Associations Between Tenofovir Diphosphate in Dried Blood Spots, Impaired Physical Function, and Fracture Risk

BACKGROUND: In this study, we evaluate associations between cumulative antiretroviral adherence/exposure, quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), and human immunodeficiency virus (HIV)-related aging factors. METHODS: This is a cross-sectional analysis of younger (ages 18–35) and older (ages ≥60) persons with HIV (PWH) taking TFV disoproxil fumarate. Tenofovir diphosphate concentrations were quantified in DBS. Linear and logistic regression models were used to evaluate associations between TFV-DP and bone mineral density (BMD), physical function, frailty, and falls. RESULTS: Forty-five PWH were enrolled (23 younger, 22 older). Every 500 fmol/punch (equivalent to an increase in ~2 doses/week) increase in TFV-DP was associated with decreased hip BMD (−0.021 g/cm(2); 95% confidence interval [CI], −0.040 to −0.002; P = .03). Adjusting for total fat mass, every 500 fmol/punch increase in TFV-DP was associated with higher odds of Short Physical Performance Battery impairment (score ≤10; adjusted odds ratio [OR], 1.6; 95% CI, 1.0–2.5; P = .04). Every 500 fmol/punch increase in TFV-DP was associated with slower 400-meter walk time (14.8 seconds; 95% CI, 3.8–25.8; P = .01) and remained significant after adjusting for age, lean body mass, body mass index (BMI), and fat mass (all P ≤ .01). Every 500 fmol/punch increase in TFV-DP was associated with higher odds of reporting a fall in the prior 6 months (OR, 1.8; 95% CI, 1.1–2.8; P = .02); this remained significant after adjusting for age, lean body mass, BMI, and total fat mass (all P < .05). CONCLUSIONS: Higher TFV-DP levels were associated with lower hip BMD, poorer physical function, and greater risk for falls, a concerning combination for increased fracture risk.