Moderately High Tenofovir Diphosphate in Dried Blood Spots Indicates Drug Resistance in Viremic Persons Living with HIV

J Int Assoc Provid AIDS Care. 2019 Jan-Dec:18:2325958219888457. doi: 10.1177/2325958219888457.

Abstract

Background: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a strong predictor of viral suppression in persons living with HIV (PLWH). Its association with antiretroviral therapy (ART) resistance remains unknown.

Methods: Blood was collected in PLWH receiving TDF-containing ART enrolled in a 48-week study. Tenofovir diphosphate/emtricitabine triphosphate (FTC-TP) were quantified from the same sample as HIV viral load (VL) in PLWH who developed resistance within ≤12 months.

Results: The study enrolled 807 participants, of whom 10 had new resistance-conferring mutations. Among these, median (interquartile range) TFV-DP and HIV VL were 956 (407-1510) fmol/punch and 9840 (513-68,200) copies/mL, respectively. Five had quantifiable FTC-TP in DBS. Based on previously published data, a TFV-DP concentration of 956 fmol/punch would have an adjusted odds of virologic suppression of 32.8 versus TFV-DP <350 fmol/punch, making viremia of ∼10,000 copies/mL an unexpected outcome.

Conclusion: Moderately high TFV-DP in DBS (700-1249 fmol/punch) in PLWH with high viremia suggest that antiretroviral drug resistance might be present.

Keywords: ART; dried blood spots; drug resistance; emtricitabine triphosphate; tenofovir diphosphate.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / blood
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / blood*
  • Anti-HIV Agents / therapeutic use
  • Dried Blood Spot Testing*
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Organophosphates / blood*
  • Organophosphates / therapeutic use
  • Prospective Studies
  • Sustained Virologic Response
  • Viral Load / drug effects*
  • Viremia / drug therapy*

Substances

  • Anti-HIV Agents
  • Organophosphates
  • tenofovir diphosphate
  • Adenine