CNS penetration of ART in HIV-infected children.

Autor: den Hof, Malon Van, Blokhuis, Charlotte, Cohen, Sophie, Scherpbier, Henriette J., Pajkrt, Dasja, Van den Hof, Malon, Wit, Ferdinand W. N. M., Pistorius, M. C. M., Mathot, Ron A. A., Kootstra, Neeltje A., Teunissen, Charlotte E.
Předmět:
Zdroj: Journal of Antimicrobial Chemotherapy (JAC); Feb2018, Vol. 73 Issue 2, p484-489, 6p
Abstrakt: Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce.Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function.Patients and methods: Antiretroviral drug levels were measured in paired CSF and blood samples of clinically stable HIV-infected children between 8 and 18 years old on long-term combined ART. Plasma drug concentrations were corrected for protein binding. We evaluated CNS penetration using CSF/plasma ratios and compared CSF concentrations with the IC50 as a surrogate marker for effectiveness. Blood-brain barrier permeability was assessed for possible confounding. Associations with neurocognitive function were explored using linear regression analysis.Results: Median CSF/plasma ratios (IQR) were: lopinavir 0.059 (0.024-0.157, n = 7), efavirenz 0.681 (0.555-0.819, n = 12), tenofovir 0.021 (0.020-0.024, n = 4), lamivudine 0.464 (0.331-0.607, n = 17), emtricitabine 0.365 (0.343-0.435, n = 3), nevirapine 1.203 (n = 1), zidovudine 0.718 (0.711-1.227, n = 5) and abacavir 1.344 (0.670-2.450, n = 10). CSF concentrations were below the IC50 for tenofovir (100%), emtricitabine (100%), abacavir (50%) and zidovudine (17%). Lamivudine, lopinavir, efavirenz and nevirapine concentrations were all above the IC50. All participants were virologically suppressed in blood and CSF. CSF drug concentrations were not associated with blood-brain barrier permeability or neurocognitive function.Conclusions: We showed adequate CSF concentrations of lamivudine, lopinavir, efavirenz and nevirapine, and potential suboptimal CSF concentrations of tenofovir, abacavir and emtricitabine in long-term treated HIV-infected children. None the less, the use of combined antiretroviral drugs led to adequate viral suppression. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index