Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: dolutegravir; lamivudine; Continue current antiretroviral regimen
Intervention description: 50 mg tablet by mouth once daily for 48 weeks; 300 mg tablet by mouth once daily for 48 weeks; Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Intervention MeSH terms: Lamivudine; Dolutegravir; Anti-Retroviral Agents
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 89.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        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)