Evaluation of a practical method to assess antiretroviral adherence in HIV-infected Thai children.

The objective of this study was to evaluate a practical method to assess adherence to antiretroviral therapy by observing virological and immunological responses. We conducted a 12-month longitudinal cohort study of 162 HIV-infected Thai children. Adherence was assessed using 5 methods (self reporting calendar, records of missed doses, pill counts, physician assessment, and an interview questionnaire). CD4 count, percentage and viral load were performed at baseline and at 12 months. Mean adherence rates at 2, 6, and 12 months were 98, 100, and 99% by the calendar method; 98, 100, and 100% by recording missed doses; 96, 96, and 92% by pill count; and 90, 94, and 97% by physician assessment. Poor agreement (kappa < or = 0.1) was found among the methods. There was a statistically significant difference (p = 0.05) in virological response between participants with > or = 95% adherence (0.8 log10) and those with < 95% adherence (0.2 log10) when pill counts were used to assess adherence. In conclusion, despite poor agreement among these tools, a pill count appeared to be the only practical, validated method to differentiate the virological outcome between those who were fully and partially adhere to the treatment regimen.

Recurrent Campylobacter lari bacteremia in X-linked agammaglobulinemia: a case report and review.

X-linked agammaglobulinemia (XLA) is a primary immune deficiency disease with a B-cell defect. We present the first XLA patient who had recurrent Campylobacter lari bacteremia. High dose intravenous immunoglobulin combined with azithromycin once per week, and a complete avoidance of bacterial reservoirs may be helpful for the prevention of C. lari bacteremia.

The first pediatric case of Staphylococcus aureus with heterogenous resistant to vancomycin endocarditis in Thailand.

Staphylococcus aureus with reduced susceptibility to vancomycin has been reports worldwide. Here we report the first pediatric case of heterogeneous vancomycin intermediate resistance Staphylacoccus aureus (hVISA) causing endocarditis in Thailand. A 4 months old girl with truncus arteriosus type IV and ventricular septal defect developed methicillin-resistant S. aureus (MRSA) bacteremia and endocarditis after total repair operation. The patient did not respond to combination antimicrobial treatment including vancomycin. The strain was susceptible to trimethoprim-sulfamethoxazole and vancomycin by conventional antimicrobial susceptibily test. The vancomycin minimal inhibitory concentration by E-test was 2 microg/ml. The strain was judged to be possible heteroresistant when screening was done by one-point population analysis. The subsequent population analysis and testing for the emergence of mutants with reduced susceptible to vancomycin confirmed that this strain was hVISA. Despite the treatment with vancomycin, amikacin, rifampicin and cotrimoxazole, the patient died. hVISA should be suspected in MRSA infections that were refractory to vancomycin therapy could be due to. The emergence hVISA underscored the importance of the prudent use of antibiotics, the laboratory capacity to identify MRSA and hVISA and proper communication with treating clinicians, and the meticulous infection-control measures to prevent transmission.

Initiation of antiretroviral treatment with dual nucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected infants with less advanced disease in a resource-limited setting: a multi-center study in Thailand 1998-2000.

OBJECTIVES: To evaluate the feasibility, duration of efficacy, and outcome of therapy with dual nucleoside reverse transcriptase inhibitors (NTRI) initiated in HIV-infected infants with mild to moderate disease. MATERIAL AND METHOD: During 1998-2000, a multi-center prospective open-labeled operational study was conducted. Antiretroviral naôve HIV-infected infants were enrolled in seven hospitals to receive either zidovudine (AZT) plus lamivudine (3TC) or AZT plus didanosine (ddI). Infants who were in CDC stage "C3" were excluded from the study. RESULTS: Of the 88 infants, the mean age of treatment initiation was 6.8 months, and the mean initial CD4 was 1538 cells/mm3 (21.4%). The z-scores for weight and height increased after 4-8 months of treatment, and by the 24th month, were +0.89 and +0.69 higher than at enrollment. The CD4% peak increased at 8 months of treatment, by a mean increment of 4.19%, but decreased to the level of 1.08% above baseline by the 24th month of treatment. Three (3.4%) infants died, 11 (12%) had disease progression, 7 (8%) was prematurely discontinued from the study protocol due to poor compliance, and 37 (42%) were lost to follow-up. At the end of 24 months, all remaining 30 children were in stable condition with a chance of clinical and immunological stability of 34% and 68% by intention-to-treat and on-treatment analysis, respectively. CONCLUSION: Clinical and immunological benefit from dual NRTI was limited. Treatment of HIV-infected infant with mild to moderate disease in a resource-limited setting may have limited feasibility due to the high drop-out rate.

