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ATRIPLA: Simplification of Antiretroviral Therapy with Efavirenz/Emtricitabine/Tenofovir DF Single Tablet Regimen vs. Continued Unmodified Antiretroviral Therapy in Virologically-Suppressed, HIV-1-Infected Patients
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Reported by Jules Levin
ICAAC/IDSA, Oct 27, 2008 Wash DC
E DeJesus,1 B Young,2 J Flaherty,3 R Ebrahimi,3 J-F Maa,4 D McColl,3 D Seekins,4 and A Farajallah4 for the AI266073 Study Group
1Orlando Immunology Center, Orlando, FL; 2Denver Infectious Disease Consultants, Denver, CO; 3Gilead Sciences, Inc., Foster City, CA; 4Bristol-Myers Squibb, Princeton, NJ
BACKGROUND
Co-formulated EFV/FTC/TDF is the fi rst once daily single tablet antiretroviral (ARV) regimen approved in the United States, Canada, and the EU
The components have demonstrated long-term effi cacy and safety in treatment naive patients (Arribas JR et al. JAIDS 2008;47:74-78)
The objective of this study was to evaluate whether virologicallysuppressed patients who simplified their current ARV regimen to a single tablet regimen of EFV/FTC/TDF would have similar effectiveness (efficacy, safety and tolerability) compared to patients who remained on their unmodified ARV regimen through 48 weeks
AUTHOR CONCLUSIONS
In this study of virologically suppressed patients, through 48 weeks:
High rates of virologic suppression were maintained in both treatment arms
Simplification to EFV/FTC/TDF was well tolerated with low rates of discontinuations observed in both treatment arms
Consistent with previous reports, the most frequently reported AEs in the EFV/FTC/TDF arm were nervous system symptoms primarily in patients naïve to EFV
- These were transient, generally mild, and resulted in few treatment discontinuations
Renal function remained stable through 48 weeks, including patients naïve to TDF at baseline
Baseline adherence was high and remained high in both treatment arms
Among patients randomized to EFV/FTC/TDF, 91% indicated a preference for the single tablet regimen compared to prior therapy, and 97% found EFV/FTC/TDF easy to take
Key Inclusion / Exclusion Criteria
· HIV-1 RNA < 200 copies/mL for ≥ 3 months on current ARV regimen
· Receiving fi rst ARV regimen, or documented suppression on a previous PI-based regimen at time of prior change in therapy
· Calculated CrCL ≥ 60 mL/min (by Cockcroft-Gault formula)
· Patients with known resistance to study agents at any time in the past, and those receiving the individual components of the single tablet regimen (EFV+FTC+TDF) were excluded
Study Assessments
· HIV-1 RNA, CD4 count, chemistries, CBC performed at baseline and Weeks 4, 12, 24, 36, and 48
· GFR estimated by calculated CrCL (Cockcroft-Gault) and Modifi ed Diet in Renal Disease (MDRD)
· Select patient-reported outcomes:
- Adherence by visual analog scale
- Preference of Medication questionnaire (EFV/FTC/TDF arm only)
- Perceived Ease of Regimen for Condition survey
Statistical Methods
· Assessments were based on intent-to-treat (ITT) analysis*
· Primary endpoint was maintenance of virologic suppression defi ned as the proportion of patients with HIV-1 RNA < 200 copies/mL on their original assigned regimen through 48 Weeks based on TLOVR algorithm and assuming that non-completers = failures (NC=F)
- Responders defi ned as those with HIV-1 RNA < 200 copies/mL at Week 48 without an HIV-1 RNA value ≥ 200 copies/mL on 2 successive occasions, or without having the last HIV-1 RNA value ≥ 200 copies/mL while on-study followed by discontinuation
- The EFV/FTC/TDF arm was declared to be non-inferior to the SBR arm if the lower confi dence boundary of the responder difference (EFV/FTC/TDF - SBR) was greater than _0.15. Sample size was estimated using a non-inferiority margin (Δ) of 15% at 80% power
*ITT population included all patients randomized and who received at least one
dose of study medication
Fasting Lipid Results
· For the overall study population, no differences were observed between arms at Week 48 in median change from baseline in total cholesterol, LDL-cholesterol, or total cholesterol/HDL ratio
· The median (IQR) change from baseline in HDL-cholesterol at Week 48 for patients in the prior PI stratum was 5.0 (3, 7) mg/dL for EFV/FTC/TDF vs. 0 (-1, 5) mg/dL for SBR (p = 0.044); for this stratum there was also a trend toward improvement in total cholesterol/HDL ratio (p = 0.092)
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