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Background: We assessed cumulative antiretroviral exposure-using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS)-in persons with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) as single-tablet regimens (STR) or multiple-tablet regimens (MTR)., Methods: Blood for DBS was prospectively collected in PWH on TDF during 1144 person visits (n = 523). Linear mixed-effects models, adjusted for baseline characteristics, were used to compare TFV-DP in STR versus MTR. Models adjusted for ART regimen using either anchor drug class, pharmacokinetic booster status (unboosted [u/] or boosted [b/]), or a combined STR/MTR and booster categorical variable., Results: In the anchor class-adjusted model, STR had 19% (95% confidence interval [CI]: 3%-37%; p = 0.02) higher TFV-DP concentrations than MTR. However, in the booster-adjusted model, STR was not significantly higher than MTR (estimate 5%, 95% CI: -9% to 21%; p = 0.48), although PWH on b/ART had 35% (95% CI: 16%-58%; p = 0.0001) higher TFV-DP than u/ART. In the STR/MTR-boosted variable model, when compared to u/MTR, b/STR, b/MTR, and u/STR had 25% (95% CI: 7%-47%; p = 0.005), 37% (95% CI: 17%-59%; p < 0.0001), and 7% (95% CI: -7% to 24%; p = 0.34) higher TFV-DP, respectively. Compared with b/MTR, b/STR had 9% (95% CI: -31% to 10%; p = 0.37) lower TFV-DP. In a sensitivity analysis of PWH with HIV viral load <20 copies/ml at all visits, b/STR and b/MTR had 34% (95% CI: 16%-55%; p < 0.0001) and 12% (95% CI: -2% to 27%; p = 0.09) higher TFV-DP, respectively, compared with u/MTR, while u/STR had 4% (95% CI: -15% to 8%; p = 0.50) lower TFV-DP. Compared with b/MTR, b/STR had 17% (95% CI: 2%-30%; p = 0.03) higher TFV-DP., Conclusions: Persons with HIV on b/TDF-based ART had higher TFV-DP than u/ART, regardless of STR or MTR use. No significant differences in TFV-DP between regimens of the same boosting status (i.e., b/STR vs. b/MTR; u/STR vs. u/MTR) were observed in the full cohort. Future research should examine the clinical utility of these findings in patient-tailored ART selection., (© 2022 Pharmacotherapy Publications, Inc.)

Study Objective: To assess the association between tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), a measure of cumulative tenofovir-based antiretroviral (ART) adherence, with medication regimen complexity in persons with human immunodeficiency virus (PWH)., Design: Prospective clinical cohort (up to three visits over 48 weeks)., Setting: Academic-based HIV clinic., Patients: PWH receiving tenofovir disoproxil fumarate (TDF)-based ART., Measurements: DBS for TFV-DP were collected at every study visit. Baseline patient-level medication regimen complexity index (pMRCI) scores were calculated and categorized into three sub-scores (disease-specific [ART], non-ART, and over-the-counter [OTC]). The pMRCI scores were evaluated to assess the association with TFV-DP in DBS <350 fmol/punch after adjusting for clinical covariates. pMRCI scores were also categorized to estimate the adjusted relative risk (aRR) of having a TFV-DP <350 fmol/punch between pMRCI quartiles., Main Results: Data from 525 participants (1,146 person-visits) were analyzed. Baseline median (interquartile range [IQR]) pMRCI scores for participants with TFV-DP in DBS <350 vs. ≥350 fmol/punch were 4 (3, 8) vs. 4 (2, 6) for ART, 27 (12, 31) vs. 12 (5, 22) for non-ART, and 0 (0, 1) vs. 0 (0, 2) for OTC, respectively. For the non-ART scores, the aRR for having a TFV-DP in DBS <350 fmol/punch was 6.4 (95% CI: 2.0, 20.6; P=0.002) when comparing participants in the highest pMRCI quartile with those in the lowest quartile., Conclusions: Higher pMRCI for non-ART medications is associated with lower adherence as measured by TFV-DP in DBS. Future research should investigate whether reducing non-ART medication complexity improves ART adherence and exposure in PWH., (© 2020 Pharmacotherapy Publications, Inc.)