Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors.

BACKGROUND: Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. METHODS: A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). RESULTS: Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (ß = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (ß = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). CONCLUSIONS: Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

The clinical features, risk of prolonged hospitalization and household infections of hospitalized children for pandemic 2009 influenza A (H1N1) virus infection in Thailand.

OBJECTIVE: To evaluate the clinical features, risk of prolonged hospitalization, and household infection in Thai children hospitalized with 2009 pandemic influenza A/H1N1 virus (pH1N1). MATERIAL AND METHOD: The authors conducted a retrospective chart review of children hospitalized in four Thai tertiary care hospitals between June 1 and September 30, 2009, with reverse-transcriptase-polymerase-chain-reaction confirmed pH1N1. Household contact data were obtained by telephone. RESULTS: Pediatric admissions numbered 115, 58 were females (50.4%). Median age was 5.2 (range 0.5 to 15) years. Fifty-one (44.4%) children had underlying diseases, most commonly asthma 17 (14.8%). Median preadmission illness duration was two days (range 1 to 10). Sixty-one (53.0%) children had lymphopenia. Chest X-ray infiltration was detected in 89 (77.4%) children. Oseltamivir was prescribed in 104 (90.4%) children; 47(45.2%) within 48 hours of illness. 70 (60.9%) children received antibiotics. The median hospitalization was three days (range 1 to 94). Independent (multivariate analysis) factors associated with prolonged hospitalization (> or = 7 days) were aged five to nine years (OR 7.4; 95% CI 1.1-48.9, p = 0.037) and having an underlying disease (OR 5.9; 95% CI 1.5-23.3, p = 0.01). Five (4.3%) children required mechanical ventilation; two (1.7%) children died. Household data showed that 63 of 109 (57.8%) patients had contact with a suspected or confirmed pH1N1 case. There were 39 (15.7%) of 249 household contacts who were probable secondary cases: 23 suspected and 16 confirmed pH1N1 of whom 25 (64.1%) were aged < or = 18 years. CONCLUSION: Most pH1N1 infected hospitalized children had pneumonia, an uneventful short hospitalization, and a low in hospital mortality. Half of the patients were household acquired. Secondary household cases affected mostly children.

Metabolic Disorders in HIV-Infected Adolescents Receiving Protease Inhibitors.

Protease inhibitor (PI) may cause abnormal glucose metabolism, abnormal lipid metabolism, and metabolic syndrome in HIV-infected adults but less well studied in Asian adolescents. This cross-sectional study evaluated anthropometric factors, oral glucose tolerance test, and lipid profiles of perinatally HIV-infected Thai adolescents who had received PI-based antiretroviral therapy for at least 6 months. Eighty adolescents were enrolled [median (IQR) age 16.7 (14.6-18.0) years, 42 males]. Metabolic syndrome, prediabetes, and type 2 diabetes mellitus (T2DM) were found in 8 (10%), 17 (22.1%), and 3 (3.8%) adolescents, respectively. Dyslipidemia was found in 56 (70%) adolescents, with hypertriglyceridemia being the most common type. In multivariate analysis, presence of lipohypertrophy (OR: 25.7, 95% CI: 3.2-202.8; p = 0.002) and longer duration of PI use (OR: 1.04, 95% CI: 1.00-1.08; p = 0.023) were associated with metabolic syndrome. Obesity (OR: 7.71, 95% CI: 1.36-43.7; p = 0.021), presence of lipohypertrophy (OR: 62.9, 95% CI: 4.97-795.6; p = 0.001), and exposure to stavudine for ≥6 months (OR: 8.18, 95% CI: 1.37-48.7; p = 0.021) were associated with prediabetes/T2DM, while exposure to tenofovir for ≥6 months reduced the risk (OR: 0.17, 95% CI: 0.04-0.78; p = 0.022). Metabolic disorders were commonly found in adolescents receiving PI. Careful monitoring and early intervention to modify cardiovascular risk should be systematically implemented in this population particularly those with exposure to stavudine.