[Side effects of antiretroviral treatment for transmission prophylaxis in preterm and near-term infants]. / Unerwünschte Wirkungen der antiretroviralen Prophylaxe der HIV-Transmission bei Frühgeborenen unter 35 Schwangerschaftswochen.

BACKGROUND: The aim of this study was to assess the frequency of side effects of antiretroviral treatment in transmission prophylaxis in preterm and near-term infants with a history of HIV-positive mothers. METHODS: A retrospective single-centre study of all neonates born to HIV-positive mothers between 2001 and 2005 and receiving antiretroviral prophylaxis was performed. Respiratory distress was documented as well as possible side effects from antiretroviral drug treatment, e. g., anaemia, need for transfusion, liver and kidney dysfunction, depression of white blood cell count, feeding problems and nosocomial infections. A comparison was made between a group of preterm infants of less than 35 weeks of gestation with one of near-term neonates of more than 34 weeks. To evaluate the influence of prematurity on the frequency of symptoms, a matched pairs group of 50 preterm infants was established as the control group. RESULTS: Anaemia at birth (24 vs. 27 %), transient signs of liver impairment (24 vs. 16.5 %) or kidney dysfunction (4 vs. 0.8 %) as well as nosocomial infections were not significantly more frequent in the preterm group than in near-term group of HIV-exposed infants. Respiratory distress (56 vs. 13 %), postnatal anaemia (84 vs. 27 %). leucocytopenia (36 vs. 4 %), feeding problems (88 vs. 42 %), and blood transfusion (32 vs. 7 %) were more common in the preterm infants. The frequency of feeding problems remained markedly elevated when preterm HIV-exposed neonates were compared to preterm controls. Respiratory distress in near-term infants was seen in 13 % of the cases and 2.6 % of them had to be ventilated artificially. This was a higher frequency than in babies delivered by elective Caesarean section without maternal HIV history. CONCLUSIONS: Transmission prophylaxis in offspring of HIV-positive mothers may give rise to adverse effects. Their frequency is higher in preterm infants than in near-term infants. However; this may be related to prematurity, and not to the antiretroviral treatment itself.

Need for therapeutic drug monitoring in HIV-1 infected children receiving efavirenz doses according to international guidelines.

BACKGROUND: International guidelines for the treatment of HIV-1 infected children recommend efavirenz plus nucleoside reverse transcriptase inhibitor combination therapy for first line therapy. Until now little is known about the steady state pharmacokinetics of efavirenz in children. METHODS: 11 HIV-1 infected children at the age of 4 to 10 years received efavirenz according to body weight adjusted dose recommendations at 10 -15 mg/kg body weight. All children were non nucleoside reverse transcriptase inhibitor (NNRTI) naive, 5/11 received efavirenz as first line therapy. Efavirenz plasma concentrations were assessed before daily dose and 1, 2, 4, 8, 24 h post-dose after medication by established HPLC. RESULTS: 7 of 11 children exhibited efavirenz plasma concentrations below targeted ranges. Mean (95% CI) minimum concentrations (C subsetmin) was 1293 ng/mL (range: 889 -1697) and maximum concentration (C subsetmax) was 5552 ng/mL (3951 - 7153) and the mean area under the time-concentration curve at steady state (AUCss) was 63608 ng*h/mL (44222 - 82989). The linear regression analysis of bodyweight adjusted efavirenz AUCss showed a close correlation between dose/bodyweight and plasma concentrations (r superset2 = 0.79). Efavirenz doses below 12.5 mg/kg lead to an AUC < 60000 ng*h/mL in 7 of 8 cases. Higher efavirenz doses exhibited an AUC within the recommended therapeutic range of 60000 - 120000 ng*h/mL (n = 3). CONCLUSIONS: The data show insufficient plasma concentrations for some children despite efavirenz dosing according to recommendations. Antiretroviral therapy needs to be carefully adjusted in children. Therapeutic drug monitoring is strongly recommended to meet efavirenz plasma levels within the therapeutic range.

Effect of first line therapy including efavirenz and two nucleoside reverse transcriptase inhibitors in HIV-infected children.

OBJECTIVE: In an intent-to-treat study, reduction of viral load, increase in CD4 cell count, clinical benefit and adverse reactions were examined in HIV-infected children receiving first line therapy including efavirenz. METHODS: The data of 10 perinatally infected children (median age: 5.8 years) were evaluated during a treatment period of 24 months. Viral load and CD4 cell count were measured every 4 - 8 weeks. Pharmacokinetic evaluations of efavirenz were performed in all patients at study onset. Adverse reactions were reported after obtaining interval history and examination. RESULTS: At base line, median CD4 cell count was 378 cells/microl (21%) and median viral load was 350,000 copies/ml (5.5 log10 copies/ml). After 24 months of treatment, the median viral load reduction was > 3.5 log10 copies/ ml and HIV-1 RNA < 50 copies/ml was found in 8/10 children (80%). Median CD4 cell count increased to 721 cells/microl (24%) after 3 months and was maintained at a level of >1000 cells/microl (> 25%) after 24 months of treatment. Regarding efavirenz levels, C min. values ranged from 845 to 3550 ng/ml (median: 1845 ng/ml) and C max. values from 2380 to 24 200 ng/ ml (median: 3670 ng/ml). The most common adverse effect was a mild skin rash (4/10 children). CNS symptoms were recorded in one patient and no hyperlipidaemia was seen. CONCLUSION: First line therapy with efavirenz and two NRTIs was well tolerated by HIV-1 infected children and the reduction of viral load seems to be similar to single protease inhibitor-containing regimens.