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  1. Sohn AH, Chokephaibulkit K, Lumbiganon P, Hansudewechakul R, Gani YM, Van Nguyen L, et al.
    J Adolesc Health, 2020 01;66(1):92-99.
    PMID: 31627925 DOI: 10.1016/j.jadohealth.2019.07.025
    PURPOSE: The aim of this article was to study the clinical and social outcomes of health care transition among Asian adolescents and young adults with HIV (AYHIV).

    METHODS: AYHIV who transferred from a pediatric to an adult clinic within the past year across five sites in Malaysia, Thailand, and Vietnam had clinical and laboratory evaluations and completed questionnaires about their health, socioeconomic factors, and transition experiences. Multiple logistic regression was used to assess associations with HIV viremia.

    RESULTS: Of 93 AYHIV enrolled between June 2016 and April 2017, 56% were female, 87% acquired HIV through perinatal exposure, median age was 20 years (interquartile range [IQR] 18.5-21). Two-thirds were in a formal education program, 43% were employed, 43% of females and 35% of males were sexually active. Median lifetime antiretroviral therapy duration was 6.2 years (IQR 3.3-10.7); 45% had received second-line therapy. Median CD4 was 601 cells/mm3 (IQR 477-800); 82% had HIV-RNA <40 copies/mL. Being in a relationship, a shorter posttransition duration, self-reported adherence of ≥95%, and higher CD4 were inversely associated with HIV viremia. Half felt very prepared for the transfer to adult care, and 20% frequently and 43% sometimes still met with pediatric providers. Two-thirds reported needing to keep their HIV a secret, and 23%-38% reported never or rarely having someone to discuss problems with.

    CONCLUSIONS: Asian AYHIV in our cohort were concerned about the negative social impact of having and disclosing HIV, and one-third lacked people they could trust with their personal problems, which could have negative implications for their ability to navigate adult life.

  2. Wittawatmongkol O, Mohamed TJ, Le TP, Ung V, Maleesatharn A, Hansudewechakul R, et al.
    Journal of virus eradication, 2015 06 30;1(3):192-195.
    PMID: 27076917
    After a median of 115.9 months of follow-up, 90% of 206 HIV-1-infected children in a cohort in Asia who initiated antiretroviral treatment (ART) with mono or dual nucleoside reverse transcriptase inhibitors were alive and had comparable immunological and virological outcomes as compared to the 1,915 children who had started with highly active antiretroviral regimens. However, these children had higher rates of treatment-related adverse events, opportunistic infections, and cumulative mortality, and were more likely to require protease inhibitor-containing regimens or other more novel ART-based regimens.
  3. Bartlett AW, Truong KH, Songtaweesin WN, Chokephaibulkit K, Hansudewechakul R, Ly PS, et al.
    AIDS, 2018 07 31;32(12):1689-1697.
    PMID: 29794827 DOI: 10.1097/QAD.0000000000001883
    OBJECTIVES: The aim of this study was to describe characteristics of perinatally HIV-infected adolescents (PHIVAs), factors associated with mortality, and outcomes at transition.

    DESIGN: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia.

    METHODS: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation.

    RESULTS: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% had CD4+ cell count less than 500 cells/μl and 51.1% had experienced a WHO stage III/IV clinical event. At transition, 38.9% had CD4+ cell count less than 500 copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality rate was 0.71 per 100 person-years, with HIV RNA ≥1000 copies/ml, CD4+ cell count less than 500 cells/μl, height-for-age or weight-for-age z-score less than -2, history of a WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART.

    CONCLUSION: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition.

  4. Sudjaritruk T, Boettiger DC, Nguyen LV, Mohamed TJ, Wati DK, Bunupuradah T, et al.
    J Int AIDS Soc, 2019 06;22(6):e25312.
    PMID: 31179641 DOI: 10.1002/jia2.25312
    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 log10 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.

  5. Sohn AH, Lumbiganon P, Kurniati N, Lapphra K, Law M, Do VC, et al.
    AIDS, 2020 08 01;34(10):1527-1537.
    PMID: 32443064 DOI: 10.1097/QAD.0000000000002583
    OBJECTIVE: To implement a standardized cause of death reporting and review process to systematically disaggregate causes of HIV-related deaths in a cohort of Asian children and adolescents.

