Article Text

  1. N. Rakhmaninaa,
  2. J. van den Ankera,
  3. H. Spiegela,
  4. J. Severa,
  5. S. Soldina
  1. abDivisions of Pediatric Clinical Pharmacology, cInfectious Diseases and dDepartment of Laboratory Medicine


Introduction Therapeutic drug monitoring (TDM) of nevirapine (NVP) in HIV-infected children has gained importance since the introduction of NVP in perinatal regimens for the prevention of mother-to-child HIV transmission. Adequate trough serum levels of NVP predict successful therapy whereas subtherapeutic levels are correlated with higher viral loads. However, obtaining NVP levels in children is painful, requires additional blood losses, access to sterile equipment and higher cost in collection. Therefore, less invasive methods for TDM in pediatric patients with HIV are needed. Our previous studies did suggest that saliva might be used as a non-invasive method for TDM of several antiretroviral drugs.

Purpose To determine the total and free levels of NVP in plasma in HIV-infected children and compare them with saliva concentrations.

Methods 20 pediatric African-American patients (9 boys, 11 girls) aged 4-21 years (median age of 8.2 years) receiving highly active antiretroviral therapy with NVP were studied. The median time from NVP intake to trough level measurement was 5.6 hours. Unbound NVP was separated by ultrafiltration using the Amicon Centrifree micropartition system and NVP plasma and saliva levels were determined by a tandem-mass spectrometry using the Applied Biosystems/Sciex API-2000. Within-run precision was below 7% and between-day precision was below 10% for all NVP at the tested concentrations. Accuracy ranged between 95% and 105%. Linear regression analysis was performed through PRISM program.

Results The correlation of saliva to total and free plasma concentrations of NVP was highly significant with r values of 0.971 (NVPSal = 0.587 × NVPtotalPl + 444.5, p<0.001) and 0.969 (NVPSal = 1.23 × NVPfreePl + 584.0, p<0.001). Total and free plasma levels of NVP also showed a significant correlation with an r value of 0.949 (NVPfreePL = 0.419 × NVPtotalPL + 144.2, p<0.001).

Conclusion This study shows a significant linear correlation between total saliva and both bound and unbound (free) plasma levels of NVP. The levels of NVP in saliva correlate significantly with plasma values and may be useful for non-invasive TDM of NVP therapy.

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