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

• ClinicalTrials.gov Identifier: NCT02263326
• Recruitment Status: Completed
• First Posted: October 13, 2014
• Results First Posted: November 13, 2018
• Last Update Posted: October 14, 2019
• Sponsor: Babafemi Taiwo
• Collaborator: ViiV Healthcare
• Information provided by (Responsible Party): Babafemi Taiwo, Northwestern University

Study Description

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

Condition or disease	Intervention/treatment	Phase
HIV Infection	Drug: dolutegravir; Drug: lamivudine; Drug: Continue current antiretroviral regimen	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE) Study
• Study Start Date: December 2014
• Actual Primary Completion Date: July 2017
• Actual Study Completion Date: September 2017

Arms and Interventions

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 Name: TIVICAY, DTG; Drug: lamivudine; 300 mg tablet by mouth once daily for 48 weeks; Other Name: 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

Outcome Measures

Primary Outcome Measures :

1. Proportion of Participants With Treatment Failure [ Time Frame: 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 :

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

Other Outcome Measures:

1. Residual Viremia by HIV-1 Single-copy Assay [ Time Frame: 48 weeks ]
   Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis

Eligibility Criteria

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

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)

Contacts and Locations

Locations

United States, California

University of California San Diego

San Diego, California, United States

United States, Georgia

Emory University

Atlanta, Georgia, United States

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States

United States, New York

Cornell University

New York, New York, United States

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

Sponsors and Collaborators

Babafemi Taiwo

ViiV Healthcare

Investigators

• Principal Investigator: Babafemi Taiwo, MBBS; Northwestern University

  Study Documents (Full-Text)

Documents provided by Babafemi Taiwo, Northwestern University:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] June 25, 2015

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Babafemi Taiwo, Professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT02263326
• Other Study ID Numbers: ASPIRE
• First Posted: October 13, 2014
• Results First Posted: November 13, 2018
• Last Update Posted: October 14, 2019
• Last Verified: October 2019

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lamivudine; Dolutegravir; Anti-Retroviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents; HIV Integrase Inhibitors; Integrase Inhibitors