Tavitiya Sudjaritruk

Successful treatment of a child with vascular pythiosis.

BackgroundHuman pythiosis is an emerging and life-threatening infectious disease caused by Pythium insidiosum. It occurs primarily in tropical, subtropical and temperate areas of the world, including Thailand. The aim of this report is to present the first pediatric case of typical vascular pythiosis.Case PresentationA 10-year-old boy with underlying β-thalassemia presented with gangrenous ulcers and claudication of the right leg which were unresponsive to antibiotic therapy for 6 weeks. Computerized tomography angiography indicated chronic arterial occlusion involving the right distal external iliac artery and its branches. High-above-knee amputation was urgently done to remove infected arteries and tissues, and to stop disease progression. Antibody to P. insidiosum was detected in a serum sample by the immunoblot and the immunochromatography tests. Fungal culture followed by nucleic sequence analysis was positive for P. insidiosum in the resected iliac arterial tissue. Immunotherapeutic vaccine and antifungal agents were administered. The patient remained well and was discharged after 2 months hospitalization without recurrence of the disease. At the time of this communication he has been symptom-free for 2 years.ConclusionsThe child presented with the classical manifestations of vascular pythiosis as seen in adult cases. However, because pediatricians were unfamiliar with the disease, diagnosis and surgical treatment were delayed. Both early diagnosis and appropriate surgical and medical treatments are crucial for good prognosis.

Immune reconstitution inflammatory syndrome from Penicillium marneffei in an HIV-infected child: a case report and review of literature

BackgroundsDisseminated Penicillium marneffei infection is one of the most common HIV-related opportunistic infections in Southeast Asia. Immune reconstitution inflammatory syndrome (IRIS) is a complication related to antiretroviral therapy (ART)-induced immune restoration. The aim of this report is to present a case of HIV-infected child who developed an unmasking type of IRIS caused by disseminated P. marneffei infection after ART initiation.Case presentationA 14-year-old Thai HIV-infected girl presented with high-grade fever, multiple painful ulcerated oral lesions, generalized non-pruritic erythrematous skin papules and nodules with central umbilication, and multiple swollen, warm, and tender joints 8 weeks after ART initiation. At that time, her CD4+ cell count was 7.2% or 39 cells/mm3. On admission, her repeated CD4+ cell count was 11% or 51 cells/mm3 and her plasma HIV-RNA level was < 50 copies/mL. Her skin biopsy showed necrotizing histiocytic granuloma formation with neutrophilic infiltration in the upper and reticular dermis. Tissue sections stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Grocott methenamine silver (GMS) stain revealed numerous intracellular and extracellular, round to oval, elongated, thin-walled yeast cells with central septation. The hemoculture, bone marrow culture, and skin culture revealed no growth of fungus or bacteria. Our patient responded well to intravenous amphotericin B followed by oral itraconazole. She fully recovered after 4-month antifungal treatment without evidence of recurrence of disease.ConclusionsIRIS from P. marneffei in HIV-infected people is rare. Appropriate recognition and properly treatment is important for a good prognosis.

ANTIBODY RESPONSES TO HEPATITIS A VIRUS VACCINATION IN THAI HIV-INFECTED CHILDREN WITH IMMUNE RECOVERY AFTER ANTIRETROVIRAL THERAPY

The prevalence of hepatitis A virus (HAV) protective antibody in 98 Thai HIV-infected children who achieved immune recovery after antiretroviral therapy was 12.2%. After a 2-dose HAV vaccination, 98.8% (85 of 86 children) seroconverted. The geometric mean titer was 520.95 mIU/mL. In a multivariate analysis, female gender, age <12 years and higher CD4 lymphocyte count at enrollment were predicting factors for high (≥250 mIU/mL) HAV antibody response.

Efficacy, safety and pharmacokinetics of tenofovir disoproxil fumarate in virologic-suppressed HIV-infected children using weight-band dosing.

