Pharmacokinetic analyses

Background

Drug concentrations may be affected by aging and this is clinically relevant for life-long treatment like antiretroviral therapy.  One of the major objectives of POPPY is to evaluate associations between antiretroviral drug concentrations and age, and to assess the potential impact of age on drug efficacy, drug-drug interactions and co-morbidities. 

Study aims

Two sets of pharmacokinetic analyses are currently ongoing within POPPY.  The first [link to BHIVA Research Award details] aims to undertake an analysis of the pharmacokinetic parameters of the most commonly used plasma NRTIs in PLWH aged >50 and the younger group of PLWH in order to investigate whether there is a clear correlation between age, drug exposure and toxicity.  The second will measure third agent (PI or NNRTI) drug concentrations and will investigate associations of these with age, drug efficacy, co-morbidities and other factors.

Work to date

Laboratory work has been completed on the baseline samples for NRTI concentration assays and is ongoing for 3rd agent concentration assays. Pharmacokinetic modelling has already begun on the 3rd agent concentration assays, and is expected to be completed in the next two months.

Next steps

Our first analyses will describe the association of markers of renal disease (eGFR) with the PK parameters of the four most commonly used NRTIs in the cohort: tenofovir (TDF), abacavir (ABC), lamivudine (3TC) and emtricitabine (FTC).  These analyses will adjust for age, gender, ethnicity and the use of other concomitant medications that are known to have the potential to cause drug-drug interactions with the NRTIs.  eGFR will be calculated using each of the three standard equations (CKD-EPI, MDRD and Cockroft-Gault).  Four PK parameters will be considered: clearance, area under the curve, peak concentration and trough concentration.  Once these analyses are completed, we will then investigate associations between the PK parameters and markers of liver disease (ALT, AST and bilirubin, after adjusting for factors that are known to affect the liver.

Study group

Marta Boffito (Chelsea and Westminster Hospital), Xinxhu Wang (Imperial College London), Myra McClure (Imperial College London), Caroline Sabin (UCL), Manolis Bagkeris (UCL), Alan Winston (Imperial College London), Laura Dickinson (University of Liverpool), Saye Khoo (University of Liverpool). Contact Marta Boffito (marta.boffito@nhs.net).

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