a dose ranging study of gw640385 boosted with ritonavir (rtv) in comparison to a rtv-boosted protease inhibitor (pi) in hiv-1 infected pi-experienced adults

Conditions: Infection, Human Immunodeficiency Virus I; HIV-1 Infection

Summary: this is a two phase study (randomised and non-randomised phase). the randomised phase will initially examine 4 blinded doses of gw640385 boosted with rtv (with continuation of current background therapy) in comparison to an ongoing, open-labeled rtv-boosted protease inhibitor (pi) regimen for 15 days. at the day 15 visit, all subjects will optimize background therapy. additionally, subjects receiving the lowest dose of gw640385 will be re-randomised to one of the higher doses and subjects in the control arm will receive a new rtv-boosted pi based on resistance testing at screening. subjects will remain in the randomized phase on one of these 4 continuing treatment arms for at least 48 weeks. an interim analysis will occur during the randomised phase to select for a dose of gw640385 to evaluate further in phase iii studies. after dose selection subjects will move to the non-randomised phase of the study. in the non-randomised phase subjects who are receiving gw640385 will be assigned to final selected dose for assessment of long term safety, tolerability, pharmacokinetics, and antiviral activity.

a phase iib, randomized, multicenter, parallel group study to evaluate the short-term safety, pk and antiviral activity of four dosing regimens of gw640385/rtv therapy compared to open-label current protease inhibitor (pi) therapy in hiv-1, pi-experienced adults for 2 wks with long-term evaluation (\>48 wks) of safety, pk and antiviral activity of selected gw640385/rtv dosing regimen(s) vs. a rtv-boosted, pi containing regimen

Eligibility criteria:
inclusion criteria: * 18+ years of age (or =16 years of age for non-eu countries, according to local requirements). * hiv-1 infected subjects. * females must be of either non-childbearing potential or have a negative pregnancy test at screening and agree to use a protocol approved method of contraception. * plasma hiv-1 rna (viral load) =1,000 copies/ml at screening. * evidence of at least 2 multi-pi resistant mutations at screening or within 3 months of screening. * subjects must have been receiving the same anti-hiv medicines that they are on currently for at least 8 weeks prior to screening; these anti-hiv medicines will include a single protease inhibitor (pi) in combination with a low dose of ritonavir (i.e., a ritonavir-boosted pi). however, the current pi cannot be tipranavir. * able to understand and follow protocol requirements, instructions and protocol-stated restrictions. * be willing and able to provide signed and dated written informed consent prior to study entry. exclusion criteria: * subjects cannot change their anti-hiv medicines between screening and day 1 visit. * subjects can not be receiving dual ritonavir-boosted pis, non-nucleoside reverse transcriptase inhibitors (nnrtis) or tipranavir at screening. * active cdc class c disease at screening. * pregnant or breastfeeding women. * protocol-specified laboratory abnormalities at screening.

Keywords: treatment-experienced rtv protease inhibitor ritonavir gw640385 hiv-1