A Pilot Study Assessing the Integrase Inhibitor GSK1349572 in HIV-infected Persons With Virus Resistant to Raltegravir

Inclusion Criteria:

• HIV-1 infected male or female adults at least 18 years of age with a plasma HIV-1 RNA > 1,000 copies/mL at study entry. Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
• ART-experienced (defined as on stable ART for at least the last 2 months) and is either currently experiencing virologic failure to RAL or experienced virologic failure to RAL > 8 weeks prior to Screening
• Must have documented RAL genotypic resistance on study entry genotype
• Must have documented genotypic or phenotypic resistance to at least one drug from each of three or more of all approved classes of ART
• For Cohort II, Subjects MUST be able to receive at least one fully active drug as part of the Day 11 optimised background regimen
• Willing and able to understand and provide signed and dated written informed consent prior to screening

Exclusion Criteria:

• Any pre-existing mental, physical, or substance abuse disorder which, which could compromise ability to comply with the protocol or compromise subject safety
• Women who are pregnant or breastfeeding
• An active AIDS-defining condition at the screening visit
• Currently take and/or anticipated need for EFV, NVP, FPV/RTV or TPV/RTV during the study
• Treatment with any of the following medications within 15 days of starting study drug, or anticipated to need, during the course of the study: Etravirine (unless co-administered with LPV/RTV or DRV/RTV), rifampin, rifabutin, phenytoin, phenobarbital, barbiturates, glucocorticoids, modafinil, oxcarbazepine, pioglitazone, troglitazone, carbamazepine, St. Johns wort
• Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives
• History of ongoing or clinically relevant pancreatitis or hepatitis within the previous 6 months
• Expected to require treatment for HCV infection during the first 24 weeks of the study
• Evidence of cirrhosis with or without hepatitis viral co-infection
• History of upper gastrointestinal bleed and/or active peptic ulcer disease
• Screening haemoglobin <10g/dL (100g/L)
• Subject suffers from a serious medical condition which could compromise the safety of the subject.
• Any condition that could interfere with the absorption, distribution, metabolism or excretion of the drug or render the subject unable to take oral medication
• Screening lipase 3 times the upper limit of normal (ULN)
• Any acute or Grade 4 laboratory abnormality at screening
• Screening alanine aminotransferase (ALT) >5xULN
• Screening ALT 3xULN and bilirubin 1.5xULN (with 35% direct bilirubin)
• Personal or family history of prolonged QT syndrome.
• Any clinically significant finding, as specified in the protocol, on screening or baseline electrocardiograph (ECG)
• History of allergy to the study drugs or their components or drugs of their class
• Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or future need of treatment with these agents during the study
• Treatment with immunomodulators within 28 days prior to screening or subject has received an HIV-1 vaccine within 90 days prior to screening