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In vitro susceptibility and virological outcome to darunavir and lopinavir are independent of HIV type-1 subtype in treatment-naive patients

2010; SAGE Publishing; Volume: 15; Issue: 8 Linguagem: Inglês

10.3851/imp1697

2040-2058

Inge Dierynck, Sandra De Meyer, Erkki Lathouwers, Carline Vanden Abeele, Tom Van de Casteele, Sabrina Spinosa‐Guzman, Marie‐Pierre de Béthune, Gastón Picchio,

HIV/AIDS Research and Interventions

Background The effect of HIV type-1 (HIV-1) subtype on in vitro susceptibility and virological response to darunavir (DRV) and lopinavir (LPV) was studied using a broad panel of primary isolates, and in recombinant clinical isolates from treatment-naive, HIV-1-infected patients in the Phase III trial, AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS). Methods Patients received DRV/ritonavir (DRV/r) 800/100 mg once daily ( n=343) or LPV/ritonavir (LPV/r) 800/200 mg total daily dose ( n=346), plus a fixed daily dose of emtricitabine and tenofovir disoproxil fumarate. Results DRV demonstrated high antiviral activity against a broad panel of HIV-1 major group (M) and outlier group (O) primary isolates in peripheral blood mononuclear cells, with a median 50% effective concentration (EC 50 ) of 0.52 nM. Most (61%) patients in ARTEMIS harboured HIV-1 subtype B; other prevalent subtypes were C (13%) and CRF01_AE (17%); 9% harboured other subtypes. Median EC 50 values (interquartile range) for DRV were 1.79 nM (1.3–2.6) for subtype B, 1.12 nM (0.8–1.4) for C and 1.27 nM (1.0–1.7) for CRF01_AE. Virological response to DRV/r (HIV-1 RNA<50 copies/ml [intent-to-treat, time-to-loss of virological response algorithm]) was 81%, 87% and 85% for patients with subtype B, C and CRF01_AE infections, respectively. Similar results were observed in the LPV/r treatment group. Conclusions In vitro susceptibility to DRV was comparable across HIV-1 subtypes in a broad panel of primary isolates and in recombinant clinical isolates. Once daily DRV/r 800/100 mg and LPV/r 800/200 mg were highly effective in ARTEMIS irrespective of the HIV-1 subtype studied, confirming their broad anti-HIV-1 activity.