H-1233. Characterization of Virologic Failure (VF) Over 96 Weeks by Drug Resistance and Antiviral Response in ART Naïve Patients Receiving Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC) Each with Lopinavir/Ritonavir QD in the HEAT Study
Session: Poster Session: Antiretroviral Therapy: Clinical Trials
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: HEAT is a randomized, double-blind, placebo-matched, multi-center, 96-week study in ART naïve, HIV-1 infected subjects with screening plasma HIV-1 RNA (VL)≥ 1000 copies/mL (c/mL) and any CD4+ count which demonstrated non-inferiority of ABC/3TC to TDF/FTC when given with once-daily LPV/r (%<50 c/mL at Week 48 (M=F): ABC/3TC: 68%, TDF/FTC: 67%;). At Week 48 there were 79 (12%) confirmed VFs; ABC/3TC: 12%, TDF/FTC: 13%.
Methods: VFs (failure to achieve VL <200 c/mL by Wk 24, or confirmed rebound to ≥200 c/mL) were evaluated by the PhenoSense GT™ assay at BL and time of VF. IAS-USA mutations (2007) and antiviral drug susceptibilities were tabulated.
Results: At Week 96, 14% subjects met the VF criteria (ABC/3TC:49/343, TDF/FTC:48/345). Of these 97 subjects, 45 did not achieve <200 c/mL by Wk 24 (ABC/3TC:21, TDF/FTC:24) while 52/97 experienced viral rebound over 96 weeks (ABC/3TC:28, TDF/FTC:24). For subjects experiencing VF, the median BL VLs were - ABC/3TC: 5.2, TDF/FTC: 4.8 log10 c/mL Virus from 46/86 subjects with matched BL and on-treatment genotypes had no treatment-emergent (TE) mutations at VF. TE resistance patterns seen were NRTIs (n=28), PIs (n=18), and NNRTIs (n=7). Differences between the two groups were seen in the TE mutations or mixtures at codon 184 (ABC/3TC: 11, TDF/FTC: 17), codon 65 (ABC/3TC: 0, TDF/FTC: 1) and TAMs (ABC/3TC: 2, TDF/FTC: 0). Phenotypic reduced susceptibility confirmed the importance of these genotypic findings. TE primary PI mutations were seen in 1 patient (ABC/3TC + LPVr).
Conclusions: Through 96 weeks the VF rate was comparable in the two treatment groups. Subjects receiving ABC/3TC and experiencing VF had fewer mutations at codon 184. Treatment-emergent primary PI mutations were extremely rare.
Benjamin Young, MD PhD1, Cindy Vavro2, Daniel Berger, MD3, Kimberly Smith, MD, MPH4, Linda Yau2, Martin Markowitz, MD PhD5, Parul Patel, PharmD6, Paul Wannamaker2 and  B. Young,
Bristol-Myers Squibb Company Role(s): Consultant, Received: Grant Recipient, Consulting Fee.
Cerner Corporation Role(s): Consultant, Received: Grant Recipient, Consulting Fee.
Gilead Sciences Role(s): Consultant, Speaker's Bureau, Received: Grant Recipient, Consulting Fee.
GlaxoSmithKline Role(s): Consultant, Speaker's Bureau, Received: Research Grant, Consulting Fee.
Hoffman-LaRoche Role(s): Consultant, Received: Grant Recipient, Consulting Fee.
Merck & Co Role(s): Consultant, Speaker's Bureau, Received: Grant Recipient, Consulting Fee.
Monogram Biosciences Role(s): Consultant, Speaker's Bureau, Received: Consulting Fee.
Pfizer Role(s): Consultant, Received: Consulting Fee.
Vertex Pharmaceuticals Role(s): Consultant, Speaker's Bureau, Received: Consulting Fee., (1)Denver ID Consult, Denver, CO, (2)GSK, (3)North Star Medical Center, Chicago, IL, (4)Rush University Medical Center, Chicago, IL, (5)ADARC, (6)GlaxoSmithKline


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