New Drug Classes with Novel Mechanisms of Action for HIV, Hepatitis B, and Tuberculosis

Fast Track Proposals will be accepted. Direct-to-Phase II proposals will not be accepted. Number of anticipated awards: 3-7 Budget (total costs): Phase I: $ 300,000 per year for up to 2 years Phase II: $ 2 million total for up to 3 years Background For more than three decades, NIH has fostered and promoted the development of therapies that have transformed human immunodeficiency virus (HIV) from an almost uniformly fatal disease into a manageable condition. Today, with combination drug treatments started early following acquisition, people living with HIV (PLWH) can expect a near-normal lifespan with the possibility of a cure. NIH has made similar investments into drug development for Hepatitis B virus (HBV) and Mycobacterium tuberculosis (Mtb), two diseases for which PLWH experience worse outcomes than people not living with HIV. Still, worldwide eradication of HIV, HBV, or Mtb has not been achieved due to significant limitations, such as non-adherence to therapy, cellular toxicity, restricted bioavailability of antiviral or anti-infective drugs, and the emergence of drug-resistant strains. Moreover, the persistence of reservoirs, even under antiviral or anti-infective drug pressure, is the major obstacle to a cure for each disease. Currently, promising therapeutic strategies are being explored. Therefore, advancing preclinical testing approaches has become an important step for drug discovery and development, continuously demanding innovative but less time-consuming evaluation strategies. Furthermore, recent advances in artificial intelligence (AI) and machine learning (ML) offer new avenues for identifying new drug classes and novel targets for therapeutic intervention