Background: Tenofovir disoproxil fumarate (TDF) is approved for children but concerns remain about long-term renal and bone toxicity. We evaluated the efficacy, safety and pharmacokinetics of TDF in treatment-experienced children during 96 weeks. Methods: This was a prospective, open-label study in HIV-infected children 3–18 years of age (≥15 kg), with viral suppression on their first-line regimen without tenofovir. Children were given TDF/lamivudine/efavirenz once daily at entry; TDF was prescribed according to weight bands. Age-, gender- and CD4-matched controls receiving TDF-sparing regimens were concomitantly enrolled. Tenofovir pharmacokinetic assessment was performed at week 4. CD4 counts, HIV-1 RNA viral load and safety assessments were determined at baseline, 24, 48 and 96 weeks. Results: Eighty children were enrolled (40 per group); 35 (44%) were male. Median age was 12.2 (range 3.1–17.7) years. The median administered dose was 214 mg/m2. Tenofovir geometric mean AUC0–24 hours, Cmax and C24 hours were 2.66 [90% confidence interval (CI) 2.49–2.84] &mgr;g hours/mL, 0.26 (0.24–0.29) &mgr;g/mL and 0.057 (0.052–0.062) &mgr;g/mL, respectively. Estimated glomerular filtration rate did not significantly change overtime. The fractional excretion of calcium slightly increased but fractional excretion of phosphate was unchanged among children in TDF group. The bone mineral density Z score decreased in the first 24 weeks of TDF treatment and was stable afterward. The TDF group had lower cholesterol levels (P = 0.001). Thirty-nine of 40 children remained virologically suppressed. No serious adverse event related to tenofovir. Conclusion: TDF substitution in children and adolescents who were otherwise stable while receiving a first-line nonnucleoside reverse transcriptase inhibitor–based regimen achieved adequate exposure without clinically significant renal or bone adverse events over 96 weeks. While reassuring, these preliminary safety findings may not exclude delayed effects on renal function and bone density.

Immunogenicity and safety of monovalent influenza A (H1N1) 2009 in HIV-infected Thai children.

To evaluate the immunogenicity and safety of the monovalent pandemic influenza A (H1N1) 2009 (pH1N1) vaccine in HIV-infected Thai children, 2 doses, 28days apart, of non-adjuvant monovalent pH1N1 vaccine (Panenza(®) by Sanofi Pasteur, 15μg/dose) provided by the National Health Promotion Program of the Thai Ministry of Public Health were given to HIV-infected children. Immunogenicity was measured by hemagglutination inhibition test (HAI) using two antigens, pH1N1 (A/Thailand/104/09) and seasonal influenza A H1N1 (A/Brisbane/59/07-like), at baseline, and 28days after each dose. Serologic response was defined as four-fold rising of HAI titer or HAI titer ≥1:40 for those with baseline titer ≤1:10. Adverse events were recorded for 7days after each vaccination. Of the 119 HIV-infected children enrolled, 60 (50.4%) were female with a median (IQR) age of 10.4 (7.2-13.7)years. All but 2 (98.3%) children were receiving antiretroviral therapy. At baseline, the median CD4 cell count was 782 (570-1149)cells/mm(3), 91 (80.5%) children had HIV RNA level <40copies/ml. The baseline HAI titer ≥1:40 for pH1N1 and seasonal H1N1 were 45.4%, and 39.5%, respectively. At 28 days after doses 1 and 2, the serologic response rates for pH1N1 were 54.2% and 67.8% with the geometric mean titer of 109.9 and 141.8; and serologic response rate when tested with seasonal H1N1 were 2.5% and 3.5%, respectively. The presence of baseline HAI titer for pH1N1 or seasonal H1N1 was found to be associated with serologic response. The vaccine was well tolerated. The results suggested that monovalent pH1N1 vaccine was immunogenic and safe in well controlled HIV-infected children with low level of cross reacting antibody to seasonal H1N1.

