Tenofovir diphosphate in dried blood spots predicts future viremia in persons with HIV taking antiretroviral therapy in South Africa
Lauren Jennings, Reuben N. Robbins, Nadia Nguyen, Christopher Ferraris, Cheng-Shiun Leu, Curtis Dolezal, Nei-yuan Hsiao, Ofole Mgbako, John Joska, Jose R. Castillo-Mancilla, Landon Myer, Peter L. Anderson, Robert H. Remien, Catherine Orrell
Abstract
OBJECTIVES: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is used as a biomarker of antiretroviral therapy (ART) adherence. Recent treatment studies have shown that TFV-DP predicts future viremia in persons with HIV (PWH) but there are few data from high-burden settings. We investigated whether TFV-DP in DBS predicts future viral breakthrough in South African PWH. DESIGN: Prospective observational cohort. METHODS: We enrolled 250 adults receiving tenofovir-containing regimens, currently virally suppressed (<50 copies/ml) but at risk of future viral breakthrough, from four primary health clinics in Cape Town. Paired viral load and DBS for TFV-DP were collected monthly for 12 months. Viral breakthrough was the first confirmed viral load greater than 400 copies/ml. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals for future viral breakthrough at the next visit. RESULTS: Participants provided 2944 paired DBS and viral load samples. Median (IQR) age was 34 (27-42) years; median duration on ART at study entry was 11 (4-12) months;78% were women. Twenty-one (8%) participants developed viral breakthrough. Participants with TFV-DP 400 fmol/punch or less had an adjusted OR of 16.1 (95% CI: 3.9-67.4; P < 0.001) for developing viral breakthrough 1 month later compared with participants with TFV-DP greater 800 fmol/punch. CONCLUSION: TFV-DP in DBS strongly predicted future viral breakthrough in a clinical cohort of South African PWH. A biomarker able to identify PWH at risk for future viral breakthrough has the potential to improve health outcomes through timely intervention. Future studies exploring the clinical use of TFV-DP in DBS in conjunction with viral load in ART monitoring are warranted.