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Session 80 Poster Abstracts
Antiretroviral Therapy: Predictors of Response and Virologic Failure
Monday, 1:30 - 3:30 pm
Poster Hall


549
Final Week 48 Analysis of a Phase 4, Randomised, Open-label, Multi-center Trial to Evaluate Safety and Efficacy of Continued Lamivudine Twice Daily Versus Discontinuation of Lamivudine in HIV-1-infected Adults with Virological Failure on Ongoing Combination Treatments Containing Lamivudine: The COLATE Trial
U Dragsted*1, Z Fox1, L Mathiesen2, C Katlama3, M Youle4, J Gerstoft5, J N Bruun6, and J D Lundgren for the COLATE trial group1
1Copenhagen HIV Prgm., Hvidovre Univ. Hosp., Denmark; 2Hvidovre Univ. Hosp., Copenhagen, Denmark; 3Hosp. de la Pitié- Salpêtriére, Paris, France; 4Royal Free Hosp., London, UK; 5Rigshospitalet, Copenhagen, Denmark; and 6Ullevål Univ. Hosp., Oslo, Norway

Background: Lamivudine (3TC) is commonly used in HIV-1 treatment regimens both prior to and following virological failure. In vitro data suggest benefit of continuing 3TC after virological failure. The COLATE trial is the first randomised clinical assessment of this tx approach. The primary objective was to compare the log10 reduction in plasma viral load (pVL) following 48 weeks of tx as determined by the area under the curve changes from baseline (AAUCMB).

Method: The trial is randomized (1:1), phase 4, open-label, and multi-centre. Patients with viral failure on a 3TC containing regimen either continued (150 mg twice daily) or discontinued 3TC in the subsequent treatment regimen. Concomitant use of 3 drugs other than 3TC was decided prior to randomization. Analyses are intention-to-treat on patients exposed to the randomized treatment (ITT/e (switch included)). All patients, whether discontinued or on the randomized treatment, were followed for 48 weeks.

Results: The randomized treatment was initiated in 131/133 (98%) patients; complete follow-up data are available from 124 (95%). Patients were primarily white (82%), male (82%) homosexuals (58%) with median age of 41 (IQR: 36 to 48) years. At baseline median plasma viral load was 4.0 (IQR:  3.3 to 4.5) copies/mL, CD4 was 310 (IQR: 203 to 440) cells/mm3, CD4 nadir was 125 (IQR: 52 to 200) cells/mm3, and 33% had had a prior CDC category C disease. No difference was seen in baseline parameters between the study arms. At 48 weeks, 54 (83%) in the 3TC arm and 60 (91%) in the no-3TC arm were still on the randomized treatment. The primary reason for premature discontinuation was non-fatal adverse events (6 of 17). At week 48 the AAUCMB was -1.4 (95%CI: -1.6, -1.1) in the 3TC arm and -1.5 (95%CI: -1.7,  -1.2) in the no-3TC arm (ITT/e; p = 0.51), and 52%/66% (3TC arm) and 44%/65% (no-3TC) had plasma viral load <50/<400 copies/mL, respectively. There was no difference between the study arms in the time to protocol-defined virological failure (log rank test, p = 0.65).

Conclusions: In the COLATE trial no differences were found in primary and secondary virological efficacy analyses between HIV-1-infected patients randomised to continue or discontinue 3TC in the new regimen after virological failure had occurred on a 3TC containing regimen.

Keywords: Lamivudine; randomised; virological failure