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

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

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

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: dolutegravir; Drug: lamivudine; Drug: Continue current antiretroviral regimen

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

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States
      • University of California San Diego
  • Georgia
    • Atlanta, Georgia, United States
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States
      • Brigham and Women's Hospital
  • New York
    • New York, New York, United States
      • Cornell University
  • Ohio
    • Cincinnati, Ohio, United States
      • University of Cincinnati
    • Columbus, Ohio, United States
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dolutegravir plus lamivudine; dolutegravir 50 mg plus lamivudine 300 mg once daily	Drug: dolutegravir; 50 mg tablet by mouth once daily for 48 weeks; Other Names: TIVICAY, DTG; Drug: lamivudine; 300 mg tablet by mouth once daily for 48 weeks; Other Names: EPIVIR, 3TC
Active Comparator: Continue current ART regimen; Continue current DHHS recommended or alternative three-drug antiretroviral regimen	Drug: Continue current antiretroviral regimen; Continue current DHHS recommended or alternative three-drug antiretroviral regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Treatment Failure	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	24 weeks

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual Viremia by HIV-1 Single-copy Assay	Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis	48 weeks

Collaborators and Investigators

• Sponsor: Babafemi Taiwo
• Collaborators: ViiV Healthcare
• Investigators: Principal Investigator: Babafemi Taiwo, MBBS, Northwestern University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: October 6, 2014
• First Submitted That Met QC Criteria: October 8, 2014
• First Posted (Estimate): October 13, 2014

Study Record Updates

• Last Update Posted (Actual): October 14, 2019
• Last Update Submitted That Met QC Criteria: October 10, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Lamivudine; Anti-Retroviral Agents; Dolutegravir
• Other Study ID Numbers: ASPIRE