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Quantum relative entropy (QRE) programming is a recently popular and challenging class of convex optimization problems with significant applications in quantum computing and quantum information theory. We are interested in modern interior-point (IP) methods based on optimal self-concordant barriers for the QRE cone. A range of theoretical and numerical challenges associated with such barrier functions and the QRE cones have hindered the scalability of IP methods. To address these challenges, we propose a series of numerical and linear algebraic techniques and heuristics aimed at enhancing the efficiency of gradient and Hessian computations for the self-concordant barrier function, solving linear systems, and performing matrix-vector products. We also introduce and deliberate about some interesting concepts related to QRE such as symmetric quantum relative entropy. We design a two-phase method for performing facial reduction that can significantly improve the performance of QRE programming. Our new techniques have been implemented in the latest version (DDS 2.2) of the software package Domain-Driven Solver (DDS). In addition to handling QRE constraints, DDS accepts any combination of several other conic and nonconic convex constraints. Our comprehensive numerical experiments encompass several parts, including (1) a comparison of DDS 2.2 with Hypatia for the nearest correlation matrix problem, (2) using DDS 2.2 for combining QRE constraints with various other constraint types, and (3) calculating the key rate for quantum key distribution (QKD) channels and presenting results for several QKD protocols.