    DESIGN: Death-related data were retrospectively and prospectively assessed in a longitudinal regional cohort study.

    METHODS: Children under routine HIV care at sites in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam between 2008 and 2017 were followed. Causes of death were reported and then independently and centrally reviewed. Predictors were compared using competing risks survival regression analyses.

    RESULTS: Among 5918 children, 5523 (93%; 52% male) had ever been on combination antiretroviral therapy. Of 371 (6.3%) deaths, 312 (84%) occurred in those with a history of combination antiretroviral therapy (crude all-cause mortality 9.6 per 1000 person-years; total follow-up time 32 361 person-years). In this group, median age at death was 7.0 (2.9-13) years; median CD4 cell count was 73 (16-325) cells/μl. The most common underlying causes of death were pneumonia due to unspecified pathogens (17%), tuberculosis (16%), sepsis (8.0%), and AIDS (6.7%); 12% of causes were unknown. These clinical diagnoses were further grouped into AIDS-related infections (22%) and noninfections (5.8%), and non-AIDS-related infections (47%) and noninfections (11%); with 12% unknown, 2.2% not reviewed. Higher CD4 cell count and better weight-for-age z-score were protective against death.

    CONCLUSION: Our standardized cause of death assessment provides robust data to inform regional resource allocation for pediatric diagnostic evaluations and prioritization of clinical interventions, and highlight the continued importance of opportunistic and nonopportunistic infections as causes of death in our cohort.

  6. Bartlett AW, Sudjaritruk T, Mohamed TJ, Anugulruengkitt S, Kumarasamy N, Phongsamart W, et al.
    Clin Infect Dis, 2020 Jun 26.
    PMID: 32589711 DOI: 10.1093/cid/ciaa872
    BACKGROUND: Combination antiretroviral therapy (cART) failure is a major threat to HIV programs, with implications for individual- and population-level outcomes. Adolescents with perinatally-acquired HIV infection (PHIVA) should be a focus for treatment failure given their poorer outcomes compared to children and adults.

    METHODS: Data (2014-2018) from a regional cohort of Asian PHIVA who received at least 6 months of continuous cART were analyzed. Treatment failure was defined according to World Health Organization criteria. Descriptive analyses were used to report treatment failure and subsequent management and evaluate post-failure CD4 count and viral load trends. Kaplan-Meier survival analyses were used to compare the cumulative incidence of death and loss to follow-up (LTFU) by treatment failure status.

    RESULTS: A total 3,196 PHIVA were included in the analysis with a median follow-up period of 3.0 years, of whom 230 (7.2%) had experienced 292 treatment failure events (161 virologic, 128 immunologic, 11 clinical) at a rate of 3.78 per 100 person-years. Of the 292 treatment failure events, 31 (10.6%) had a subsequent cART switch within 6 months, which resulted in better immunologic and virologic outcomes compared to those who did not switch cART. The 5-year cumulative incidence of death and LTFU following treatment failure was 18.5% compared to 10.1% without treatment failure.

    CONCLUSIONS: Improved implementation of virologic monitoring is required to realize the benefits of virologic determination of cART failure. There is a need to address issues related to accessibility to subsequent cART regimens, poor adherence limiting scope to switch regimens, and the role of antiretroviral resistance testing.

  7. Bartlett AW, Mohamed TJ, Sudjaritruk T, Kurniati N, Nallusamy R, Hansudewechakul R, et al.
    Pediatr Infect Dis J, 2019 03;38(3):287-292.
    PMID: 30281549 DOI: 10.1097/INF.0000000000002208
    BACKGROUND: Perinatally HIV-infected adolescents (PHIVA) are exposed to a chronic systemic infection and long-term antiretroviral therapy (ART), leaving them susceptible to morbidities associated with inflammation, immunodeficiency and drug toxicity.

    METHODS: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria.

    RESULTS: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years.

    CONCLUSIONS: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.

  8. Bartlett AW, Lumbiganon P, Kurniati N, Sudjaritruk T, Mohamed TJ, Hansudewechakul R, et al.
    J Adolesc Health, 2019 11;65(5):651-659.
    PMID: 31395514 DOI: 10.1016/j.jadohealth.2019.05.025
    PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort.

    METHODS: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption.

    RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes.

    CONCLUSIONS: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.

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