Using dried blood spots to facilitate therapeutic drug monitoring of antiretroviral drugs in resource-poor regions

J Antimicrob Chemother. 2018 Oct 1;73(10):2729-2737. doi: 10.1093/jac/dky254.

Abstract

Objectives: We evaluated whether dried blood spots (DBS) are suitable to monitor combined ART when samples are collected in rural Tanzania and transported over a long distance to a specialized bioanalytical laboratory.

Methods: Plasma and DBS samples were collected in Tanzania from study patients treated with nevirapine, efavirenz or lopinavir. In addition, plasma, whole blood and DBS samples were obtained from a cohort of HIV patients at the site of the bioanalytical laboratory in Switzerland. DBS samples were analysed using a fully automated LC-MS/MS method.

Results: Comparison of DBS versus plasma concentrations of samples obtained from the bridging study in Switzerland indicated an acceptable bias only for nevirapine (18.4%), whereas for efavirenz and lopinavir a pronounced difference of -47.4% and -48.1% was found, respectively. Adjusting the DBS concentrations by the haematocrit and the fraction of drug bound to plasma proteins removed this bias [efavirenz +9.4% (-6.9% to +25.7%), lopinavir +2.2% (-20.0% to +24.2%)]. Storage and transportation of samples from Tanzania to Switzerland did not affect the good agreement between plasma and DBS for nevirapine [-2.9% (-34.7% to +29.0%)] and efavirenz [-9.6% (-42.9% to +23.8%)]. For lopinavir, however, adjusted DBS concentrations remained considerably below [-32.8% (-70.4% to +4.8%)] corresponding plasma concentrations due to decay of lopinavir in DBS obtained under field conditions.

Conclusions: Our field study shows that the DBS technique is a suitable tool for therapeutic drug monitoring in resource-poor regions; however, sample stability remains an issue for certain analytes and therefore needs special consideration.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alkynes
  • Anti-Retroviral Agents / blood*
  • Anti-Retroviral Agents / therapeutic use*
  • Benzoxazines / blood
  • Benzoxazines / therapeutic use
  • Biological Transport
  • Cohort Studies
  • Cyclopropanes
  • Dried Blood Spot Testing / economics
  • Dried Blood Spot Testing / methods*
  • Drug Monitoring / economics
  • Drug Monitoring / methods*
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Health Resources*
  • Humans
  • Lopinavir / blood
  • Lopinavir / therapeutic use
  • Male
  • Middle Aged
  • Nevirapine / blood
  • Nevirapine / therapeutic use
  • Rural Population
  • Switzerland
  • Tanzania

Substances

  • Alkynes
  • Anti-Retroviral Agents
  • Benzoxazines
  • Cyclopropanes
  • Lopinavir
  • Nevirapine
  • efavirenz