adolescent service-users faced greater complexity in their physical and emotional lives for which providers lacked skills; transition from the security of paediatric clinic was a daunting prospect. Dedicated healthcare providers felt they struggled to deliver services that met service-users' diverse needs at all stages. Child- and adolescent-specific elements of HIV policy were considered low priority. CONCLUSIONS: Using the notion of the continuum of care a number of strengths and weaknesses were identified. Features of paediatric services need to evolve alongside the changing needs of service users. Peer-support volunteers have potential to add continuity and support at all stages. It is critical that adolescents receive targeted support, particularly during transition to adult services

Effectiveness of a Mobile App (KhunLook) Versus the Maternal and Child Health Handbook on Thai Parents’ Health Literacy, Accuracy of Health Assessments, and Convenience of Use: Randomized Controlled Trial

BackgroundChildren of parents who have higher health literacy (HL) benefit more from preventive child health care. Digital interventions have been used to improve parents’ HL with high satisfaction. KhunLook is a Thai mobile app conceived using strategies to improve HL. It was developed to assist parents in assessing and keeping track of their child’s health in complement to the standard Maternal and Child Health Handbook (MCHH). ObjectiveThis trial focuses on the effectiveness of using the KhunLook app with the MCHH and standard care (intervention) compared with the conventional MCHH and standard care (control) on parents’ HL. Data on accuracy of parents’ assessment of their child’s health and growth as well as convenience of use of the tool (app or MCHH) in the well-child clinic were collected at 2 visits (immediate=visit 1, and intermediate=visit 2). MethodsParents of children under 3 years of age who (1) had a smartphone or tablet and the MCHH and (2) could participate in 2 visits, 2-6 months apart at Srinagarind Hospital, Khon Kaen, Thailand, were enrolled in this 2-arm parallel randomized controlled trial between April 2020 and May 2021. Parents were randomized 1:1 to 2 groups. At visit 1, data on demographics and baseline HL (Thailand Health Literacy Scales) were collected. Parents in the app group used the KhunLook app and the control group used their child’s handbook to assess their child’s growth, development, nutrition and feeding, immunization status and rated the convenience of the tool they used. At visit 2, they repeated the assessments and completed the HL questionnaire. ResultsA total of 358 parents completed the study (358/408, 87.7%). After the intervention, the number of parents with high total HL significantly increased from 94/182 (51.6%) to 109/182 (59.9%; 15/182; Δ 8.2%; P=.04), specifically in the health management (30/182; Δ 16.4%; P<.001) and child health management (18/182; Δ 9.9%; P=.01) domains in the app group, but not in the control group. Parents in the app group could correctly assess their child’s head circumference (172/182, 94.5% vs 124/176, 70.5%; P<.001) and development (173/182, 95.1% vs 139/176, 79.0%; P<.001) better than those in the control group at both visits. A higher proportion of parents in the app group rated their tool as very easy or easy to use (174-181/182, 95.6%-99.5% vs 141-166/176, 80.1%-94.3%; P<.001) on every item since the first visit. ConclusionsOur results suggest the potential of a smartphone app (KhunLook) to improve parents’ HL as well as to promote superior accuracy of parents’ assessment of their child’s head circumference and development, with a similar effect on weight, height, nutrition and feeding, and immunization as in traditional interventions. Using the KhunLook app is useful and more convenient for parents in promoting a healthy child preventive care during early childhood. Trial RegistrationThai Clinical Trials Registry TCTR20200312003; https://www.thaiclinicaltrials.org/show/TCTR2020031200

Mortality and Comorbidities in Extremely Low Birth Weight Thai Infants: A Nationwide Data Analysis

This is the first nationwide study aimed to evaluate in-hospital mortality and comorbidities of extremely low birth weight (ELBW) infants in Thailand between 2015&ndash;2020. Data of ELBW infants were collected from the National Health Coverage Scheme. The incidence of ELBW Thai infants was 1.75 per 1000 live births. Sixty-five percent of ELBW infants were delivered in tertiary-care facilities, with 63% surviving until discharge. In-hospital mortality was 36.9%. Non-invasive respiratory supports were documented in just 17.6% of the study population, whereas total parenteral nutrition was used in 52.3% of neonates. There were several comorbidities, with the three most frequent including respiratory distress syndrome (70.7%), neonatal jaundice (66.7%), and sepsis (60.4%). The median hospitalization cost for one ELBW infant who survived was 296,438.40 baht ($8719). Conclusion: Thailand had an acceptable ELBW infant survival rate (63%), but comorbidities remained particularly severe and cost one hundred times the median hospital cost for one ELBW infant that survived in comparison to a normal newborn infant. Better health outcomes require strategies to raise awareness of the issues and the appropriate implementation of evidence-based solutions, particularly improving neonatal care facilities, as well as early referral of high-risk pregnant women and neonates, which will aid in the future reduction of neonatal morbidities and mortalities