Effect of antiretroviral therapy in human immunodeficiency virus-infected children.

BACKGROUND: The appropriate timing of antiretroviral (ARV) therapy initiation in children with human immunodeficiency virus (HIV) infection has been uncertain. There was evidence of poorer outcome in adults who initiated treatment at lower baseline CD4 cell count. However, early initiation may not be possible in resource-limited setting and would increased risk of long term side effects and non-adherence. OBJECTIVE: To elucidate the outcome of HIV-infected children who ARV treatment was initiated at different disease stages. MATERIAL AND METHOD: Data from medical records of HIV-infected children who had been followed at Infectious Disease Division, Department of Pediatric Siriraj Hospital were retrospectively reviewed. Clinical response and outcome data were analyzed. RESULTS: From September 1996 to March 2004, there were 200 patients with a median age at treatment initiation of 38 (2-175) months. The median duration of follow up period was 26 (1-91) months. The median baseline CD4 cell count was 545 (2-5016) cells/mm3. The median baseline CD4 percentage was 14.25 (0.11-60). Monotherapy or dual nucleoside reverse transcriptase inhibitor (NRTI) regimens were initiated in 134 (67%), and HAARTwas initiated in 66 (33%) patients. The survival rate in patients who initiated with HAART tended to be better than those initiated with dual NRTI regimens but salvaged appropriately (p=0.2377). The survival rate in those initiated treatment at baseline CD4 > or = 15% was better than those initiated at baseline CD4 < 15% (p=0.0471). CONCLUSION: Initiation of ARV treatment at CD4 more than 15% resulted in a better survival rate than at CD4 below 15%. Initiation with HAART regimen tended to improve survival and resulted in higher CD4 gain especially in cases with baseline CD4< 15%.

Diagnosis disclosure in HIV-infected Thai children.

BACKGROUND: Increasing number of children with perinatally acquired HIV-infection are now surviving into school age and adolescence. Disclosure of diagnosis to these children has become an important clinical issue. Clinical reports and studies from other countries suggest that a significant number of these children have not been told of their HIV status. The objective of this study was to assess diagnosis disclosure status of perinatally acquired HIV-infected Thai children. MATERIAL AND METHOD: Primary caregivers of 96 HIV-infected children aged 5 years and older were interviewed to assess the child disclosure status and the caregivers reasons to disclose or not to disclose the diagnosis to the child. The disclosed children were also interviewed to assess perception of their illness. RESULTS: Nineteen of 96 children (19.8%) had been told of their HIV diagnosis by their caregivers. The mean age of the disclosed children was 9.6 years. Eighty-four percent of the disclosed children reported perception of their illness as having HIV infection or AIDS. Common reasons for non-disclosing were concerns that the child was too young, that the child might be psychologically harmed, and that the child could not keep the secret. Of 77 non-disclosing caregivers, 54 reported that they plan to disclose HIV status to the children in the future. CONCLUSION: This study demonstrates that diagnosis disclosure was made in only 1/5 of HIV-infected children, and that most of the caregivers were reluctant in disclosing serostatus to the child. Development of an appropriate guideline for assisting the caregivers and the children to deal with the difficult disclosure process is needed.

Dyslipidemia and lipodystrophy in HIV-infected Thai children on highly active antiretroviral therapy (HAART).

BACKGROUND: Previous cross sectional studies revealed that dyslipidemia occurs in 50-70% of children receiving highly active antiretroviral therapy (HAART). However, there is no information in children in developing countries where children may have a different nutritional status. OBJECTIVE: To evaluate the incidence and associated risk factors of dyslipidemia following HAART in HIV-infected Thai children. The occurrence of clinical lipodystrophy among these children was also evaluated. MATERIAL AND METHOD: Twenty-three HIV-infected children who initiated HAART from "Access to Care Program" sponsored by MOPH around October 2001. Non-fasting blood tests for lipid profile were performed at enrollment and every 6 months. Triglyceride level was not analysed due to a non-fasting condition. The assessment of clinical lipodystrophy was done every 1-2 months. RESULTS. As of October 2003, 19 (83%) children experienced dyslipidemia. There were 10, 13, 5, and 8 children who had dyslipidemia at 6, 12, 18, and 24 months of HAART The mean total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL) tended to increase over time while the children were on HAART: There was a correlation of elevated total cholesterol and CD4 percentage gain particularly at 18-24 months of treatment (r = 0.596, p = 0.007). Two children developed peripheral lipoatrophy. There were no dyslipidemia-associated risk factors identified. Most of the children had transient abnormal lipid profile. There were only 3 children that had persistent abnormality throughout the 24 months of HAART CONCLUSION: Dyslipidemia was found from 6-12 months of HAART and were mostly transient over time. Peripheral lipoatrophy were found in 2 children. Further follow-up will elucidate the long-term incidence, the association factors, and clinical consequences.

