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.

Abstract

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). 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. DBS was measured in 627 PWH (63% female) and median [IQR] age 55 [47-61] years. TFV-DP for VL <200 copies/mL and 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. Weight, eGFR, self-reported adherence and Black race in males were associated with mismatch. These characteristics should be considered when designing adherence interventions.