Second-line protease inhibitor-based highly active antiretroviral therapy after failing non-nucleoside reverse transcriptase inhibitors-based regimens in Asian HIV-infected children

BACKGROUND The World Health Organization (WHO) recommends boosted protease inhibitor (bPI)-based HAART after failing non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. We examined outcomes of this regimen in Asian HIV-infected children. METHODS Children from five Asian countries in the TREAT Asia Pediatric HIV Observational Database (TApHOD) with ≥ 24 weeks of NNRTI-based HAART followed by ≥ 24 weeks of bPI-based HAART were eligible. Primary outcomes were the proportions with virological suppression (HIV RNA < 400 copies/ml) and immune recovery (CD4+ T-cell percentage [CD4%]≥ 25% if age < 5 years and CD4+ T-cell count ≥ 500 cells/mm3 if age ≥ 5 years) at 48 and 96 weeks. RESULTS Of 3,422 children, 153 were eligible; 52% were female. At switch, median age was 10 years, 26% were in WHO stage 4. Median weight-for-age z-score (WAZ) was -1.9 (n = 121), CD4% was 12.5% (n = 106), CD4+ T-cell count was 237 cells/mm3 (n = 112), and HIV RNA was 4.6 log10 copies/ml (n = 61). The most common bPI was lopinavir/ritonavir (83%). At 48 weeks, 61% (79/129) had immune recovery, 60% (26/43) had undetectable HIV RNA and 73% (58/79) had fasting triglycerides ≥ 130 mg/dl. By 96 weeks, 70% (57/82) achieved immune recovery, 65% (17/26) had virological suppression, and hypertriglyceridaemia occurred in 66% (33/50). Predictors for virological suppression at week 48 were longer duration of NNRTI-based HAART (P = 0.006), younger age (P = 0.007), higher WAZ (P = 0.020) and HIV RNA at switch < 10,000 copies/ml (P = 0.049). CONCLUSIONS In this regional cohort of Asian children on bPI-based second-line HAART, 60% of children tested had immune recovery by 1 year, and two-thirds had hyperlipidaemia, highlighting difficulties in optimizing second-line HAART with limited drug options.

Causes of first hospitalization among 1121 HIV-infected children: comparison of the pre-Pneumocystis jiroveci pneumonia prophylaxis, pre-antiretroviral therapy and antiretroviral therapy periods.

This study identified causes of first hospitalization among perinatally acquired HIV-infected children at Chiang Mai University Hospital between 1989 and 2009. Data were stratified into three seven-year time periods: pre-Pneumocystis jiroveci pneumonia (PJP) prophylaxis, pre-antiretroviral therapy (ART) and ART period. Over the 21-year study period, 1121 children were hospitalized. The mean age at admission was 2.7 years and had become older over time. Of the 1121 hospitalization causes, 50.6% were AIDS-defining illnesses (ADIs), 48.1% were non-AIDS-defining illnesses (NADIs) and 1.3% were related to immune reconstitution syndrome. Types of ADIs changed over time: PJP and recurrent Salmonella septicaemia decreased, while mycobacterial infection and systemic fungal infection increased. For NADIs, bacterial infections, viral infections and gastrointestinal problems decreased, but haematological problems increased in the third period. Decline in the number of hospitalizations and mortality rate, increase in the mean age of hospitalized children, change in the distribution of specific illnesses and appearance of immune reconstitution syndrome were observed in the ART period.

Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia.

Background:Data on pediatric treatment outcomes and drug resistance while on second-line antiretroviral therapy (ART) are needed to guide HIV care in resource-limited countries. Methods:HIV-infected children <18 years who were switched or switching to second-line ART after first-line failure were enrolled from 8 sites in Indonesia, Thailand, and Vietnam. Genotyping was performed at virologic failure (VF; HIV-RNA >1000 copies/mL). Cox proportional hazards regression was used to evaluate factors predicting VF. Results:Of 277 children, 41% were female. At second-line switch, age was 7.5 (5.3–10.3) years, CD4 count was 300 (146–562) cells per cubic millimeter, and percentage was 13 (7–20%); HIV-RNA was 5.0 (4.4–5.5) log10 copies per milliliter. Second-line regimens contained lamivudine (90%), tenofovir (43%), zidovudine or abacavir (30%), lopinavir (LPV/r; 91%), and atazanavir (ATV; 7%). After 3.3 (1.8–5.3) years on second-line ART, CD4 was 763 (556–1060) cells per cubic millimeter and 26% (20–31%). VF occurred in 73 (27%), with an incidence of 7.25 per 100 person-years (95% confidence interval [CI]: 5.77 to 9.12). Resistance mutations in 50 of 73 children with available genotyping at first VF included M184V (56%), ≥1 thymidine analogue mutation (TAM; 40%), ≥4 TAMs (10%), Q151M (4%), any major LPV mutation (8%), ≥6 LPV mutations (2%), and any major ATV mutation (4%). Associations with VF included age >11 years (hazard ratio [HR] 4.06; 95% CI: 2.15 to 7.66) and HIV-RNA >5.0 log10 copies per milliliter (HR 2.42; 95% CI: 1.27 to 4.59) at switch and were seen more commonly in children from Vietnam (HR 2.79; 95% CI: 1.55 to 5.02). Conclusions:One-fourth of children developed VF while on second-line ART. However, few developed major mutations to protease inhibitors.

