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

BACKGROUNDS: Disseminated 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 PRESENTATION: A 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. CONCLUSIONS: IRIS from P. marneffei in HIV-infected people is rare. Appropriate recognition and properly treatment is important for a good prognosis.

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting.

BACKGROUND: Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. METHODS: A retrospective chart review was conducted at 8 Thai sites of children who switched to PI -based regimens due to failure of NNRTI -based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks. RESULTS: Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002). CONCLUSION: Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.

Successful treatment of a child with vascular pythiosis.

BACKGROUND: Human 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 PRESENTATION: A 10-year-old boy with underlying ß-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. CONCLUSIONS: The 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.

Persistence of measles, mumps, and rubella protective antibodies 3 years after revaccination in HIV-infected children receiving antiretroviral therapy.

Three years after measles, mumps, and rubella revaccination in 38 human immunodeficiency virus-infected children who had achieved immune recovery after antiretroviral therapy, the prevalence of protective antibody levels was 85% for measles, 61% for mumps, and 79% for rubella, compared with 88%, 84%, and 100%, respectively, 1 month after revaccination.

Impact of low-level viraemia on virological failure among Asian children with perinatally acquired HIV on first-line combination antiretroviral treatment: a multicentre, retrospective cohort study.

INTRODUCTION: The clinical relevance of low-level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first-line combination antiretroviral therapy (cART). METHODS: CLHIV aged <18 years, who were on first-line cART for ≥12 months, and had virological suppression (two consecutive plasma viral load [pVL] <50 copies/mL) were included. Those who started treatment with mono/dual antiretroviral therapy, had a history of treatment interruption >14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL < 50 copies/mL. Cox proportional hazards models were performed to assess the association between LLV and VF. RESULTS: From January 2008 to September 2016, 508 CLHIV (55% female) were eligible for the study. At baseline, the median age was 9.6 (IQR: 7.0 to 12.3) years, cART duration was 1.4 (IQR: 1.3 to 1.8) years, 97% of CLHIV were on non-nucleoside reverse transcriptase inhibitor-based regimens, and the median CD4 was 25% (IQR: 20% to 30%). Over a median follow-up time of 6.0 (IQR: 3.1 to 8.9) years from baseline, 86 CLHIV (17%) had ever experienced LLV, of whom 32 (37%) had multiple LLV episodes. Female sex, living in Malaysia (compared to Cambodia), having family members other than biological parents/grandparents as a primary caregiver, and baseline CD4 < 25% increased risk of LLV. Overall, 115 children (23%) developed VF, corresponding to a rate of 4.0 (95%CI: 3.4 to 4.9) per 100 person-years of follow-up (PYFU). VF was greater among children who had ever experienced LLV compared with those who maintained virological suppression throughout the study period (8.9 vs. 3.3 per 100 PYFU; p < 0.001). In multivariable analyses, ever experiencing LLV was associated with increased risk of subsequent VF (adjusted hazard ratio: 3.01; 95%CI: 1.97 to 4.60). CONCLUSIONS: LLV increased the risk of subsequent VF among Asian CLHIV who had previously been suppressed on first-line cART. Adherence interventions and additional targeted pVL monitoring may be warranted among children with LLV to facilitate early detection of VF.

Plasma efavirenz concentrations and the association with CYP2B6-516G >T polymorphism in HIV-infected Thai children.