Diagnosis of dengue infection using various diagnostic tests in the early stage of illness.

In order to elucidate the usefulness of various tests in the early course of dengue infection, in terms of diagnosis and correlation with clinical severity, blood specimens were collected every 48 hours on 3 occasions from patients with clinical suspicion of dengue infection with fever for less than 4 days. Viral isolation was attempted by mosquito inoculation (MI), tissue culture inoculation (TC), and reverse transcriptase polymerase chain reaction (RT-PCR). Antibodies were detected by hemagglutination inhibition test (HI), an in-house-ELISA (IH-ELISA), and an ELISA by MRL diagnostics Clinical data were collected from the time of enrollment to complete recovery. Of the 40 patients enrolled, 31 were diagnosed as dengue infection and confirmed by either serology or viral isolation. Of these, 12 had primary infection and 19 had secondary infection. Dengue fever occurred in 9 cases. Dengue viruses were isolated from 28 out of 31 patients, and dengue hemorrhagic fever was diagnosed in 22 patients. Viral serotypes identified by viral isolation, and RT-PCR were concordant: DEN1 was isolated in 8, DEN2 in 13, DEN3 in 5, and DEN4 in 2 patients. Viral isolation yielded positive results on blood collected before the 5th day of fever. MI was more sensitive than TC. RT-PCR was less sensitive than viral isolation during the early days of fever, but became more sensitive after the 5th day of fever. RT-PCR was able to detect virus up to day 7-8 of fever, even after defervescence, and in the presence of antibody. During the febrile stage, serological diagnosis on blood samples taken 48 hours apart was carried out by HI, IH-ELISA, and MRL-ELISA, facilitating diagnosis in 3 (10%), 21 (67%), and 27 (87%) of patients, respectively. All of the patients with secondary infection were diagnosed by MRL-ELISA before defervescence. By the 8th day of fever, a serological diagnosis aided to diagnose in 9 (29%), 29 (93%), and 31 (100%) of patients by HI, IH-ELISA, and MRL-ELISA, respectively.

Breakthrough neurological manifestation during appropriate antituberculous therapy of miliary tuberculosis.

We report a 20-month-old girl with miliary pulmonary tuberculosis and normal neurological findings. While on treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol for 1 month, she developed weakness of the lower extremities without meningism or altered consciousness. A computerized tomogram revealed tuberculomas and basal arachnoiditis. The cerebrospinal fluid findings were compatible with tuberculous meningitis. She responded well to systemic corticosteroids.

Mycobacterium avium complex in HIV-infected Thai children.

Of the 169 human immunodeficiency virus (HIV)-infected children being cared for at Siriraj Hospital from January 1998 to September 2000, 10 had Mycobacterium avium complex (MAC) infection; seven had disseminated disease and three had MAC pneumonia. Nine children were in the advanced stage of HIV disease at the time of diagnosis with the median CD4 count of 7 cells/mm3 and 127 cells/mm3 and the median age of 65 months and 63 months in disseminated MAC and MAC pneumonia respectively. None of these children had received prior chemoprophylaxis. Common clinical findings included prolonged fever, weight loss, lymphadenopathy, hepatosplenomegaly, diarrhea, anemia and leukopenia. The outcome of MAC infection was poor, with a mortality rate of 60 per cent. In in vitro susceptibility testing, clarithromycin was the least resistant drug. With the incidence rate of 2.15 per 100 person-years, the high rate of antimicrobial resistance, and the poor outcome, primary chemoprophylaxis for MAC infection in conjunction with effective antiretroviral therapy should be considered for Thai children in the advanced stage of HIV infection.

High CD4+ T-cells percentage and/or low viral load are predictors of 1-5 years survival in HIV-1 vertically infected Thai children.

OBJECTIVE: Enrolling pediatric HIV children into the clinical trial of when to initiate antiretroviral therapy is a crucial ethical issue. CD4+ T-cells percentage and/or viral load were able to identify potential cases of survival through 5 years of age. METHOD: HIV infected cohort from 1992 to 1994 from Children's and Siriraj Hospitals were followed from 1 through 5 years of age. The outcome was survival or death. The predictors were CD4 percentage and viral load (without age and clinical status adjustment). RESULT: 16 of 35 (45.71%) of the cohort survived through 5 years of age. The probability of survival increased to almost 100 per cent either with CD4+ T-cells percentage of over 22 or viral load of less than 500,000.