Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir

Study ING116529 is a multicenter, randomized, study with an initial 7 day placebo-controlled,
functional monotherapy phase to assess the antiviral activity and safety of a dolutegravir
(DTG, GSK1349572) containing regimen in HIV-1 infected, ART-experienced adults with
virological failure on an integrase inhibitor (INI) containing regimen.

Subjects must have evidence of genotypic resistance to raltegravir [RAL] or elvitegravir
[ELV] at Screening and documented current or historical genotypic or phenotypic resistance to
at least two other antiretroviral therapy drug classes.

The study is designed to provide an accurate measure of the intrinsic antiviral activity of
DTG 50mg twice daily versus placebo both administered with the current failing regimen in a
randomised double-blind phase to Day 8. This will be followed by an open label phase with all
subjects receiving DTG 50mg twice daily with an optimized background regimen (containing at
least one fully active drug) until subjects no longer derive clinical benefit or until DTG is
locally available. Thirty subjects will be randomized (1:1) to receive either DTG 50mg BID
(Arm A) or Placebo (Arm B) with the current failing regimen for 7 days (RAL or ELV should be
discontinued prior to dosing at Day 1). At Day 8, subjects from both arms will enter an open
label phase and receive open label DTG 50mg BID with an optimized background regimen
containing at least one fully active drug The primary analysis will be conducted after the
last subject enrolled has completed the randomised, double-blind phase at Day 8. Additional
analyses may be performed prior to study closure when all ongoing subjects transition to
locally available commercial DTG.

Inclusion Criteria:

- Screening plasma HIV-1 RNA ≥1000 copies/mL

- ART-experienced, INI-experienced, DTG naïve

- Current virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen

- The subject's HIV-1 shows genotypic resistance to RAL or ELV at Screening

- Subject has been on stable ART for at least one month prior to Screening and through
Day 1(with exceptions for ETV, EFV and NVP that can be interrupted within 14 days of
Day 1, see Exclusion Criterion)

- Documented resistance to at least one drug from each of two or more of any approved
classes of ART other than integrase inhibitors

- Be able to receive at least one fully active drug as part of the OBR from Day 8

- Women capable of becoming pregnant must use appropriate contraception during the study
(as defined by the protocol)

- Willing and able to understand and provide signed and dated written informed consent
prior to Screening.

Exclusion Criteria:

- Women who are pregnant or breast feeding

- An active AIDS-defining condition at Screening (except cutaneous Kaposi's sarcoma not
requiring systemic therapy or CD4+ <200c/mm3)

- Moderate to severe hepatic impairment as defined by Child-Pugh classification

- Anticipated need for HCV therapy during the first 24 weeks of the study

- Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal
bleed, with the exception of anal or rectal bleeding

- Allergy or intolerance to the study drugs or their components or drugs of their class

- Malignancy within the past 6 months

- Treatment with an HIV-1 therapeutic vaccine within 90 days of Screening

- Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any
immunomodulator within 28 days of Screening

- Treatment with any agent, other than licensed ART, with documented in vitro/vivo
activity against HIV-1 within 28 days of first dose of investigational product (with
the exception of entecavir if required for Hep B treatment)

- Treatment with etravirine, efavirenz, or nevirapine within 14 days of Day 1(etravirine
may be used if coadministered with lopinavir/ritonavir or darunavir/ritonavir)

- Treatment with tipranivir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir within
28 days prior to Screening

- Exposure to an experimental drug or vaccine within either 28 days, 5 half-lives of the
test agent, or twice the duration of the biological effect of the test agent, which
ever is longer, prior to the first dose of IP.

- Any acute or verified Grade 4 laboratory abnormality (with the exception of Grade 4
lipids) at Screening

- ALT> 5 times the upper limit of normal (ULN) at Screening

- ALT ≥ 3X ULN and bilirubin > 1.5 X ULN (with 35% direct bilirubin) at Screening