BACKGROUND: Concerns have been raised about the possibility of subtherapeutic efavirenz (EFV) plasma levels in children with the current dosing guideline. Single nucleotide polymorphisms of the hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene have been associated with high interindividual variations in EFV plasma concentrations. Our objective was to determine the adequacy of EFV dosing and explore the influence of CYP2B6-516G>T polymorphisms on EFV plasma concentrations in Thai HIV-infected children. METHODS: A total of 63 HIV-infected children receiving EFV for > or =4 weeks were assessed. Children received EFV daily doses on the basis of body weight bands. Between 12 to 16 h after EFV intake, a blood sample was drawn to measure the EFV plasma concentration and to determine the CYP2B6-516G>T polymorphism using HPLC and direct gene sequencing, respectively. RESULTS: The median age (range) was 12.3 years (3.1-18.7). The mean (+/-sd) EFV plasma concentration was 3,138 ng/ml (3,313). Eight (13%), 45 (71%) and 10 (16%) children had an EFV concentration <1,000 ng/ml, 1,000-4,000 ng/ml and >4,000 ng/ml, respectively. CYP2B6-516 G/G, G/T and T/T genotypes were found in 48%, 41% and 11% children, respectively. The CYP2B6-516G>T allele frequency was 31.75%. The mean (+/-sd) EFV concentration for children with G/G, G/T and T/T genotypes were 1,604 ng/ml (729), 2,635 ng/ml (1,199) and 11,582 ng/ml (2,972), respectively (P<0.001). A correlation between EFV concentrations >4,000 ng/ml and psychiatric side effects was observed (P=0.02), but there was no association with rash, hepatotoxicity or central nervous system disturbances. CONCLUSIONS: Current EFV dosing guidelines provide adequate plasma drug concentrations in Thai HIV-infected children. CYP2B6-516G>T polymorphisms significantly affect the drug metabolism of EFV in children.

Efficacy of non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy in Thai HIV-infected children aged two years or less.

Twenty-six Thai HIV-infected children, aged 2 years or less were prospectively enrolled to receive non-nucleoside reverse transcription inhibitor-based highly active antiretroviral therapy (HAART). Twenty-two children (85%) had World Health Organization clinical stage 3 or 4. The median baseline CD4 cell percentage and plasma HIV RNA were 17% and 5.9 log 10 copies/mL, respectively. The median age at HAART initiation was 9.8 months (range, 1.5-24.0). One child died. The mean CD4 cell percentages at 24, 48, and 96 weeks of treatment were 26%, 31%, and 37%, respectively. The proportions of children with virologic suppression (<400 copies/mL) at week 24 and 48 were 14/26 (54%) and 19/26 (73%), respectively. Non-nucleoside reverse transcription inhibitor-based HAART is safe and effective in HIV-infected young children in a resource-limited setting.

Pattern and predictors of immunologic recovery in human immunodeficiency virus-infected children receiving non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy.

BACKGROUND: Non-nucleoside reverse transcription inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) is the recommended first-line regimen for children in Thailand. This study was aimed to assess pattern and predictors of immune recovery in antiretroviral-naive Thai children starting NNRTI-based HAART. METHODS: Records were extracted from clinical databases of 2 treatment cohorts in Thailand. The inclusion criteria were HIV-infected naive children who initiated NNRTI-based HAART when CD4 <25%. Immune recovery was defined as achieving a target CD4% of 25. The impact of age, gender, baseline clinical category, CD4 and HIV RNA titer, and regimen on immune recovery to weeks 96 was assessed using multiple logistic regression. RESULTS: There were 274 patients (52% females) with a median baseline age of 7 (Interquartile range [IQR]: 4-9) years and a median CD4% of 5 (IQR: 1-12) who started treatment with nevirapine (66%) or efavirenz (34%) based HAART. Median duration of follow-up was 168 (IQR: 120-192) weeks. The median CD4% increase from baseline was 7% (IQR: 5-11) and 18% (IQR: 12-23) at weeks 24 and 96, respectively. The probability of reaching target CD4% was 51% (95% confidence interval: 45%-57%) by week 96. The predictors of immune recovery at week 96 were younger age, female gender, higher baseline CD4%, and sustained virologic suppression after week 24. CONCLUSION: In this cohort of children with low baseline CD4, half achieved immune recovery after 96 weeks of HAART. The predictors for immune recovery are younger children, female gender, high baseline CD4%, and long-term virologic suppression.

Impact of the frequency of plasma viral load monitoring on treatment outcomes among children with perinatally acquired HIV.

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.

Quality of life among HIV-infected children in Thailand.

