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.