GW's Nucleoside 1592U89 Shows Early Promise

Glaxo Wellcome's new reverse transcriptase inhibitor 1592U89 has achieved potent suppression of HIV replication when given either alone or in combination with Retrovir (zidovudine), according to preliminary data from an 80-patient Phase I/II study.

The initial indications are that the drug, even when given as a monotherapy, can suppress viral replication as well as the much-touted protease inhibitors, and much better than zidovudine as monotherapy. If the drug offers this degree of potency without the drawback of rapid resistance emergence which plagued the early development the protease inhibitors, it may emerge as an important new drug for HIV infection.

100-Fold Reduction 1592U89 was given alone (200mg or 400mg three-times daily) for four weeks, and then for eight weeks in combination with either Retrovir or placebo. At the end of the four-week lead-in, the patients experienced a median decrease in viral load of almost 99% (1.5-2.2 log reduction), accompanied by a median 79-127/mm3 increase in CD4 cell counts. Viral load fell below detectable limits (200 copies/ml) for 2/15 patients in the 200mg group and 4/15 patients in the 400mg group.