TUAB0101 - Oral Abstract Session
Efficacy and safety of lersivirine (UK-453,061) vs. efavirenz in antiretroviral treatment-naïve HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicentre, randomised, double-blind, phase IIb trial (study A5271015)
Presented by Anton Pozniak (United Kingdom).
P. Vernazza1, C. Wang2, A. Pozniak3, E. Weil2, P. Pulik4, D. Cooper5, R. Kaplan6, A. Lazzarin7, H. Valdez8, J. Goodrich9, C. Craig10, J. Mori10, M. Tawadrous2
1Cantonal Hospital, St Gallen, Switzerland, 2Pfizer, Inc., New London, United States, 3Chelsea & Westminster Hospital, London, United States, 4Provincial Infectious Hospital of Warsaw, Warsaw, Poland, 5National Centre in HIV Epidemiology & Clinical Research, Darlinghurst, Australia, 6Desmond Tutu HIV Foundation, Cape Town, South Africa, 7Universita Vita-Salute San Raffaele, Milan, Italy, 8Pfizer, Inc., New York, United States, 9ViiV HealthCare, Research Triangle Park, United States, 10Pfizer Global Research & Development, Sandwich Laboratories, Kent, United Kingdom
Background: Lersivirine is a second-generation NNRTI with a unique resistance profile, currently under development.
Methods: Study A5271015 is an ongoing 96-week, international, double-blind, randomised, Phase IIb study in HIV-1 infected, treatment-naïve patients to assess antiviral activity and safety of lersivirine (500/750mg once daily [QD]) or efavirenz (600mg QD), each combined with tenofovir DF/emtricitabine (300mg/200mg QD). Primary endpoint was percentage of patients with HIV-1 RNA < 50 copies/mL (missing/discontinuation=failure) at 48 weeks.
Results: Overall, 193 patients were randomised 1:1:1 and received study treatment. Baseline mean viral load was 4.7 log10 copies/mL; median CD4+ cell count 310 cells/mm3. Percentage of patients with HIV-1 RNA < 50 copies/mL was 51/65 (79%), 51/65 (79%) and 54/63 (86%) in lersivirine 500mg, 750mg and efavirenz groups, respectively. CD4+ cell count changes from baseline were similar across groups: lersivirine 500mg: +194.2 cells/mm3, 750mg: +199.4 cells/mm3, efavirenz: +196.7cells/mm3 Most common adverse events (AEs, all causalities) with efavirenz were abnormal dreams (8% lersivirine 500mg, 8% 750mg, 19% efavirenz) and dizziness (8% lersivirine 500mg, 6% 750mg, 21% efavirenz). Most common AEs with lersivirine were nausea (23% lersivirine 500mg, 42% 750mg, 13% efavirenz) and headache (23% lersivirine 500mg, 17% 750mg, 14% efavirenz). Rash and grade 3/4 AEs were less frequent with lersivirine than efavirenz (rash: 5% lersivirine 500mg, 2% 750mg, 11% efavirenz; grade 3/4 AEs: 6% lersivirine 500mg, 14% 750mg, 22% efavirenz). AE-related discontinuations occurred in 3 (lersivirine 500mg), 3 (750mg) and 5 (efavirenz) patients. Few clinically significant laboratory abnormalities were reported. Lersivirine was not associated with increases in total cholesterol, low-density lipoprotein cholesterol, or triglycerides (+0.9, -1.7, -1.5 mg/dL lersivirine 500mg; -4.2, -4.6, -3.1 mg/dL 750mg; +15.5, +4.0, +10.6 mg/dL efavirenz).
Conclusion: Both lersivirine doses showed similar efficacy to efavirenz over 48 weeks in treatment-naïve patients and had different AE profiles compared with efavirenz.
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