Adverse bone health and abnormal bone turnover among perinatally HIV-infected Asian adolescents with virological suppression.

OBJECTIVES: This study aimed to determine the prevalence of low bone mass and assess its relationship with abnormal bone turnover among HIV-infected Asian adolescents. METHODS: A multicentre, cross-sectional study was conducted at four paediatric HIV centres in Thailand and Indonesia. Perinatally HIV-infected adolescents aged 10-18 years receiving antiretroviral therapy (ART) with virological suppression (HIV RNA < 400 copies/mL) were enrolled. Study assessments included lumbar spine (L2-L4) dual-energy X-ray absorptiometry and measurement of bone turnover markers. Bone mineral density (BMD) and bone mineral apparent density (BMAD) Z-scores were calculated based on Thai normative age- and sex-matched references. Low bone mass was defined as BMD or BMAD Z-scores ≤ -2. RESULTS: Of 396 participants, 57% were female. The median age was 15.0 [interquartile range (IQR) 13.3-16.9] years, and 73% were in Tanner stage 3-5. At enrolment, the median CD4 T-cell count was 734 (IQR 581-907) cells/µL, and 37% were on protease inhibitor (PI)-based regimens. The overall prevalence of lumbar spine BMD and BMAD Z-scores ≤ -2 were 16.4% and 8.3%, respectively. Z-scores were lower with older age, female sex, body mass index (BMI) <5th percentile, boosted PI exposure and CD4 T-cell percentage < 15% before ART initiation. Increased bone turnover markers were inversely associated with BMD and BMAD Z-scores. CONCLUSIONS: Low bone mass was linked to older age, female sex, low BMI, boosted PI exposure, and poor immunological status before ART commencement in our cohort of perinatally HIV-infected Asian adolescents. Dysregulation of bone turnover was associated with bone demineralization. Screening for low bone mass should be implemented to identify individuals who might benefit from interventions to preserve bone health.

Fatal Balamuthia amebic encephalitis in a healthy child: a case report with review of survival cases.

Balamuthia mandrillaris is one of the 4 amebas in fresh water and soil that cause diseases in humans. Granulomatous amebic encephalitis (GAE), caused by B. mandrillaris, is a rare but life-threatening condition. A 4-year-old, previously healthy, Thai girl presented with progressive headache and ataxia for over a month. Neuroimaging studies showed an infiltrative mass at the right cerebellar hemisphere mimicking a malignant cerebellar tumor. The pathological finding after total mass removal revealed severe necrotizing inflammation, with presence of scattered amebic trophozoites. Cerebrospinal fluid (CSF) obtained from lumbar puncture showed evidence of non-specific inflammation without identifiable organisms. A combination of pentamidine, sulfasalazine, fluconazole, and clarithromycin had been initiated promptly before PCR confirmed the diagnosis of Balamuthia amebic encephalitis (BAE). The patient showed initial improvement after the surgery and combined medical treatment, but gradually deteriorated and died of multiple organ failure within 46 days upon admission despite early diagnosis and treatment. In addition to the case, 10 survivors of BAE reported in the PubMed database were briefly reviewed in an attempt to identify the possible factors leading to survival of the patients diagnosed with this rare disease.

Correlation of selenium and zinc levels to antiretroviral treatment outcomes in Thai HIV-infected children without severe HIV symptoms.