Early‑onset neonatal sepsis and antibiotic use in Indonesia: a descriptive, cross‑sectional study

Background: Early diagnosis and prompt antibiotic treatment are crucial to reducing morbidity and mortality of early-onset sepsis (EOS) in neonates. However, this strategy remains challenging due to non-specific clinical findings and limited facilities. Inappropriate antibiotics use is associated with ineffective therapy and adverse outcomes. This study aims to determine the characteristics of EOS and use of antibiotics in the neonatal-intensive care units(NICUs) in Indonesia, informing efforts to drive improvements in the prevention, diagnosis, and treatment of EOS. Methods: A descriptive study was conducted based on pre-intervention data of the South East Asia-Using Research for Change in Hospital-acquired Infection in Neonates project. Our study population consisted of neonates admit- ted within 72 h of life to the three participating NICUs. Neonates who presented with three or more clinical signs or laboratory results consistent with sepsis and who received antibiotics for 5 consecutive days were considered to have EOS. Culture-proven EOS was defined as positive blood or cerebrospinal fluid culture. Type and duration of antibiotics used were also documented. Results: Of 2,509 neonates, 242 cases were suspected of having EOS (9.6%) with culture-proven sepsis in 83 cases (5.0% of neonatal admissions in hospitals with culture facilities). The causative organisms were mostly gram-negative bacteria (85/94; 90.4%). Ampicillin / amoxicillin and amikacin were the most frequently prescribed antibiotics in hospi- tals with culture facilities, while a third-generation cephalosporin was mostly administered in hospital without culture facilities. The median durations of antibiotic therapy were 19 and 9 days in culture-proven and culture-negative EOS groups, respectively. Conclusions: The overall incidence of EOS and culture-proven EOS was high in Indonesia, with diverse and pro- longed use of antibiotics. Prospective antibiotic surveillance and stewardship interventions are required

Adherence to antiretroviral therapy, stigma and behavioral risk factors in HIV-infected adolescents in Asia

We studied behavioral risks among HIV-infected and uninfected adolescents using an audio computer-assisted self-interview. A prospective cohort study was initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected adolescents were matched to uninfected adolescents (4:1) by sex and age group (12-14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5 years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1 years) adolescents. At enrollment, HIV-infected adolescents were on antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14% had HIV-RNA >1000 copies/mL; 19% reported adherence 1000 copies/mL. Risk behaviors were common among adolescents, with few differences between those with and without HI

Alcohol use, suicidality and virologic non‐suppression among young adults with perinatally acquired HIV in Thailand: a cross‐sectional study

Abstract Introduction Young adults with perinatally acquired HIV (YA‐PHIV) are facing transitions to adult life. This study assessed health risk behaviours (including substance use), mental health, quality of life (QOL) and HIV treatment outcomes of Thai YA‐PHIV. Methods A cross‐sectional study was conducted in Thai YA‐PHIV aged 18–25 years who were enrolled in a prospective cohort study at five tertiary paediatric HIV care centres in Thailand. Study data were obtained through face‐to‐face interviews from November 2020 to July 2021. Assessments were performed for alcohol use (Alcohol Use Disorders Identification Test; AUDIT), smoking (Fagerstrom Test for Nicotine Dependence), drug/substance use (Drug Abuse Screening Test; DAST‐10), depression (Patient Health Questionnaire for Adolescents; PHQ‐A), anxiety (Generalized Anxiety Disorder; GAD‐7) and QOL (World Health Organization QOL Brief‐Thai). HIV treatment outcomes were extracted from the National AIDS Program database. Results Of 355 YA‐PHIV, 163 (46%) were males: their median age was 21.7 (interquartile range, IQR 20.2–23.5) years. There were 203 YA‐PHIV (58%) who reported ever having sex; 141 (40%) were sexually active in the past 6 months, of whom 86 (61%) reported 100% condom use. Overall, 49 (14%) met the criteria for harmful alcohol use; 28 (7.9%) were alcohol dependent. Sixty (17%) were current smokers and 37 (11%) used drugs/substances. The frequency of moderate up to severe symptoms for depression was 18% and for anxiety was 9.7%. Their overall QOL was good in 180 (51%), moderate in 168 (47%) and poor in five (1.4%). There were 49 YA‐PHIV (14%) with CD4 200 copies/ml). On multivariate analyses, the highest education at the primary to high school or vocational school levels (adjusted odds ratio [aOR] 2.02, 95% CI 1.40–3.95, p 0.04), harmful alcohol use (aOR 2.48, 95% CI 1.24–4.99, p 0.01), alcohol dependence (aOR 3.54, 95% CI 1.51–8.31, p <0.01) and lifetime suicidal attempt (aOR 2.66, 95% CI 1.11–6.35, p 0.03) were associated with non‐suppression. Conclusions Regular screening for alcohol use and mental health, including suicidality, would be useful to identify YA‐PHIV who need more intensive psychosocial support or referral services to ensure they can achieve and maintain a high QOL into adult life