A Study of the Pharmacokinetics and Antiviral Activity of Dolutegravir in the Central Nervous System in HIV-1 Infected ART-naive Subjects

Inclusion Criteria:

• HIV-1 infected adults at least 18 years of age. Females are eligible to enter and participate in the study if she is (1) of non-childbearing potential or (2) of childbearing potential with a negative pregnancy test at Screening and Day 1 and agrees to use protocol-defined methods of birthcontrol while on the study.
• HIV-1 infection as documented by Screening plasma HIV-1 RNA greater than or equal to 5000 copies/mL
• CD4+ cell count greater than or equal to 200 cells/mm3
• Antiretroviral-naive (less than or equal to 10 days of prior therapy with any antiretroviral agent following diagnosis of HIV-1 infection)
• Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening
• Documentation that the subject has been screened for, and is negative for the HLA-B*5701 allele
• Is willing to undergo serial lumbar punctures

Exclusion Criteria:

• Relative or absolute contraindication to lumbar puncture, such as current coagulopathy, thrombocytopenia (platelets less than 50,000/microliter), hemophilia, or use of anticoagulant medication
• Moderate or severe cognitive impairment
• Women who are pregnant or breastfeeding
• Any evidence of an active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy or historic CD4+ cell levels less than 200cells/mm3
• Subjects with any degree of hepatic impairment
• Positive for Hepatitis B at screening (+HbsAg), or an anticipated need for Hepatitis C virus (HCV) therapy during the study
• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class
• History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject
• Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
• Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any immunomodulators that alter immune responses
• Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 in vitro within 28 days of first dose of IP
• Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP
• Any evidence of primary viral resistance based on the presence of any major resistance-associated mutation in the Screening result or, if known, any historical resistance test result. Note: retests of Screening genotypes are not allowed
• Any verified Grade 4 laboratory abnormality (a single repeat test is allowed during the Screening period to verify a result). Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound is exclusionary
• Alanine aminotransferase (ALT) greater than 5 times the upper limit of normal (ULN)
• ALT greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with greater than 35% direct bilirubin)
• Subject has creatinine clearance of less than 50 mL/min via Cockroft-Gault method