Evaluation of Saliva as an Alternative Matrix for Monitoring Plasma Zidovudine, Lamivudine and Nevirapine Concentrations in Rwanda

Abstract

Saliva may provide interesting advantages as matrix for compliance measurements, pharmacokinetic studies and therapeutic drug monitoring in resource limited countries. We investigated the feasibility of using saliva for compliance monitoring of zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP) in 29 HIV-1 infected patients from Rwanda. ZDV, 3TC and NVP drug levels were quantified by an LC/MS-MS method in plasma and stimulated saliva samples and compared using Bland-Altman analysis. Seven patients demonstrated undetectable saliva ZDV levels while five out of these seven also showed no 3TC salivary concentrations. For the other samples, we observed a good agreement between salivary and plasma concentrations of each antiretroviral drug. A significant relation between the difference in saliva and plasma ZDV concentrations and the average ZDV concentration in the two matrices was deduced as follows: y = -380.15 + 1.79 x. The log saliva and plasma concentration difference of both 3TC and NVP was consistent across the range of average log concentration. Overall, we showed large agreement limits suggesting a wide inter patient variability that may result in non-reliable plasma level predictions from saliva drug measurements. Therefore, our results indicate that saliva may serve as a valuable tool only for NVP compliance testing because of its high salivary concentration.

Antiretroviral Concentration in Hair as a Measure for Antiretroviral Medication Adherence: A Systematic Review of Global Literature

“…Second, there was limited research examining the associations between HAC and some new non-PK or PK adherence measures in this field. These new non-PK (e.g., short message service, or SMS [55] ) and PK measures (e.g., ARV concentration in saliva [56,57] or urine [58,59] ) have shown potential advantages in improving accuracy of the ARV medication adherence measures in HIV-related research. The associations between HAC and new non-PK or PK adherence measures may provide additional insight on the validity of HAC as a measure of long-term ARV medication adherence.…”

“…Simultaneous determination of multiple ARV drugs in hair is also technically possible [12,13,19,20] . On the other hand, additional ARV medication adherence measures are available in adherence research , such as SMS, pharmacy refill records, ARV concentration in saliva [56,57] and urine [58,59] , and CD4 lymphocyte count. The associations of available HAC with additional ARV medication adherence measures and PD responses might provide more information regarding the utility and validity of HAC as an objective measure for long-term ARV medication adherence.…”

Hyphenated mass spectrometry techniques for assessing medication adherence: advantages, challenges, clinical applications and future perspectives

“…It is only through the increased sophistication and detection capabilities of MS instruments that the microvolume DBS and VAMS sample can provide comparable data to a 1 mL blood sample. This enhanced analytical capability has also spurned the investigation of alternate less invasive biosample matrices including hair and saliva for assessing medication adherence [10,11,58,63,65,66,68,70,73,78,84,86,118,[129][130][131]. The choice of the most appropriate biosample would depend on a number of factors including the ease of sample collection from the patient and knowing if the available biosample size contains sufficient target analyte to be detected.…”

“…There is also the challenge with carrying out venous sampling in certain populations like paediatric patients. To address these issues, other more patientfriendly sampling methods such as saliva, hair and DBS have been investigated for ART therapy adherence assessment [10,58,60,63,65,66,68,70,[73][74][75].…”

Continuous, Quantitative Monitoring of Roxithromycin in Human Saliva by Flow Injection Chemiluminescence Analysis

“…Human saliva, in which the concentrations of many clinically relevant analytes and drugs generally reflect the levels in tissue fluid or plasma, 1,–3 is becoming a welcome and well accepted, biological matrix in diagnostic research 4,–6 and clinical chemistry. 7,–9 The human saliva matrix of a promising, bioavailable specimen has been used in different scientific fields, without the need for specialized equipment or personnel, and as a disease marker for oral and lung cancers, 10,–12 diabetes, 13,14 malaria, 15 and renal disease 16 ; in drug testing for benzodiazepine, 17 amphatamine, 18 and diazinon 19 ; in pharmacokinetic studies of Δ9-tetrahydrocannabinol 20 and mycophenolic acid 21 ; and in therapeutic drug monitoring for voriconazole, 22 haloperidol, 23 and mefloquine, 24 among others. To date, there has been little comprehensive data available from quantitative monitoring of roxithromycin (ROX) in human saliva after oral intake.…”