Table 4. Summary of Phase III trials.
| Phase III Study (sample size) | Proportion of patients with HIV-1 RNA <50 (copies/ml) | Proportion of patients with HIV-1 RNA <400 (copies/ml) | Mean decline in HIV-1 RNA (log10 copies/ml) | CD4 cell count increase from baseline (cells/μl) | Ref. |
|---|---|---|---|---|---|
| DUET-1 – 24 weeks | ETR: 170/304 (56%) | ETR: 224/304 (74%) | ETR: 2.41 | ETR: 89 | [29] |
| (n = 612) | PLB: 119/308 (39%) | PLB: 158/308 (51%) | PLB: 1.70 | PLB: 64 | |
| p = 0.005 | p = 0.0001 | p <0.0001 | p = 0.0002 | ||
| DUET-2 – 24 weeks | ETR: 183/295 (62%) | ETR: 221/295 (75%) | ETR: 2.34 | ETR: 78 | [30] |
| (n = 591) | PLB: 129/296 (44%) | PLB: 159/296 (54%) | PLB: 1.68 | PLB: 66 | |
| p = 0.0003 | p = 0.0001 | p <0.0001 | p = 0.3692 | ||
| Pooled DUET-1 & DUET-2 – 24 weeks | ETR: 353/599 (59%) | ETR: 443/599 (74%) | ETR: 2.37 | ETR: 81 | [31] |
| (n = 1203) | PLB: 248/604 (41%) | PLB: 317/604 (53%) | PLB: 1.69 | PLB: 64 | |
| p <0.0001 | p <0.0001 | p <0.0001 | p = 0.0022 | ||
| Pooled DUET-1 & DUET-2 – 48 weeks | ETR: 363/599 (61%) | ETR: 424/599 (72%) | ETR: 2.25 | ETR: 98 | [28] |
| (n = 1203) | PLB: 239/604 (40%) | PLB: 283/604 (47%) | PLB: 1.49 | PLB: 73 | |
| p <0.0001 | p < 0.0001 | p <0.0001 | p = 0.0006 | ||
Study design is identical for all the above Phase III studies: double blind, placebo controlled, 1:1 randomization of treatment experienced patients with first-generation non-nucleoside reverse transcriptase inhibitor resistance and at least three primary protease inhibitor mutations; randomized to ETR or PLB arms with a background regimen of darunavir/ritonavir, optimized nucleoside reverse transcriptase inhibitors, and optional enfuvirtide. Primary outcome: HIV RNA <50 copies/ml at week 24, intent-to-treat analysis. Note that the overall DUET-1 and DUET-2 primary outcomes were the week 24 analyses. Pooled and 48-week results were from subsequent analyses.
ETR: Etravirine; PLB: Placebo.