A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects (ING112276)

Inclusion Criteria:

• HIV-1 infected male or female adults at least 18 years of age. Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol);
• HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000copies/mL;
• CD4+ cell count greater than or equal to 200cells/mm3 (or higher as local guidelines dictate);
• ART-naive (less than or equal to 10 days of prior therapy with any antiretroviral agent). Any previous exposure to an HIV integrase inhibitor other than GSK1349572 will be exclusionary.
• No evidence of viral resistance to any antiretroviral drug indicative of primary transmitted resistance at screening;
• Able to understand and comply with protocol requirements;
• Able to provide written informed consent prior to screening;
• French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Note: Subjects starting abacavir as part of the NRTI backbone must have been screened and be negative for the HLA-B*5701 allele.

Exclusion Criteria:

• Any pre-existing or serious mental or physical disorder 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;
• Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives;
• History of clinically relevant pancreatitis or hepatitis within the previous 6 months, including HBsAg positive result. Asymptomatic HCV infection will not be exclusionary, however subject who will require HCV therapy during the trial should be excluded. Any subject with a history of liver cirrhosis with or without hepatitis viral co-infection will be excluded.
• Any condition which could interfere with the absorption, distribution, metabolism or excretion of the drug;
• Any acute or Grade 4 laboratory abnormality at screening;
• History of upper gastrointestinal bleed and/or subjects with active peptic ulcer disease;
• Estimated creatinine clearance <50 mL/min;
• Alanine aminotransferase (ALT) greater than or equal to 5 times ULN;
• Alanine aminotransferase (ALT) greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with >35% direct bilirubin);
• Lipase greater than or equal to 3xULN;
• Hemoglobin < 100 g/L(10 g/dL);
• History of allergy to the study drugs or their components or drugs of their class;
• Treatment with radiation therapy, cytotoxic chemotherapeutic agents, any agents with activity against HIV-1 or immunomodulators within 28 days prior to screening;
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to screening;
• History of protocol-defined cardiac diseases;
• Personal or family history of prolonged QT syndrome;
• Any clinically significant finding, as specified in the protocol, on electrocardiograph (ECG);
• Significant blood loss in excess of 500 mL within a 56 day period prior to screening visit;
• Immunization within 30 days prior to first dose of investigational product;
• French subjects: The subject has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study or the subject will participate simultaneously in another clinical study.