A randomized, double-blind, comparative trial to evaluate the efficacy of combination therapy with AZT 200 mg TID plus ddC 0.75 mg TID versus AZT 100 mg TID plus ddC 0.375 mg TID in an antiretroviral- naïve Thai study population

Project no.: HIV-NAT 001

Rationale: AZT given at a doses as low as 300 mg per day may be effective in suppressing HIV-1 replication. This may be due to saturations of intra-cellular AZT phosphorylation. Further, the relatively low body weight of Thais compared to some other study populations may facilitate the use of lower doses of antiretroviral medication.

Objective: To evaluate the efficacy and tolerability of AZT/ddC in standard doses versus half standard doses.

Study Endpoints:

  • Changes in CD4+ lymphocyte count
  • Reduction in HIV-1 RNA (RT-PCR, AmplicrR, Roche)

Study Design:

  • Patients were randomized into one of two treatment arms:
    • Standard dose: AZT 200 mg TID + ddC 0.75 mg TID
    • Half dose: AZT 100 mg TID + ddC 0.375 mg TID
  • Clinical and laboratory evaluation of was performed on patients at week -2, 0, 4, 12, 24, 36, and 48
  • Plasma and serum was stored at each visit for future (genotypic) resistance assays
  • PBMCs were collected from 40 patients at weeks 4 and 24 for evaluation of intracellular AZT phosphorylation.

Result:

  • HIV-1 RNA reduction was slightly but significantly greater in the standard dose arm compared to the half dose arm when a non-linear mixed affects regression model was used.
  • Individual plots of the RNA curves suggest better inhibition of HIV-1 replication in the standard dose arm at all time points in the study.
  • Results of genotypic resistance assays and AZT phosphylation assays are pending.
  • At 48 weeks, there no stastically significant differences in adverse events between the two groups.