This study will explore whether HIV replication can be reduced to very low levels and potentially eradicated through the use of potent induction therapy with zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV) followed by less potent maintenance therapy. This is an investigator-initiated NIH-sponsored phase II, prospective, randomized, double-blind study of subjects with >1,000 copies/ml of HIV RNA and >200 CD4 cells/mm3. 300 subjects will receive open-label induction therapy with ZDV 300 mg BID, 3TC 150mg BID, and IDV 800mg TID for 6 months (24 weeks). Following this 6 month Induction Phase (Part 1), subjects with undetectable plasma HIV RNA at weeks 16, 20, and 24 will enter the Maintenance Phase (Part II) and be randomized to one of three maintenance double-blind regimens; ZDV/3TC vs. ZDV/3TC vs IDV monotherapy for 12 months (48) weeks). The Roche Amplicor assay (presently approved to quantitate HIV RNA to a lower level of 500 copies/ml) will be used to measure plasma HIV RNA in this protocol. If the Roche standard assay or the ultradirect assay are validated to sensitivity and specificity levels below 500 copies/ml prior to the first subject being randomized to maintenance therapy, the lower threshold in defining undetectable' will be modified accordingly. After 12 months of maintenance therapy, therapy will be withdrawn in 120 randomly selected subjects (20 in each arm at both 72 and 96 weeks of total therapy) in the Maintenance/Withdrawal Phase (Part III). Subjects not withdrawn from therapy will continue on their blinded Maintenance Phase medications for the remainder of the study (18 months/72 weeks). Subjects who develop intolerance to zidovudine may substitute stavudine.
Showing the most recent 10 out of 1065 publications