The aim of the study was to measure quality of life in human immunodeficiency virus-infected children. This is a cross-sectional study among main caregivers of human immunodeficiency virus-infected children. The questionnaire consisted of 5 main domains: general health, physical functioning, symptoms, psychological well being, and social and role functioning. A total of 131 main caregivers (21% males, average age 42.5 years) of human immunodeficiency virus-infected children (28% male, average age 10.1 years) answered the questionnaires. Four out of 5 domains showed that children without immune suppression had a significantly higher quality of life than children with immune suppression. There was a significant correlation between health care utility and physical functioning, symptoms, and social and role functioning. The instrument had acceptable internal consistency and was a feasible measure of quality of life among human immunodeficiency virus-infected children. The information obtained will enable health care providers to establish comprehensive health care services to serve the needs of these children and their families.

Family Functioning in Adolescents with Perinatal HIV Infection.

This study aimed to assess family functioning in adolescents with perinatal HIV infection receiving antiretroviral therapy compared with healthy controls. Correlations between self-reported and caregiver-reported family functions were also evaluated. A sample of 195 participants including 65 perinatally HIV-infected adolescents and 130 healthy controls were enrolled. The total family functioning score in HIV-infected adolescents was significantly lower than that in healthy controls by self-report (105.86 vs 115.41; P ≤ .001). Caregivers of HIV-infected adolescents also reported lower scores of family functioning than those of controls (109.91 vs 114.98; P ≤ .001). Among the HIV-infected group, there was no or minimal correlation between the self-reported and caregiver-reported total scores of family functioning. However, there were moderate correlations between self-reported and caregiver-reported family functioning total scores in the control group. Overall, HIV-infected adolescents reported lower family functioning than healthy controls. Improved functioning in the family may help with better adjustment in perinatally HIV-infected adolescents.

Response to measles, mumps, and rubella revaccination in HIV-infected children with immune recovery after highly active antiretroviral therapy.

BACKGROUND: The low prevalence of measles antibody in human immunodeficiency virus (HIV)-infected children after immune recovery as a result of highly active antiretroviral therapy increases the risk of morbidity and mortality from disease. The objective of our study was to evaluate the efficacy and safety of revaccination with measles, mumps, and rubella (MMR) vaccine in HIV-infected children with immune recovery. METHODS: Inclusion criteria were (1) HIV-infected children aged >5 years, (2) a nadir CD4 lymphocyte percentage 15% for >or=3 months after highly active antiretroviral therapy), and (4) no protective antibody against measles. Each child received 1 dose of MMR vaccine, and antibodies were measured at 4 and 24 weeks after vaccination. Protective antibodies were defined as an antimeasles immunoglobulin G (IgG) level >or=320 mIU/mL, an antimumps IgG titer >1:500, and an antirubella IgG level >10 IU/mL. RESULTS: There were 51 participants. The mean age (+/- standard deviation) was 10.2 +/- 2.5 years. Prior to revaccination, 28 participants (55%) had baseline protective antibody to mumps, and 11 (20%) had baseline protective antibody to rubella. The prevalence of protective antibody at 4 weeks was 90%, 100%, and 78% for measles, rubella, and mumps, respectively, and then slightly decreased to 80%, 94%, and 61%, respectively, at 24 weeks after revaccination. No serious adverse reactions were attributed to revaccination. CONCLUSIONS: The majority of HIV-infected children with immune recovery can develop protective antibodies after MMR revaccination. Revaccination with MMR vaccine in HIV-infected children with immune recovery should be considered to ensure individual immunity and limit the spread of disease.

Hospitalization and mortality among HIV-infected children after receiving highly active antiretroviral therapy.

