Abstract

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Comparable virologic response and in vitro susceptibility to darunavir in patients infected with subtype B and non-subtype B HIV isolates participating in the ARTEMIS Phase III Trial

I. Dierynck¹, S. De Meyer¹, E. Lathouwers¹, C. Vanden Abeele¹, T. Van De Casteele¹, R. DeMasi², A. Hill³, S. Spinosa-Guzman¹, M.-P. de Béthune¹, G. Picchio²

¹Tibotec BVBA, Mechelen, Belgium, ²Tibotec Inc, Yardley, United States, ³University of Liverpool, Liverpool, United Kingdom

Background: ARTEMIS is an ongoing Phase III study assessing efficacy and safety of darunavir with low-dose ritonavir (DRV/r) versus lopinavir with low-dose ritonavir (LPV/r) in treatment-naïve patients. In the primary Week 48 analysis, DRV/r achieved a virologic response (VL<50 copies/mL) of 84% versus 78% for LPV/r. Effect of HIV-1 subtype on virological response and in-vitro susceptibility to DRV was studied in this trial.
Methods: Patients were randomized to receive DRV/r 800/100mg once-daily or lopinavir/r 800/200mg total daily dose, plus a fixed background regimen (TDF and FTC). Genotyping, subtype determination, and phenotyping (Antivirogram) were performed by Virco.
Results: Most patients (61%) harbored HIV-1 subtype B; other prevalent subtypes found were subtype C (13%) and CRF01_AE (17%); 9% harbored other subtypes. Baseline VL and CD4 counts were similar between subgroups. Virologic responses in subgroups and treatment arms are summarized (Table):

		VL<50 copies/mL at Week 48 n/N (%)
	N	DRV/r	LPV/r	Difference in response DRV/r−LPV/r % (95% CI)
Overall (ITT-TLOVR)	689	287/343 (84)	271/346 (78)	5 (−0.5, 11.2)
HIV-1 subtype
B	418	171/210 (81)	162/208 (78)	4 (−4.2; 11.3)
C	89	34/39 (87)	41/50 (82)	5 (−10.2; 20.6)
CRF01_AE	117	53/62 (85)	45/55 (82)	4 (-9.8; 17.2)

In the DRV arm, the difference [95% CI] in response among patients with subtype C and CRF01_AE versus subtype B infection was 6% [−7.3; 18.8] and 4% [−6.8; 14.9], respectively. Median EC₅₀ values (range) for DRV were similar for subtype C (1.12 nM [0.23-3.46]) and subtype CRF01_AE (1.27 nM [0.35-4.30]) compared to subtype B (1.79 nM [0.38-5.07]) HIV-1 isolates.
Conclusions: In ARTEMIS, once-daily DRV/r treatment was equally effective, irrespective of HIV-1 subtype confirming the broad activity of DRV/r. Accordingly, in vitro susceptibility to DRV was comparable across the HIV-1 subtypes studied.

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