6-fold reduction in susceptibility [1–5]. A median 1.8-fold reduction in susceptibility BI 6727 in vivo to ATC has been observed in a study of HIV-1

isolates containing five TAMs in the 41, 215 pathway and a median 1.3-fold reduction in susceptibility in isolates containing five TAMs in the 67, 70, 219 pathway [3]. ATC has shown promising antiviral activity when given as monotherapy over 10 days in treatment-naïve HIV-1-infected patients [6]. In a double-blind, randomized Phase II study of 63 patients, reductions in viral load were observed in patients receiving one of four different total daily doses of ATC (given as six dosing regimens), with all dose groups having a statistically significant decrease in plasma HIV-1 RNA levels from baseline relative to placebo after 7 days of treatment. In addition, ATC did not select for any particular mutation during the 10-day treatment period. The aim of this study was to evaluate and compare the efficacy and safety of two doses of ATC in HIV-1-infected patients who were treatment-experienced and harbouring the M184V mutation, with or without additional TAMs. Patients enrolling in this study were failing their current 3TC- or FTC-containing regimen, with limited remaining

treatment options. The first part of the study (to day 21) evaluated the antiviral effect of two doses of ATC by replacement this website of the 3TC/FTC in the patients’ existing treatment regimen with one of two doses of ATC or with (continued) 3TC. The 3-week duration of this period of treatment with ATC allowed assessment of the activity of ATC in

the background of a failing treatment regimen while limiting the potential for the development of resistance mutations. At day 21, the background antiretroviral therapy (ART) could be optimized according to the patient’s genotype at screening and treatment with ATC or 3TC continued to week 24. Reported here are the primary endpoints of the study, the efficacy and safety results at day 21. SB-3CT This was a Phase IIb randomized, double-blind, dose-ranging, multicentre study conducted in Argentina and Australia. The study was conducted according to International Conference on Harmonisation (ICH) Good Clinical Practice Guidelines and was approved by the appropriate local Ethics Committees. All patients gave written informed consent before participating in the study. Eligible patients had a documented laboratory diagnosis of HIV-1 infection [positive enzyme-linked immunosorbent assay (ELISA) HIV-1 antibody test confirmed by western blot, p24 assay, HIV-1 RNA or culture] with plasma HIV-1 RNA levels≥2000 copies/mL (using the Ultrasensitive COBAS Amplicor® HIV-1 Monitor™ version 1.5, Roche Molecular Systems Inc., Branchburg, NJ, USA) and presence of the M184V mutation in the HIV-1 reverse transcriptase at screening by genotype assay.