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Background:
Therapeutic drug monitoring (TDM) in plasma is proposed as a potentially
useful tool in the clinical management of HIV pts. Several PIs exerted in
vitro inhibitory effects on Candida and Pneumocystis at
concentrations clinically achievable in blood in vivo. Few data are
available on PI concentrations in extra-haematic compartments like saliva,
where OI are detectable. We analyzed coupled saliva and plasma samples to
assess: PI levels achievable in vivo under different HAART regimens,
the potential role of saliva as a non-invasive specimen to measure
compliance and to verify if PI concentrations in the mouth reached those
reported as candidicidal in vitro.
Methods:
After informed consent, clinical examination was performed to exclude pts
with visible oral lesions. Coupled blood and saliva samples were provided.
Sampling time was recorded according to the drug's dosing interval. Aliquots
of saliva pellets were Giemsa-stained to score red blood cells as
contamination index. Samples were analyzed according to a validated HPLC
assay. The limit of quantification for PIs detection was 40 ng/ml.
Results:
100 HIV pts were enrolled and coupled samples examined: 39LPV, 21SQV, 14
IDV, 23NFV, 2 RTV, 1 APV. In all pts declaring adherence to prescribed
regimens, PIs were detected in plasma as total (bound or free) drug. Median
(range) plasma concentrations were: LPV 5.94 (0.2-15.2)mcg/ml, SQV 0.52
(0.08-3.2)mcg/ml; IDV 3.26 (0.2-14.7)mcg/ml; NFV 4.23 (0.9-12.4)mcg/ml.
Median (range) of sampling time were, respectively: LPV 5h (2-11 h), SQV 20h
(12-23 h), IDV 4h (1-11 h), NFV 4 h (3-13 h). PIs were detected in 43/97
saliva samples (33.3% LPV, 24%SQV, 71% IDV, 65% NFV). Median (range) saliva
levels in positive samples were: LPV 0.15 (0.08-1.3)mcg/ml (Ratio sal/plasma=
0.03); SQV 0.22 (0.1-0.6)mcg/ml (R=0.14); IDV 2.6 (0.1-10.6)mcg/ml (R=1.0);
NFV 0.3 (0.06-1.5)mcg/ml (R=0.04). No correlation or predictivity was
detected between plasma and saliva levels. Saliva were higher than plasma
levels in 6 pts receiving IDV.
Conclusions:
Saliva samples, though non- invasively and easily collected, do not appear
adequate for PIs TDM. Saliva levels, except for IDV, were lower than those
assessed in vitro as candidicidal, but higher than those indicated as
partially protective against Pneumocystis |
