Clinical trial NCT02263326: Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure
Official title: Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infection
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: ViiV Healthcare
First posted: 2014-10-13
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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)

Primary outcomes:
measure: Proportion of Participants With Treatment Failure
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of Participants With Virologic Success
timeFrame: 48 weeks
measure: Change in CD4 Count From Baseline to Week 48
timeFrame: Baseline and 48 weeks
measure: Change in Total Cholesterol From Baseline to Week 48
timeFrame: Baseline and 48 weeks
measure: Change in LDL Cholesterol From Baseline to Week 48
timeFrame: Baseline and Week 48
measure: Change in Creatinine Clearance From Baseline to Week 48
timeFrame: Baseline and Week 48
measure: Drug Resistance Associated Mutations
timeFrame: 48 weeks
Other outcomes:
measure: Residual Viremia by HIV-1 Single-copy Assay
timeFrame: 48 weeks
Locations:
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: New York
country: United States
facility: Cornell University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
affiliation: Northwestern University
name: Babafemi Taiwo, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taiwo BO, Marconi VC, Berzins B, Moser CB, Nyaku AN, Fichtenbaum CJ, Benson CA, Wilkin T, Koletar SL, Colasanti J, Acosta EP, Li JZ, Sax PE. Dolutegravir Plus Lamivudine Maintains Human Immunodeficiency Virus-1 Suppression Through Week 48 in a Pilot Randomized Trial. Clin Infect Dis. 2018 May 17;66(11):1794-1797. doi: 10.1093/cid/cix1131.