Paper # 59LB
ACTG 5202: Final Results of ABC/3TC or TDF/FTC with either EFV or ATV/r in Treatment-naive HIV-infected Patients
Eric Daar*1, C Tierney2, M Fischl3, A Collier4, K Mollan2, C Budhathoki2, C Godfrey5, N Jahed6, D Katzenstein7, P Sax8, and ACTG A5202 Study Team
1Los Angeles Biomed Res Inst at Harbor-UCLA, Torrance, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Univ of Miami Miller Sch of Med, FL, US; 4Harborview Med Ctr, Univ of Washington, Seattle, US; 5Div of AIDS, NIH, Bethesda, MD, US; 6Social & Sci Systems, Inc, Silver Spring, MD, US; 7Stanford Univ, CA, US; and 8Brigham and Women`s Hosp, Harvard Med Sch, Boston, MA, US
Background: A5202 was a randomized equivalence study
of blinded abacavir/lamivudine (ABC/3TC) or
tenofovir/emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir/ritonavir
(ATV/r). A Data Safety Monitoring Board (DSMB) previously recommended unblinding
those in high viral load (VL) stratum due to a shorter time to viral failure
(VF) for ABC/3TC than TDF/FTC. Data by nucleoside reverse transcriptase
inhibitors (NRTI) for low VL stratum and for EFV vs ATV/r comparisons are
presented.
Methods: Randomization was stratified by screening
VL (< vs ≥105 copies/mL). Primary endpoints: efficacy,
time to confirmed VF- VL ≥1000 copies/mL at 16 to 24 wks or ≥200
copies/mL at ≥24 wks; safety, time to grade 3/4 sign/symptom or lab
toxicity; and tolerability, time to change in regimen. Results for each NRTI
with EFV or ATV/r and for ATV/r vs EFV by NRTI are presented as estimated
hazard ratio (HR) with 95% confidence intervals (CI) from Cox proportional
hazards models and log rank test P-values. Equivalence boundary for
overall VF HR 95% CI was pre-specified at 0.71, 1.40 assuming 32% VF by week
96.
Results: Patients were 83% men, 33% black, 23%
Hispanic with median age 38 years, VL 4.7 log10 copies/mL, CD4 230
cells/mL, 138 weeks’ follow-up.
Comparisons of NRTI in low VL stratum and for third drugs in all patients were
not different for efficacy (see the table). In the high VL stratum, time to VF
censored at time of DSMB review was shorter for ABC/3TC than TDF/FTC with EFV
(HR 2.46, 95%CI 1.20 to 5.05) or ATV/r (HR 2.22, 95%CI 1.19 to 4.14). Safety
and tolerability results for NRTI and third drug comparisons in the low VL
stratum and for all patients, respectively, are in the table.
Conclusions: NRTI comparisons in the low VL stratum
and third drug comparisons for all patients were not demonstrably different for
time to VF but were not within pre-specified equivalence boundary; VF rates
were lower than projected. For some of the NRTI and third drug comparisons
there were significant differences in time to safety and tolerability events.
|
|
Efficacy
|
Safety
|
Tolerability
|
|
HR (95%CI)
|
% VF free at week 96
|
HR (95%CI)
|
P-value
|
HR (95%CI)
|
P-value
|
|
Screening VL<105 copies/mL (n=1060)
|
|
ATV/r with ABC/3TC vs
TDF/FTC
|
1.25
(0.76 to 2.05)
|
88 vs 90
|
1.13
(0.83 to 1.54)
|
0.44
|
1.43
(1.06 to 1.92)
|
0.018
|
|
EFV with
ABC/3TC vs
TDF/FTC
|
1.23
(0.77 to 1.96)
|
87 vs 89
|
1.38
(1.03 to 1.85)
|
0.03
|
1.48
(1.12 to 1.95)
|
0.005
|
|
All patients (n=1857)
|
|
ABC/3TC with ATV/r vs
EFV
|
1.13
(0.82 to 1.56)
|
83 vs 85
|
0.81
(0.66 to 1.00)
|
0.05
|
0.69
(0.55 to 0.86)
|
0.0008
|
|
TDF/FTC with
ATV/r vs
EFV
|
1.01
(0.70 to 1.46)
|
89 vs 90
|
0.91
(0.72 to 1.15)
|
0.44
|
0.84
(0.66 to 1.07)
|
0.17
|
|
