In the Mismatch: Viral Suppression Despite Low Tenofovir-Diphosphate in Dried Blood Spots in the Multicenter AIDS Cohort Study/Women’s Interagency HIV Study Combined Cohort

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Abstract
Background: Tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) is an objective drug concentration measure which is predictive of future viremia in virally-suppressed persons with HIV (PWH) on TFV-based antiretroviral therapy (ART). Viral load (VL):TFV-DP mismatch (suppressed VL despite low TFV-DP concentrations) may increase future viremia risk. Previously, Black race, male sex, and higher body mass index were associated with lower TFV-DP concentrations among PWH receiving tenofovir disoproxil fumarate (TDF). The aim of this study was to assess mismatch rates in PWH on tenofovir alafenamide (TAF). Methods: DBS samples were obtained from Multicenter AIDS Cohort Study/Women’s Interagency HIV Study Combined Cohort participants receiving TAF-based ART for ≥3 months. Associations between pre-specified covariates and pharmacologic virologic mismatch (plasma VL <200 copies/mL and intracellular TFV-DP concentrations <1800 fmol/punches), were evaluated using logistic regression. Results: DBS was measured in 627 PWH (63% female) and median [IQR] age 55 [47-61] years. TFV-DP for VL 200 copies/mL was 2,375 [1,493-3,340] and 264 [13-949] fmol/punches, respectively. Females experienced 39% mismatch. Higher estimated glomerular filtration rate (eGFR; +15 mL/minute/1.73 m2), weight (+15 kg), and lower self-reported adherence (<95%) were associated with higher mismatch odds: 1.77 (1.40-2.28), 1.32 (1.11-1.57), and 5.12 (2.16-12.90), respectively. Males experienced 27% mismatch. Higher eGFR, weight, Black race, and lower adherence were associated with higher mismatch odds: 1.75 (1.22-2.62), 1.66 (1.19-2.39), 7.53 (2.87-22.28), and 9.61 (2.17-51.95), respectively. Conclusions: Weight, eGFR, self-reported adherence and Black race in males were associated with mismatch. These characteristics should be considered when designing adherence interventions.

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