Is it time to retire AZT as a first-line treatment against HIV? That’s what treatment wonks are wondering as they worry over data presented by Dr. Eric Arts in June at the first-ever International Workshop on HIV Drug Resistance. Arts, a Case Western University researcher, found in study subjects that resistance to AZT also confers resistance to two other nucleoside analogs, ddI and ddC. “This could be very detrimental to new therapies combining AZT with another nuke and a protease inhibitor,” Arts said, adding that every AZT-based “triple threat” therapy - the most widely prescribed of all combos - may equal nothing more than protease monotherapy. And, as the new federal guidelines warn, single-drug therapy is the royal road to viral resistance and treatment failure. The upbeat note in Arts’ feather-ruffling news? 3TC, Glaxo Wellcome’s number-two nuke, is apparently free of AZT-caused cross-resistance.

AZT took another hit in August when German researchers announced they found a fatal flaw in the compound that queers the body’s ability to metabolize it. Add this to the cross-resistance crisis, many treatment activists say, and you have a good case for choosing d4T, the rival thymidine-analog nucleoside, over AZT for use in combination with the other class of nukes (ddI, ddC, 3TC) and a protease inhibitor.