Once- versus twice-daily lopinavir/ritonavir tablets in virologically suppressed, HIV-infected, treatment-experienced children: comparative pharmacokinetics and virological outcome after switching to once-daily lopinavir/ritonavir.

OBJECTIVES: Data on lopinavir/ritonavir tablets administered once daily in children are limited. We compared the pharmacokinetics (PK) of lopinavir/ritonavir twice daily versus once daily in virologically suppressed, HIV-infected children, and assessed the virological outcome, at 48 weeks, in children receiving the regimen of lopinavir/ritonavir once daily. PATIENTS AND METHODS: HIV-infected children receiving a twice-daily lopinavir/ritonavir-based regimen and with an HIV-1 RNA viral load (VL) <40 copies/mL for at least 3 months were enrolled. Intensive steady-state 12 h blood sampling for PK assessment was performed at enrolment. Immediately afterwards, the lopinavir/ritonavir dose was changed to once daily with the equivalent daily dose, and intensive steady-state 24 h blood sampling was repeated 2 weeks later. If the lopinavir C(trough) was <1.0 µg/mL, the lopinavir/ritonavir dose was increased by 20%-30% and C(trough) measurement repeated. CD4 cell counts and VL were determined at baseline and at 12, 24 and 48 weeks. RESULTS: Twelve children were enrolled. The median age was 13.1 years. Lopinavir AUC(0-24) following twice-daily and once-daily dosing was 169.7 (124.0-200.8) and 167.1 (95.1-228.1) µg · h/mL, respectively. Seven children, including all six concomitantly receiving efavirenz, had a C(trough) <1.0 µg/mL with once-daily lopinavir/ritonavir dosing, and four of seven children had a C(trough) <1.0 µg/mL after dose adjustment. All children maintained virological suppression throughout the 48 week period. CONCLUSIONS: Lopinavir/ritonavir-based once-daily regimens could simplify therapy in children/adolescents with virological control, but a lower lopinavir C(trough) was evident. Further efficacy studies of lopinavir/ritonavir once daily in children are necessary before routinely recommending this dosing strategy.

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.