Didanosine (ddI, DDI), marketed under the trade names Videx, is a medication used to treat HIV/AIDS. It is used in combination with other medications as part of highly active antiretroviral therapy (HAART). It is of the reverse-transcriptase inhibitor class. Didanosine (ddI, DDI), marketed under the trade names Videx, is a medication used to treat HIV/AIDS. It is used in combination with other medications as part of highly active antiretroviral therapy (HAART). It is of the reverse-transcriptase inhibitor class. Didanosine was first described in 1975 and approved for use in the United States in 1991. The most common adverse events with didanosine are diarrhea, nausea, vomiting, abdominal pain, fever, headache, and rash. Peripheral neuropathy occurred in 21-26% of participants in key didanosine trials. Pancreatitis is rarely observed but has caused occasional fatalities, and has black box warning status. Other reported serious adverse events are retinal changes, optic neuritis and alterations of liver functions. The risk of some of these serious adverse events is increased by drinking alcohol. In February 2010, the United States Food and Drug Administration issued a statement that patients using Didanosine (Videx) are at risk for a rare but potentially fatal liver disorder, non-cirrhotic portal hypertension. Drug resistance to didanosine does develop, though slower than to zidovudine (AZT). The most common mutation observed in vivo is L74V in the viral pol gene, which confers cross-resistance to zalcitabine; other mutations observed include K65R and M184V . Didanosine (ddI) is a nucleoside analogue of adenosine. It differs from other nucleoside analogues, because it does not have any of the regular bases, instead it has hypoxanthine attached to the sugar ring. Within the cell, ddI is phosphorylated to the active metabolite of dideoxyadenosine triphosphate, ddATP, by cellular enzymes. Like other anti-HIV nucleoside analogs, it acts as a chain terminator by incorporation and inhibits viral reverse transcriptase by competing with natural dATP. Oral absorption of didanosine is fairly low (42%) but rapid. Food substantially reduces didanosine bioavailability, and the drug should be administered on an empty stomach. The half-life in plasma is only 1.5 hours, but in the intracellular environment more than 12 hours. An enteric-coated formulation is now marketed as well. Elimination is predominantly renal; the kidneys actively secrete didanosine, the amount being 20% of the oral dose. The related pro-drug of didanosine, 2′,3′-dideoxyadenosine (ddA), was initially synthesized by Morris J. Robins (professor of Organic Chemistry at Brigham Young University) and R.K. Robins in 1964. Subsequently, Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan in the National Cancer Institute (NCI) found that ddA and ddI could inhibit HIV replication in the test tube and conducted initial clinical trials showing that didanosine had activity in patients infected with HIV. On behalf of the NCI, they were awarded patents on these activities. Since the NCI does not market products directly, the National Institutes of Health (NIH) awarded a ten-year exclusive license to Bristol-Myers Squibb Co. (BMS) to market and sell ddI as Videx tablets.