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  9th International Congress on Drug Therapy in HIV Infection
November 9-13, 2008
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Simplification of Antiretroviral Therapy with Efavirenz/Emtricitabine/Tenofovir DF Single Tablet Regimen vs. Continued Antiretroviral Therapy in Suppressed, HIV-1-Infected Patients
  Reported by Jules Levin
9th International Congress on Drug Therapy in HIV Infection
November 9-13, 2008 Glasgow, UK
B Young,1 E DeJesus,2 J Morales-Ramirez,3 J Flaherty,4 R Ebrahimi,4 J-F Maa,5 D McColl,4 D Seekins,5 and A Farajallah5 for the AI266073 Study Team 1Denver Infectious Disease Consultants, Denver, CO; 2Orlando Immunology Center, Orlando, FL; 3Clinical Research Puerto Rico, San Juan, PR; 4Gilead Sciences, Inc., Foster City, CA; 5Bristol-Myers Squibb, Princeton, NJ
Co-formulated EFV/FTC/TDF is the first once daily single tablet antiretroviral (ARV) regimen approved in the United States, Canada, and the EU
The components have demonstrated long-term efficacy and safety in treatment naive patients (Arribas JR et al. JAIDS 2008;47:74-78)
This study evaluated whether suppressed patients who simplify therapy to a single tablet regimen of EFV/FTC/TDF have similar effectiveness (efficacy, safety and tolerability) vs. patients who remain on their unmodified ARV regimen through 48 weeks
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
Patients randomized to EFV/FTC/TDF, particularly those on a prior PI containing regimen, showed significant declines in triglycerides compared to unmodified therapy
Key Inclusion / Exclusion Criteria

HIV-1 RNA < 200 copies/mL for ≥ 3 months on current ARV regimen
Receiving first 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 and those receiving 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 Modified Diet in Renal Disease (MDRD)
Patient-reported outcomes:
-- Refer to Poster # P063 (Hodder S, et al.)
Statistical Methods
Sample size was estimated using a non-inferiority margin ∇ of 15% at 80% power. EFV/FTC/TDF was to be declared non-inferior to SBR if the lower confi dence boundary of the difference (EFV/FTC/TDF - SBR) for the primary endpoint was greater than -0.15
Assessments were based on intent-to-treat (ITT) analysis*
Primary endpoint: HIV-1 RNA < 200 copies/mL through 48 Weeks based on TLOVR, assuming non-completers equal failures (NC=F)
-- Responders were those with HIV-1 RNA < 200 copies/mL at Week 48 without HIV-1 RNA ≥ 200 copies/mL on 2 successive occasions, or without last HIV-1 RNA ≥ 200 copies/mL while on-study followed by DC
Secondary endpoints were the proportion of patients with HIV-1 RNA <50 copies/mL by: TLOVR (NC=F), Pure Virologic Response (PVR) [estimated by Kaplan-Meier where responders were defi ned as those without 2 consecutive HIV-1 RNA ≥50 copies/mL or without last HIV-1 RNA ≥50 copies/mL followed by DC], and Last Observation Carried Forward (LOCF)** [where those with HIV-1 RNA ≥50 copies/mL or those who DC early due to an adverse event were treated as failures]
*ITT population included all patients randomized and who received at least one dose of study medication
**LOCF endpoint was defi ned post-hoc





CD4 Responses
Median change from baseline in CD4 cell count at Week 48 was 3 cells/μL and 9 cells/μL for EFV/FTC/TDF and SBR, respectively