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This combination therapy, consisting of the anti-tuberculosis agent pyrazinamide and the antimalarial/immunomodulator hydroxychloroquine, is being developed by the Ministry of Health, Saudi Arabia, for the treatment of newly diagnosed drug-sensitive pulmonary tuberculosis. The regimen utilizes an AI-optimized dosing schedule (AIPH-TB framework) designed to maximize the synergistic interaction between the two drugs. Hydroxychloroquine acts as a synergistic adjuvant by inhibiting the BCRP-1 (ABCG2) efflux pump and raising phagolysosomal pH, which significantly increases the intracellular concentration and bactericidal activity of pyrazinamide against *Mycobacterium tuberculosis*. This approach aims to improve cure rates and reduce drug-induced hepatotoxicity compared to the standard four-drug RIPE regimen.
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