New questions about an old combination--ddI + d4T.

For the last several years, the combination of ddI (didanosine, Videx) and d4T (stavudine, Zerit) as a backbone of three-drug therapy has been popular both in treatment and in research. Together, the two nucleoside analog reverse transcriptase inhibitor (NARTI) drugs offered relatively high strength and fairly simple use. Despite this, some researchers have long questioned the wisdom of the combination as it violates one of the key rules of combining drugs: combine only drugs with different side effect profiles. Both drugs are associated with the development of peripheral neuropathy and pancreatitis. Pancreatitis is more commonly seen with ddI and neuropathy with d4T, but both occur to a significant degree with each drug and to a higher degree than was seen with other drugs of their class. However, few if any studies were run comparing the ddI/d4T combination to alternatives such as AZT/3TC (Combivir) or even 3TC/d4T. Both ddI and d4T come from the same company, Bristol Myers Squibb.