BACKGROUND/OBJECTIVES: Deficiencies in antioxidants contribute to immune dysregulation and viral replication. To evaluate the correlation of selenium (Se) and zinc (Zn) levels on the treatment outcomes in HIV-infected children. SUBJECTS/METHODS: HIV-infected Thai children 1-12 years old, CD4 15-24%, without severe HIV symptoms were included. Se and Zn levels were measured by graphite furnace atomic absorption spectrometry at baseline and 48 weeks. Deficiency cutoffs were Se <0.1 µmol/l and Zn <9.9 µmol/l. Serum ferritin and C-reactive protein (CRP) were measured every 24 weeks. No micronutrient supplement was prescribed. RESULTS: In all, 141 children (38.3% male) with a median (interquartile range (IQR)) age of 7.3 (4.2-9.0) years were enrolled. Median baseline CD4% was 20%, HIV-RNA was 4.6 log(10)copies/ml. At baseline, median (IQR) Se and Zn levels were 0.9 (0.7-1.0) µmol/l and 5.9 (4.8-6.9) µmol/l, respectively. None had Se deficiency while all had Zn deficiency. Over 48 weeks, 97 initiated antiretroviral therapy (ART) and 81% achieved HIV-RNA <50 copies/ml with 11% median CD4 gain. The mean change of Se was 0.06 µmol/l (P=0.003) and Zn was 0.42 µmol/l (P=0.003), respectively. By multivariate analysis in children who received ART, predictors for greater increase of CD4% from baseline were lower baseline CD4% (P<0.01) and higher baseline Zn level (P=0.02). The predictors for greater decrease of HIV-RNA from baseline were higher baseline HIV-RNA and higher ferritin (both P<0.01). No association of CRP with the changes from baseline of CD4% or HIV-RNA was found. CONCLUSION: In HIV-infected Thai children without severe immune deficiency who commenced ART, no correlation between Se and ART treatment outcomes was found. Higher pre-ART Zn levels were associated with significant increases in CD4% at 48 weeks.

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.

HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess the prevalence, predictors and patterns of genotypic resistance mutations in children after failure of World Health Organization-recommended initial nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens. METHODS: We carried out a multicentre retrospective study of genotyping tests performed for all HIV-infected children at eight paediatric centres in Thailand who experienced failure of NNRTI therapy at a time when virological monitoring was not routinely available. RESULTS: One hundred and twenty children were included in the study. Their median age (interquartile range) was 9.1 (6.8-11.0) years, the median duration of their NNRTI regimens was 23.7 (15.7-32.6) months, their median CD4 percentage was 12% (4-20%), and their median plasma HIV RNA at the time of genotype testing was 4.8 (4.3-5.2) log(10) HIV-1 RNA copies/mL. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the Q151M complex, 5% had K65R, and 1% had the 69 insertion. Ninety-eight per cent of the children had at least one NNRTI resistance mutation, and 48% had etravirine mutation-weighted scores ≥4. CD4 percentage <15% prior to switching regimens [odds ratio (OR) 5.49; 95% confidence interval (CI) 2.02-14.93] and plasma HIV RNA>5 log(10) copies/mL (OR 2.46; 95% CI 1.04-5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion. CONCLUSIONS: In settings without routine viral load monitoring, second-line antiretroviral therapy regimens should be designed assuming that clinical or immunological failure is associated with high rates of multi-NRTI resistance and NNRTI resistance, including resistance to etravirine.

Low prevalence of insulin resistance among HIV-infected children receiving nonnucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy in Thailand.

BACKGROUND: Highly active antiretroviral therapy (HAART) is reported to cause insulin resistance among adults, but effects on children are less clear. We attempted to describe the prevalence of insulin resistance among HIV-infected children receiving HAART. METHODS: Insulin resistance was assessed at 96 weeks of treatment with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based HAART (nevirapine or efavirenz with stavudine and lamivudine) among children in Chiang Mai, Thailand. Insulin resistance was defined as homeostasis model assessment for insulin resistance (HOMA-IR) >/=3.16, fasting c-peptide >/=4.40 ng/mL or fasting insulin >/=25.0 muU/mL. Impaired fasting glucose (IFG) was defined as glucose >/=110 mg/dL. Measurements were analysed for associations with age, lipodystrophy, treatment regimen and clinical data. RESULTS: The prevalence of insulin resistance was 6.5%; no child had IFG. Those with insulin resistance were older with higher body mass index. Children >/=10 years had higher HOMA-IR, c-peptide and insulin, but no difference was seen in the frequency of insulin resistance. No associations between insulin resistance and lipodystrophy or treatment regimen were detected. CONCLUSIONS: Insulin resistance is uncommon among children receiving NNRTI-based HAART and is unrelated to lipodystrophy.

Haematological changes after switching from stavudine to zidovudine in HIV-infected children receiving highly active antiretroviral therapy.

