Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE)

Babafemi Taiwo

Status and phase

Completed

Phase 3

Conditions

HIV Infection

Treatments

Drug: lamivudine

Drug: Continue current antiretroviral regimen

Drug: dolutegravir

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02263326

ASPIRE

Details and patient eligibility

About

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

Full 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

Enrollment

89 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)