BACKGROUND: Pediatric antiretroviral therapy programs have recently been implemented in resource-limited settings. Their impact in a prospective cohort is not well documented. The aim of this study was to evaluate the rates and causes of hospitalization and mortality among human immunodeficiency virus (HIV)-infected Thai children after receiving highly active antiretroviral therapy (HAART). METHODS: Children who started receiving HAART from August 2002 to March 2005 were prospectively observed. The patients included in the study were antiretroviral-naive HIV-infected children who had CD4 cell percentages < or =15% before treatment. All patients were observed for at least 48 weeks. RESULTS: One hundred ninety-two children were included. The mean age at HAART initiation was 7.6 years (range, 0.4-14.8 years). At baseline, the mean CD4 cell percentage (+/-SD) was 5.2%+/-4.9%, and the mean plasma HIV RNA level (+/-SD) was 5.4+/-0.5 log(10) copies/mL. Sixty-seven children (35%) were hospitalized a total of 108 times. The hospitalization rate decreased from 30.7% during the first 24-week period to 2.0% during weeks 120-144 after initiation of HAART. Fifty-nine hospital admissions (54.6%) occurred during the first 24 weeks of HAART. Causes of hospitalization were pneumonia and other bacterial infections (61.7%), immune reconstitution syndrome (23.4%), noninfectious illness (6.5%), opportunistic infection (5.6%), and drug-related events (2.8%). The mortality rate decreased from 5.7% in the first 24 weeks to 0%-0.6% in the subsequent 24-week intervals. CONCLUSION: Hospitalization and mortality rates significantly decreased among HIV-infected children receiving HAART. Most hospitalizations and deaths occurred during the first 24 weeks of HAART.

Lipodystrophy and metabolic changes in HIV-infected children on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) has recently been implemented in Thailand. Its long-term effects have not been clearly evaluated. The objective of this study was to estimate the prevalence of lipodystrophy (LD) and other metabolic changes in HIV-infected children receiving HAART. METHODS: Ninety children who began HAART (either nevirapine or efavirenz, together with lamivudine and stavudine) were prospectively followed. LD was assessed by waist-to-hip ratio and LD checklist. Hypercholesterolaemia was defined as total cholesterol > 200 mg/dl and low-density lipoprotein cholesterol > 130 mg/dl. Low levels of high-density lipoprotein cholesterol (HDL-c), hypertriglyceridaemia and hyperglycaemia were defined as HDL-c < 40 mg/dl, triglyceride > 200 mg/dl and plasma glucose > 110 mg/dl, respectively. RESULTS: The mean age at entry was 7.6 (SD 2.9) years. Fifty-three children received nevirapine- and 37 received efavirenz-based HAART. The prevalence of LD was 9%, 47% and 65% at 48, 96 and 144 weeks after HAART initiation, respectively. Patterns of LD at week 144 were central lipohypertrophy (46%), peripheral lipoatrophy (20%), and combined type (34%). A higher prevalence of LD was found among females (61% versus 39%; P = 0.04) and those with more advanced disease (CDC category B or C) at baseline (73% versus 51%; P = 0.04). There was no difference in prevalence of LD between the two regimens. At 144 weeks, fasting hypertriglyceridaemia was detected in 12%, hypercholesterolaemia in 11%, and increased plasma glucose in 4% of children. Low HDL-cholesterolaemia decreased from 94% at baseline to 12% at week 144 (P < 0.01). CONCLUSIONS: More than half of the children developed LD at 144 weeks after HAART. Dyslipidaemia occurred in 11-12% of children.

Sustained immunologic and virologic efficacy after four years of highly active antiretroviral therapy in human immunodeficiency virus infected children in Thailand.

We report the long-term efficacy of highly active antiretroviral therapy (HAART) in 107 antiretroviral-naive human immunodeficiency virus (HIV)-infected Thai children. In an intention-to-treat analysis, 70% of the children had undetectable HIV RNA titers after 192 weeks of HAART. The mean CD4 cell percentage increased from 5.3% to 26.6%. HAART is effective for HIV-infected children in this resource-poor setting despite initiation of treatment in the advanced stage of disease.

Immune reconstitution syndrome after highly active antiretroviral therapy in human immunodeficiency virus-infected thai children.

