A 35-Year Review of Pre-Clinical HIV Therapeutics Research Reported by NIH ChemDB: Influences of Target Discoveries, Drug Approvals and Research Funding.

We present a retrospective analysis of trends in human immunodeficiency virus (HIV) small molecule drug development over the last thirty-five years based on data captured by ChemDB, a United States (US) National Institutes of Health (NIH) database of chemical and biological HIV testing data. These data are analyzed alongside NIH funding levels, US Food and Drug Administration (FDA) drug approvals, and new target identifications to explore the influences of these factors on anti-HIV drug discovery research. The NIH's ChemDB database collects chemical and biological testing data describing published and patented pre-clinical compounds in development as potential HIV therapeutics. These data were used as a proxy for estimating overall levels of HIV therapeutics research activities in order to assess research trends. Data extracted from ChemDB were compared with records of drug approvals from the FDA, NIH funding levels, and drug target discoveries to elucidate the influences that these factors have on levels of HIV therapeutics research activities. Despite the increasingly wide suite of HIV therapeutic options that have accumulated during decades of research, interest in HIV therapeutics research activities remains strong. While decreases in research activity levels have followed cuts in research funding, FDA-approved HIV therapeutics have continued to accumulate. The comparisons presented here indicate that HIV drug research activity levels have historically been more responsive to changes in funding levels and the identification of new drug targets, than they have been to drug approvals. Continued interest in HIV therapeutics research may reflect that fact that of the 55 drugs approved for HIV treatment as of 2018, only seven inhibitory targets are represented. Moreover, drug resistance presents substantial clinical challenges. Sustained research interest despite drug approvals and fluctuations in available funding likely reflects the clinical need for safer, more palatable and more efficacious therapeutics; robust attention to both novel therapeutics and inhibitory targets is necessary given the speed of development of drug-resistant HIV strains. Only with such continued interest will we reduce the burden of acquired immunodeficiency syndrome (AIDS) disease and control the AIDS epidemic.

Estimating Risk of Hematopoietic Acute Radiation Syndrome in Children.

Following a radiological terrorist attack or radiation accident, the general public may be exposed to radiation. Historically, modeling efforts have focused on radiation effects on a "reference man"-a 70-kg, 180-cm-tall, 20- to 30-y-old male-which does not adequately reflect radiation hazard to special populations, particularly children. This work examines the radiosensitivity of children with respect to reference man to develop a set of parameters for modeling hematopoetic acute radiation syndrome in children. This analysis was performed using animal studies and the results verified using data from medical studies. Overall, the hematopoietic system in children is much more radiosensitive than that in adults, with the LD50 for children being 56% to 91% of the LD50 of adults, depending on age.