Table 2.
Pivotal Efficacy Trials of Nucleos(t)ide Reverse Transcriptase Inhibitors in Treatment-Naïve Patients
| Trial(Reference) (N) |
Randomization arms | Primary efficacy end- point |
Primary efficacy outcome |
Comments |
|---|---|---|---|---|
| ACTG 384 (50) (980) | d4T / ddI + EFV d4T / ddI + NFV AZT/3TC+EFV AZT/3TC + NFV d4T / ddI + NFV + EFV AZT/3TC + NFV + EFV |
Failure of two consecutive three-drug regimens, failure of a single four-drug regimen, or premature discontinuation of the study treatment for any reason | The combination of AZT/3TC+EFV had superior virologic activity and safety profile compared to the other regimens | No benefits of the four drug regimens over AZT/3TC+EFV |
| GS 903 (60) (602) | d4T/3TC+EFV TDF/3TC+EFV |
VL < 400 copies/mL at week 48 using ITT analysis | 84% of patients on d4T/3TC+EFV and 80% of patients on TDF/3TC+EFV had VL below 400 copies / mL at week 48 | TDF combination did not meet criteria for equivalence at week 48 for the primary endpoint but equivalence was demonstrated using VL < 50 c/mL.TDF was associated with better lipid profiles, less lipodystrophy and equivalent efficacy in long-term follow up |
| GS 934 (61) (517) | AZT/3TC+EFV TDF/FTC+ EFV |
VL < 400 c/mL at week 48 in TLOVR analysis | 73% of patients on AZT/3TC+EFV and 84% on TDF/FTC+ EFV met primary efficacy end-point at week 48 | TDF/FTC was virologically noninferior to AZT/3TC and had significantly less adverse events. No K65R in TDF arm |
| ACTG 5175 (103) PEARLS (1571) | AZT/3TC/EFV TDF/FTC/EFV ddI/FTC/ATV |
Time to treatment failure = confirmed VL > 1,000 c/mL at or after week 16 | No significant difference in time to virologic failure between AZT/3TC and TDF/FTC groups | ddI/FTC+ ATV arm discontinued due to inferior efficacy |
| ACTG 5202 (84) (1858) | ABC/3TC + EFV or ATV TDF/FTC + EFV or ATV |
Time to virologic failure = confirmed VL ≥1000 c/mL at or after 16 weeks and before 24 weeks or ≥200 c/mL at or after 24 weeks. | Time to Virologic failure was significantly shorter in the ABC/3TC than TDF/FTC arm (HR=2.33, 95% CI 1.46–3.72), occurring in 57 and 26 subjects respectively | ABC/3TC arm terminated because of high virologic failure rate in patients with baseline VL > 100, 000 c/mL |
| CNA30024 (71) (649) | ABC/3TC+ EFV AZT/3TC+EFV |
VL < 400 copies/mL at week 48 in TLOVR analysis | 70% of patients on ABC/3TC+ EFV and 69% of patients on AZT/3TC+EFV had VL less than 400 / mL at week 48 | ABV demonstrated noninferior virologic activity and CD4 count appreciation compared to ZDV |
| HEAT (72) (688) | ABC/3TC+ LPV/r TDF/FTC+ LPV/r |
Proportion with VL < 50 c/mL at week 48 in ITT analysis | 68% of patients on ABC/3TC+ LPV/r had VL less than 50 copies/ml compared to 67% in patients on TDF/FTC+ LPV/r | TDF/FTC demonstrated non-inferior virologic activity compared to ABC/3TC |
VL: (plasma HIV-1 RNA, viral load)
ITT: intent-to-treat
TLOVR: Time to loss of virologic response
ABC- abacavir, ATV- atazanavir, AZT- zidovudine, ddI- didanosine, d4T- stavudine, EFV- efavirenz, FTC- emtricitabine, NFV- nelfinavir, TDF- tenofovir, 3TC-lamivudine