BACKGROUND: There is little information about the immune reconstitution syndrome (IRS) in children, especially from resource-poor countries. OBJECTIVE: To determine the incidence and spectrum of IRS in advanced stage human immunodeficiency virus (HIV)-infected children after initiation of highly active antiretroviral therapy (HAART). METHODS: Between May 2002 and April 2004, 153 symptomatic HIV-infected children who had CD4 lymphocyte percentage < or =15% initiated HAART in a national antiretroviral drug access program. All patients were followed for 48 weeks. In this study, IRS was defined as a disease event caused by microorganisms or conditions previously reported to be associated with IRS in patients having immunologic and/or virologic response to HAART. RESULTS: The incidence of IRS was 19% (95% confidence interval, 13.1-26.1). The median time of onset was 4 weeks after start of HAART (range, 2-31). There were 32 episodes of IRS, including 14 caused by mycobacterial organisms, 7 by varicella-zoster virus, 7 by herpes simplex virus, 3 by Cryptococcus neoformans and 1 episode of Guillain-Barré syndrome. Patients who had IRS develop had lower baseline CD4 lymphocyte percentages compared with those who did not (P = 0.02). CONCLUSIONS: IRS is common among HIV-infected children who received HAART in their advanced stage of disease. Educational programs for patients and health care workers on recognizing and treating these conditions should be integrated into antiretroviral treatment access programs.

Immune reconstitution syndrome from nontuberculous mycobacterial infection after initiation of antiretroviral therapy in children with HIV infection.

The immune reconstitution syndrome caused by nontuberculous mycobacterial (NTM) infection is reported in 9 of 153 HIV-infected children 2 to 26 weeks after initiation of antiretroviral therapy. The clinical syndrome included fever and dyspnea (2 children), fever and abdominal pain (3), subcutaneous nodules or suppurative lymphadenitis (4). The causative species were Mycobacterium avium (4), Mycobacterium scrofulaceum (3), Mycobacterium kansasii (1) and Mycobacterium simiae (1).

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

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.

The 10-year effectiveness of combination antiretroviral treatment in perinatally HIV-infected children participating in Thailand's National Access Program.

BACKGROUND: The National Access to Antiretroviral Program for People Living with HIV/AIDS was launched in Thailand in 2002. HIV-infected, antiretroviral-naive, severely immunosuppressed children were initiated on highly active combination antiretroviral treatment (cART). This study aimed to determine the long-term effectiveness of cART. METHODS: Data were extracted from medical records. Primary end points were mortality rate, proportion of children who remained on first-line cART regimen and children with plasma HIV RNA level (pVL) <50 copies/ml at week 520. RESULTS: From August 2002 to July 2003, 107 children were enrolled. The baseline median age was 7.6 years (IQR 5.7-10.0), the median CD4(+) T-cell count was 60 cells/mm(3) (IQR 21-272) and the median pVL was 5.37 log10 copies/ml (IQR 5.01-5.76). The mortality rate during and after the first year was 3.7 and 0.006 deaths/100 person-years, respectively. At week 520, 90 (84%) continued to be actively followed. Their median age was 17.8 years (IQR 15.8-19.8). 73 (81% as-treated) remained on the first-line regimen, while 18 (20%) had switched to a second-line cART regimen, at the median time of 272 weeks (IQR 256-363) after the first-line cART initiation. 69 (77%) had pVL<50 copies/ml and the median CD4(+) T-cell count was 636 cells/mm(3) (IQR 466-804). 83 (92%) and 64 (71%) had CD4(+) T-cell counts ≥200 and >500 cells/mm(3), respectively. CONCLUSIONS: Long-term virological control, favourable immunological outcomes and healthy survival was achieved in severely immunosuppressed, perinatally HIV-infected children who started first-line NNRTI-based cART. Continuing surveillance for long-term complications is warranted.

Immune reconstitution syndrome due to bacillus Calmette-Guérin after initiation of antiretroviral therapy in children with HIV infection.

The immune reconstitution syndrome caused by bacillus Calmette-Guerin (BCG) was found in 4 HIV-infected children who were immunized with BCG at birth. The localized, suppurative, BCG-related complications developed within 10 weeks after initiation of antiretroviral therapy. The incidence rate was 2.7 cases per 100 persons (95% confidence interval, 0.7-6.7). Patients responded well to treatment with isoniazid and rifampicin.