Factors associated with tenofovir diphosphate concentrations in dried blood spots in persons living with HIV

J Antimicrob Chemother. 2020 Jun 1;75(6):1591-1598. doi: 10.1093/jac/dkaa070.

Abstract

Objectives: To determine factors associated with interindividual variability in tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBSs) among persons living with HIV (PLWH).

Methods: PLWH who were at least 18 years old and taking tenofovir disoproxil fumarate-containing ART were prospectively recruited and enrolled from a clinical cohort and followed longitudinally (up to three visits over 48 weeks). With log-transformed TFV-DP concentrations in DBSs as the outcome, mixed-model regression analyses were used to assess associations between self-reported 3 month ART adherence, race and other clinical covariates (gender, age, BMI, CD4+ T cell count, estimated glomerular filtration rate, haematocrit, duration on current ART and anchor drug class) on TFV-DP in DBSs.

Results: Five hundred and twenty-seven participants (1150 person-visits) were analysed. Adjusting for race and other clinical covariates, every 10% increase in self-reported 3 month ART adherence was associated with an average TFV-DP concentration increase in DBSs of 28% (95% CI: 24%-32%; P < 0.0001). In the same model, female participants had 20% (95% CI: 3%-40%; P = 0.02) higher TFV-DP concentrations in DBSs, compared with male participants, and every 1 kg/m2 increase in BMI was associated with a decrease in TFV-DP concentration in DBSs by 2% (95% CI: -3% to -1%; P < 0.0001).

Conclusions: Individual patient characteristics were predictive of TFV-DP concentration in DBSs in PLWH receiving tenofovir disoproxil fumarate-based ART. Future research to incorporate these predictors into the interpretation of this ART adherence biomarker, and to establish whether these associations extend to PLWH taking tenofovir alafenamide-containing ART, is needed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenine / analogs & derivatives
  • Adolescent
  • Anti-HIV Agents* / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • Humans
  • Male
  • Organophosphates / therapeutic use
  • Tenofovir / therapeutic use

Substances

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