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Fulltext Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy in Perinatally HIV-Infected, Treatment-Naïve Adolescents in Asia

Boettiger DC, Sudjaritruk T, Nallusamy R, Lumbiganon P, Rungmaitree S, Hansudewechakul R, et al.

J Adolesc Health, 2016 Apr;58(4):451-459.
PMID: 26803201 DOI: 10.1016/j.jadohealth.2015.11.006

PURPOSE: About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population.
METHODS: Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL.
RESULTS: Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count ≤200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure.
CONCLUSIONS: Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.
Fulltext Outcomes of human immunodeficiency virus-infected children after anti-retroviral therapy in Malaysia

Moy FS, Fahey P, Nik Yusoff NK, Razali KA, Nallusamy R, TREAT Asia Pediatric HIV Observational Database (TApHOD)

J Paediatr Child Health, 2015 Feb;51(2):204-8.
PMID: 25142757 DOI: 10.1111/jpc.12712

To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART).
Fulltext Prevalence and incidence of liver dysfunction and assessment of biomarkers of liver disease in HIV-infected Asian children

Aurpibul L, Bunupuradah T, Sophan S, Boettiger D, Wati DK, Nguyen LV, et al.

Pediatr Infect Dis J, 2015 Jun;34(6):e153-8.
PMID: 25970117 DOI: 10.1097/INF.0000000000000693

We determined the prevalence and incidence of liver dysfunction before and after initiation of combination antiretroviral therapy (cART) in the TREAT Asia Pediatric HIV Observational Database.
Fulltext Short Communication: Impact of Viral Load Use on Treatment Switch in Perinatally HIV-Infected Children in Asia

Jamal Mohamed T, Teeraananchai S, Kerr S, Phongsamart W, Nik Yusoff NK, Hansudewechakul R, et al.

AIDS Res Hum Retroviruses, 2017 03;33(3):230-233.
PMID: 27758114 DOI: 10.1089/AID.2016.0039

We sought to assess the impact of routine HIV viral load (VL) monitoring on the incidence of switching from a first- to a second-line antiretroviral therapy (ART) regimen, and to describe factors associated with switch. Data from a regional cohort of 16 clinical programs in six Asian countries were analyzed. Second-line switch was defined as a change from a non-nucleoside reverse transcriptase inhibitor (NNRTI) to a protease inhibitor (PI) or vice versa, and ≥1 of the following: (1) reported treatment failure by local criteria, (2) switch of ≥1 additional drug, or (3) a preceding HIV VL ≥1,000 copies/ml. Routine VL was having ≥1 test after ≥24 weeks of ART and ≥1 time/year thereafter. Factors associated with time to switch were evaluated with death and loss to follow-up as competing risks. A total of 2,398 children were included in this analysis. At ART initiation, the median (interquartile range) age was 6.0 (3.3-8.9) years, more than half had WHO stage 3 or 4, the median CD4 was 189 (47-456) cells/mm3, 93% were on NNRTI-based first-line ART, and 34% had routine VL monitoring. Treatment switch occurred in 17.6% of patients, at a median of 35 (22-49) months. After adjusting for country, sex, first ART regimen, and CD4% at ART initiation, children with routine VL monitoring were 1.46 (95% confidence interval 1.11-1.93) times more likely to be switched (p = .007). Scale-up of VL testing will lead to earlier identification of treatment failure, and it can help guide earlier switches to prevent resistance.
The long-term outcomes of antiretroviral treatment initiated with mono or dual nucleoside reverse transcriptase inhibitors in HIV-1-infected children: an Asian observational study

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.
Fulltext Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Ballif M, Renner L, Claude Dusingize J, Leroy V, Ayaya S, Wools-Kaloustian K, et al.

J Pediatric Infect Dis Soc, 2015 Mar;4(1):30-8.
PMID: 26407355 DOI: 10.1093/jpids/piu020

BACKGROUND: The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge.
METHODS: We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study.
RESULTS: Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children.
CONCLUSIONS: Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected children.
Fulltext Use and Outcomes of Antiretroviral Monotherapy and Treatment Interruption in Adolescents With Perinatal HIV Infection in Asia

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.
Fulltext Weight as predictors of clinical progression and treatment failure: results from the TREAT Asia Pediatric HIV Observational Database

Kariminia A, Durier N, Jourdain G, Saghayam S, Do CV, Nguyen LV, et al.

J Acquir Immune Defic Syndr, 2014 Sep 01;67(1):71-6.
PMID: 24872132 DOI: 10.1097/QAI.0000000000000227

OBJECTIVE: To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART).
METHODS: We used Cox regression to analyze data of a cohort of Asian children.
RESULTS: A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score < -3 was associated with mortality (P < 0.001) independent of CD4% and < -2 was associated with immunological failure (P ≤ 0.03) independent of age at cART.
CONCLUSIONS: Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings.
Fulltext X-linked chronic granulomatous disease in a male child with an X-CGD carrier, Klinefelter brother

Gill HK, Kumar HC, Cheng CK, Ming CC, Nallusamy R, Yusoff NM, et al.

Asian Pac J Allergy Immunol, 2013 Jun;31(2):167-72.
PMID: 23859418 DOI: 10.12932/AP0274.31.2.2013

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency (PID) caused by a dysfunctional respiratory burst enzyme NADPH-oxidase. The concurrence of Klinefelter’s Syndrome (KS) and CGD would be extremely rare.
OBJECTIVE: We describe the study of a family where the youngest male child had X-linked CGD (X-CGD) while his older brother was both an X-CGD carrier and a Klinefelter.
METHODS: Flow cytometry was used to study respiratory burst and gp91-phox expression, while genetic investigation was done by RT-PCR, PCR and X-chromosome short tandem repeat (X-STR) analysis.
RESULTS: The Dihydrorhodamine (DHR) assay showed the patient’s neutrophils failed to produce a respiratory burst, while both the mother and an older brother showed a bimodal response. gp91-phox expression was absent in the patient’s neutrophils, and bimodal in the mother’s and brother’s neutrophils. The patient’s cDNA showed a C>T change at nucleotide 676 of the CYBB gene. The same change was seen in the patient’s gDNA, while the brother and mother were heterozygous, with C and T, in this position. The c.676C>T is a nonsense mutation that leads to premature termination of the gp91-phox protein. The brother karyotyped as 47, XXY and X chromosome analysis showed that he had inherited both his mother’s X chromosomes.
CONCLUSIONS: This study showed that the patient had gp91-phox deficient CGD while his older brother was a CGD carrier and a Klinefelter, who had inherited both his mother’s X chromosomes. This is the first report of such a concurrence in an individual, and argues for family members to be included in PID studies.
Key words: Chronic granulomatous disease, CYBB, gp91-phox, Klinefelter’s syndrome NADPHoxidase