Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure

Phase 3

Completed

Interventions: Drug: Continue current antiretroviral regimen
Drug: dolutegravir
Drug: lamivudine

Brief 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

Detailed Description: 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

Recruitment & Eligibility

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

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)

Arm && Interventions

Group	Intervention	Description
Continue current ART regimen	Continue current antiretroviral regimen	Continue current DHHS recommended or alternative three-drug antiretroviral regimen
dolutegravir plus lamivudine	lamivudine	dolutegravir 50 mg plus lamivudine 300 mg once daily
dolutegravir plus lamivudine	dolutegravir	dolutegravir 50 mg plus lamivudine 300 mg once daily

Primary Outcome Measures

Name	Time	Method
Proportion of Participants With Treatment Failure	24 weeks	Proportion of participants with treatment failure (defined as virologic failure (HIV RNA \>50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen

Secondary Outcome Measures

Name	Time	Method
Change in LDL Cholesterol From Baseline to Week 48	Baseline and Week 48	Change in Low-density lipoprotein (LDL) cholesterol between arms will be presented in the attached statistical analysis table
Drug Resistance Associated Mutations	48 weeks	Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure
Change in Creatinine Clearance From Baseline to Week 48	Baseline and Week 48	Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table
Proportion of Participants With Virologic Success	48 weeks	Proportion of participants with virologic success (\<50 copies/mL) based on FDA snapshot definition
Change in CD4 Count From Baseline to Week 48	Baseline and 48 weeks	Change in CD4 count between arms will be presented in the attached statistical analysis table
Change in Total Cholesterol From Baseline to Week 48	Baseline and 48 weeks	Change in Total Cholesterol between arms will be presented in the attached statistical analysis table

Locations (7): University of California San Diego
🇺🇸
San Diego, California, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
The Ohio State University
🇺🇸
Columbus, Ohio, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
Cornell University
🇺🇸
New York, New York, United States