OBJECTIVE: In resource-limited countries, stavudine (d4T) is commonly used as part of the initial highly active antiretroviral therapy (HAART) regimen. Many patients who subsequently develop lipodystrophy switch from d4T to zidovudine (ZDV), a drug that can be myelotoxic. We aimed to study the spectrum and severity of haematological changes following this substitution. METHODS: This was a retrospective cohort study. The inclusion criteria were as follows: HIV-infected children were included who (1) were 2-15 years old at the time of HAART initiation, (2) had not been diagnosed as having haematological diseases, (3) had been receiving a first HAART regimen consisting of either nevirapine or efavirenz, together with lamivudine and d4T, for at least 48 weeks and (4) had switched from d4T to ZDV at least 48 weeks previously. RESULTS: Seventy-eight children were included in the study. Thirty-six (46%) were male. The mean age was 10.3 years (standard deviation 3.1 years). The switch had been made a median time of 65 weeks (range 48-97 weeks) previously. There was no significant change in CD4 lymphocyte count or percentage, or HIV RNA level, after the switch. There was a statistically significant decrease in haemoglobin level (12.6 vs.12.1 g/dL; P<0.001), total white blood cell (WBC) count (8088 vs. 6910 cells/microL; P<0.001) and absolute neutrophil count (ANC) (4320 vs. 3448 cells/microL; P<0.001). However, the decreases never reached Division of AIDS grade 3 or 4 severity, and none of the patients had clinical symptoms or signs of anaemia, leukopenia, or neutropenia. No participant had to discontinue ZDV during the 48-week follow-up period. CONCLUSION: In a paediatric population, statistically significant decreases in haemoglobin level, WBC count and ANC occurred following the substitution of d4T with ZDV, but the magnitudes of the decreases were small and not clinically significant.

Prevalence of protective antibody against measles in HIV-infected children with immune recovery after highly active antiretroviral therapy.

OBJECTIVES: This study was conducted to determine the prevalence of measles-protective antibody in HIV-infected children with immune recovery after highly active antiretroviral therapy (HAART). METHODS: Ninety-six HIV-infected children were enrolled in the study. Their mean age was 9.7+/-2.6 years, 47% were boys, and 47% were in Centers for Disease Control and Prevention (CDC) clinical category C. All participants had been treated with HAART until they achieved a CD4 cell percentage > or =15%. Three children with a history of clinical measles infection were not included in the data analysis. RESULTS: Only 39 out of 93 children (42%) had a measles-protective antibody level, defined as an anti-measles immunoglobulin G (IgG) level > or =320 mIU/mL. There was no significant difference between the groups with and without protective levels of measles antibody in gender, clinical category, age at which HAART was started, duration of severe immune suppression, CD4 cell count and percentage, or plasma HIV RNA level before and after HAART. CONCLUSIONS: We conclude that, despite a history of measles immunization and evidence of immune reconstitution after HAART, many healthy HIV-infected children are still susceptible to measles.

Epidemiology of invasive meningococcal disease in 13 government hospitals in Thailand, 1994-1999.

This study was conducted to elucidate the magnitude of problem and the clinical course of invasive meningococcal infection from 13 government hospitals in Thailand between 1994 and 1999. Thirty-six strains of Neisseria meningitidis were isolated from 16 blood and 24 cerebrospinal fluid specimens; 4 patients had positive culture in both blood and CSF. Of the 16 strains, 9 (56.3%) were serogroup B. Seventy-one and eighty-four percent of the isolates were susceptible to penicillin and cefotaxime/ceftriaxone respectively. Five out of six penicillin-nonsusceptible strains were found to be relatively resistant to penicillin with the MIC of 0.125 microg/ml. Of 33 patients whose medical records were available, 21 were males and 12 were females, with a mean age of 11.2 years. Fifteen patients (45.5%) presented with meningococcemia and 18 patients (54.5%) presented with meningococcal meningitis. Hypotension and purpura were found in 24.2% and 33.3% of patients respectively. The overall mortality rate was 9.1%. In conclusion, meningococcal disease is not common in Thailand, meningococcemia is a life-threatening condition whereas meningococcal meningitis is much less severe. The prevalence of meningococci relatively resistant to penicillin seems to be increasing.