[31] IMPACT OF OPTIMISED BACKGROUND REGIMEN ON VIROLOGICAL RESPONSE TO TMC-114 WITH LOW-DOSE RITONAVIR IN POWER 1, 2 AND 3, AS MEASURED BY THE PHENOTYPIC SUSCEPTIBILITY SCORE

15th International HIV Drug Resistance Workshop

13-17 June 2006, Sitges, Spain

IMPACT OF OPTIMISED BACKGROUND REGIMEN ON VIROLOGICAL RESPONSE TO TMC-114 WITH LOW-DOSE RITONAVIR IN POWER 1, 2 AND 3, AS MEASURED BY THE PHENOTYPIC SUSCEPTIBILITY SCORE

Antivir Ther. 2006, 11:S36 (abstract no. 31)

T Vangeneugden¹, B Winters², L Bacheler³, G Picchio³, M-P de Béthune¹, P McKenna² and D Miralles¹
¹Tibotec BVBA, Mechelen, Belgium; ²Virco BVBA, Mechelen, Belgium; ³VircoLab, Inc., Durham, NC, USA

BACKGROUND: TMC-114 (darunavir) with low-dose ritonavir (TMC-114/ritonavir) showed significant antiviral efficacy in treatment-experienced patients in POWER 1, 2 and 3, with 42% of patients reaching HIV RNA <50 copies/ml at Week 24. This analysis describes the impact of the baseline phenotypic susceptibility score (PSS) of the optimised background regimen (OBR, consisting of nucleoside analogues [NRTIs] with or without enfuvirtide), as determined by the linear model (LM)-based virco®TYPE HIV-1, on virological response.

METHODS: In POWER 1, 2 and 3, 458 patients initiated treatment with TMC-114/ritonavir 600/100mg twice-daily, the recommended dose for treatment-experienced patients. Week 24 and 48 virological response analyses were intent-to-treat (non-completer = failure for change in viral load [VL], and time-to-loss of virological response for the proportion reaching HIV RNA <50 copies/ml). Susceptibility of the NRTIs in the OBR was determined by LM-virco®TYPE v4.0.00. The total PSS was calculated as the sum of total NRTI PSS, +1 if enfuvirtide was used for the first time. Subgroup analyses were performed by total PSS (≤0.5, 0.5–1.5, and >1.5). Multivariate models correcting for baseline characteristics were applied to estimate the change in VL.

RESULTS: In POWER 1, 2 and 3 at baseline, 47%, 43% and 10% of patients had a PSS of ≤0.5, 0.5–1.5 and >1.5, respectively. PSS of the OBR was a strong predictor of Week 24 virological response: 34%, 49% and 52% of patients with PSS ≤0.5, 0.5–1.5 and >1.5, respectively achieved HIV RNA <50 copies/ml. A similar trend was observed in POWER 1 and 2 at Week 48 for both the control group (2%, 11% and 22%, respectively) and the TMC-114/ritonavir 600/100mg twice-daily group (28%, 60% and 56%, respectively). Similar results were observed for change in VL. Multivariate analyses correcting for other baseline prognostic factors confirmed these observations.

CONCLUSIONS: Baseline PSS of the OBR, as determined by the LM-based virco®TYPE, was a strong predictor of virological response. Response to TMC-114/ritonavir treatment in the group of patients with the lowest PSS was still higher than for control, regardless of subgroup.

2006-06-13
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