Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure

DESIGN HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic
failure and plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States
Department of Health and Human Services (DHHS) recommended or alternative three-drug
antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or
continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic
failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24

All subjects will undergo routine monitoring including plasma HIV-1 RNA, CD4/CD8 count,
hematology, chemistry and fasting lipids. Resistance testing will be done in all patients who
experience virologic failure. Single-copy HIV-1 assay will be done to quantify residual
viremia.

DURATION 48 weeks

SAMPLE SIZE 90 subjects

POPULATION HIV-1-infected men and women, 18 years and older, with CD4 nadir > 200 cells/mm3,
no baseline resistance, no history of virologic failure, and HIV RNA <50 copies/mL for at
least 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug
regimen

REGIMEN Subjects will be randomized (1:1) to:

Arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily OR Arm 2: Continue current DHHS
recommended or alternative three-drug antiretroviral regimen

Inclusion Criteria:

- HIV-1 Infection

- HIV-1 RNA <50 copies/mL on all measurements within 48 weeks prior to study entry while
on any DHHS recommended or alternative three-drug antiretroviral regimen. (A history
of switching for simplification and/or tolerability is allowed. At least two
measurements within the previous 48 weeks are required prior to study screening.)

- No history of virologic failure, defined as consecutive HIV RNA > 50 copies/mL after
12 months of initiating ART. An isolated (non-consecutive) HIV RNA > 50 copies/mL (but
less than 400 copies/mL) is permitted after 12 months of initiating ART but not in the
48-week window prior to study entry.

- Screening plasma HIV RNA < 20 copies/mL using the COBAS AmpliPrep/COBAS TaqMan HIV-1
Test V2.0, obtained within 45 days prior to study entry

- Nadir CD4 count >200 cells/mm

- Pretreatment genotype documenting no mutations in the protease or reverse
transcriptase genes

- No known resistance to integrase inhibitors

- Laboratory values obtained within 45 days prior to study entry:

ANC >750 Hemoglobin >10 g/dL Platelets >50,000 Calculated creatinine clearance (CrCl) >50
mL/min

- Negative serum or urine pregnancy test

- Men and women age greater or equal to 18 years.

- Ability to continue current regimen (i.e, have uninterrupted access)

- No evidence of chronic hepatitis B

Exclusion Criteria:

- Serious illness or AIDS-related complication within 21 days of screening requiring
systemic treatment and/or hospitalization

- Treatment within 30 days prior to study entry with immune modulators

- Vaccination within 7 days

- Active HCV treatment or anticipated need for treatment within study period. (HCV
infection alone is not exclusionary)

- Unstable liver disease or severe hepatic impairment

- Known allergy or hypersensitivity to DTG or lamivudine.

- Active drug or alcohol use or dependence that could interfere with adherence to study
requirements

- ALT (alanine aminotransferase) >5 x ULN (upper limit of normal) OR ALT >3 x ULN and
total bilirubin >1.5 x ULN (with 35% direct bilirubin)