Hypovitaminosis D and hyperparathyroidism: effects on bone turnover and bone mineral density among perinatally HIV-infected adolescents.

Objectives:The impact of hypovitaminosis D and secondary hyperparathyroidism on bone mineral density (BMD) in the setting of pediatric HIV infection remains unclear. This study aimed to determine the prevalence of hypovitaminosis D and hyperparathyroidism and their effects on bone turnover and BMD among HIV-infected adolescents in Southeast Asia. Design:A multicenter, cross-sectional study evaluating bone health and vitamin D metabolism in HIV-infected adolescents in Thailand and Indonesia. Methods:Perinatally HIV-infected adolescents aged 10–18 years on antiretroviral therapy with virologic suppression were enrolled. Serum 25-hydroxyvitamin D, intact parathyroid hormone, and bone turnover markers (C-terminal cross-linked telopeptide of type I collagen and procollagen type I amino-terminal propeptide) were assessed; serum 25-hydroxyvitamin D less than 20 ng/ml and intact parathyroid hormone more than 65 pg/ml were defined as hypovitaminosis D and hyperparathyroidism, respectively. Lumbar spine (L2–L4) BMD Z-score −2 or less was defined as low BMD. Results:Of 394 adolescents, 57% were women. The median age [interquartile range (IQR)] was 15.0 (13.3–16.9) years. The prevalence of hypovitaminosis D, hyperparathyroidism, and both conditions were 21% [95% confidence interval (CI): 17–25%], 17% (95% CI: 13–20%), and 5% (95% CI: 3–7%), respectively. Adolescents with hypovitaminosis D and secondary hyperparathyroidism had the highest median bone resorption (C-terminal cross-linked telopeptide of type I collagen: 1610 vs. 1270 ng/l; P = 0.04) and bone formation (procollagen type I amino-terminal propeptide: 572 vs. 330 &mgr;g/l; P = 0.02) markers, and the greatest proportion of low BMD (42 vs. 15%; P = 0.01) compared with the rest of the cohort. Conclusion:Hypovitaminosis D complicated with secondary hyperparathyroidism was associated with increased bone turnover and bone loss. Early treatment of hypovitaminosis D before hyperparathyroidism occurs may be important to prevent bone mass deterioration.

Vitamin D status in perinatally HIV-infected Thai children receiving antiretroviral therapy.

Abstract Background: Low vitamin D level is associated with adverse health outcomes and compromises HIV treatment response. We assess vitamin D status in HIV-infected Thai children receiving combination antiretroviral therapy (cART). Methods: A cross-sectional study in perinatally HIV-infected children. Vitamin D deficiency and vitamin D insufficiency were defined as serum 25-hydroxyvitamin D (25-OHD) level <20, and 21–29 ng/mL, respectively. Results: Eighty participants were enrolled. Their median age was 12.2 years. The median CD4 lymphocyte count was 784 cell/mm3; 95% had HIV RNA <50 copies/mL. The median (interquartile range, IQR) 25-OHD level was 33.5 (26.2–39.8) ng/mL. Thirty-four (43%) participants had low vitamin D level; 26 (33%) and 8 (10%) had vitamin D insufficiency and deficiency, respectively. In multivariate analysis, only geographic location was significantly associated with low vitamin D level. Conclusions: Most of perinatally HIV-infected children receiving cART had low vitamin D level. Calcium and vitamin D supplement might be beneficial.