A phase 3, open-label, follow-up study to protocol HIV-NAT 002.1 to explore the durability of the antiretroviral efficacy and durability of ddI/d4T and AZT/3TC in a population originally treated with ddI/d4T, and explore the efficacy of adding hydroxyurea to failing therapy with two nucleosides

Study objective:

  • To determine durability of the virological and immunological responses of participants on study 002.1 who were responders at week 96 and continued wirh 002.1 study medication
  • To switch those failing AZT/3TC at or before week 96 back to ddI/d4T (if responders to ddI/d4T at time of first switch) to determine to what extent they may still benefit form ddI/d4T
  • To add hydroxyurea to the last double nucleoside combination in those who have failed both ddI/d4T and AZT/3TC at week 96
  • To evaluate the efficacy and tolerability of hydroxyurea added to two failing double nucleoside combinations

Study design:

  • All consenting participants enrolled in protocol 002.1 who successfully completed 96 weeks on protocols 002 and 002.1 without significant toxicities were eligible to enroll in study HIV-NAT 002.2
  • Participants still responding to ddI/d4T ot AZT/3TC at week 96 remained on current medication.
  • Participants switched to AZT/3TC while still responding to ddI/d4T at week 48 (early switchers) ad who are failing AZT/3TC at week their 88 visit or in the course of 002.2 are switched back to ddI/d4T at the first following visit
  • Participants who at any timepoint during study 002.2 have failed both ddI/d4T and AZT/3TC will have hydroxyurea (500 mg BID) added to their last taken double nucleoside combination at first following visit.
  • Failure defined as viral load at any visit of 1 log10 or greater above the nadir reached on the current regimen or a decline in CD4+ cell count of > 30% from baseline (week 0) that is deemed significant by the investigator.

Preliminary result:

  • 69 patients still on study
  • Tweo participants have had hydroxyurea added, one to failing AZT/3TC therapy and one to a failing ddI/d4T regimen.
  • Other results pending.