Triumeq As an Integrase Single Tablet Regimen in People With HIV Who Inject Drugs (TAISTR)

A Prospective, Single Arm, Open-label 96 Week Observational Trial of the Tolerability, Adherence and Efficacy of a Dolutegravir/Abacavir/Lamivudine Single Tablet Regimen in HIV-1 Antibody Positive People Living With HIV With a History of Injection Drug Use Switching From Existing ART or Starting Treatment After Discontinuation of ART

The purpose of this study is to assess the tolerability, adherence and efficacy of single tablet dolutegravir/abacavir/lamivudine antiretroviral therapy in people living with HIV with a history of injection drug use (IDU) switching from existing antiretroviral therapy (ART) or starting treatment after discontinuation of ART.

Study Overview

• Status: Terminated
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Drug: dolutegravir/abacavir/lamivudine

Detailed Description

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) that supports once-daily dosing without the need for pharmacokinetic boosting and may be co-formulated with other antiretrovirals into a single-tablet regimen (STR). With people living with HIV with injection drug use (IDU) being more prone to unplanned antiretroviral therapy (ART) discontinuation and suboptimal adherence, DTG offers a high genetic barrier to resistance, a profile that reduces drug-drug interactions, with better tolerability and its availability as single tablet regimen (STR) combined with abacavir and lamivudine (ABC/3TC) is likely to improve adherence.

The aims of this study include:

• To assess tolerability through self-reported adverse effects and directed symptom questionnaire
• To determine change in number and severity of reported ART-related adverse effects from baseline to week 48 and 96
• To determine change in health-related quality of life (HRQOL) from baseline to week 48 and 96
• To determine change in frailty score from baseline to week 48 and 96
• To determine the percentage of subject with unscheduled ART discontinuations/ interruptions over 96 weeks
• To determine the estimated number of weeks of missed ART over 48 and 96 weeks of follow-up
• To determine change from baseline of medication possession ratio (MPR) at 48 and 96 weeks or adherence score as measured by an antiretroviral therapy medication self-report form at the same time points
• To determine the percentage of subjects with HIV RNA<40 copies/mL at 96 weeks
• To determine change in genotypic resistance profiles in subjects experiencing virological failure
• To determine change in CD4+ T-cell counts through 96 weeks
• To determine change in bone mineral density through 96 weeks
• To determine the number of subjects with any adverse and any serious adverse events (SAE) from baseline to week 96
• To determine the number of subject with Grade 1 to 4 laboratory abnormalities from baseline to week 96

This is a prospective, single arm, open-label 96 weeks clinical trial. Study subjects will be followed for 96 weeks post enrolment, with regular clinical evaluations, laboratory evaluations, safety and adherence assessment, quality of life and bone mineral density (BMD) measured at regular intervals.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, 7
    • Mater Misericordiae University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HIV-infected adults (≥18 years of age) with a history of IDU as the principal HIV transmission risk factor or with current or recent (past 12 months) history of IDU
• Either currently receiving an antiretroviral regimen but experiencing adherence or tolerability issues on current ART or restarting ART after an unscheduled treatment interruption
• Willing to switch current ART regimen
• No documented viral resistance to currently licensed HIV-1 integrase inhibitors, abacavir and lamivudine based either on previous HIV-1 genotypic resistance testing or in the judgment of the study investigators
• Integrase inhibitor naïve (defined as no-prior exposure to any INSTI)
• Documented negative HLAB*5701 allele

Exclusion Criteria:

• Subjects with active hepatitis B infection (defined as hepatitis B surface antigen (sAg) positive)
• Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification;
• Chronic renal failure estimated by glomerular filtration rate (eGFR) <60mls/min/1.73m2 at screening using the abbreviated Modification of Diet in Renal Disease (MDRD) equation
• Any active illness (including AIDS-defining illness) which in the opinion of the investigator would prevent the subject from completing all study assessments
• Female subjects who are pregnant, breastfeeding or planning future pregnancies or unwilling to take measures to avoid pregnancy for the study duration
• Any grade 4 laboratory abnormalities
• Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification
• Subjects weighing less than 40 kilograms and those are likely to require a Triumeq dose adjustment
• History or presence of allergy to the study drug or their components
• A diagnosis of cancer under current active chemotherapy or radiotherapy or having received chemotherapy or radiotherapy for a diagnosis of cancer within the previous 21 days prior to screening
• Subjects with a documented HLAB*5701 positive test on archived or screening bloods
• Concurrent use of any contraindicated medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dolutegravir/abacavir/lamivudine; All study subjects will receive triumeq (600 mg abacavir, 50 mg dolutegravir and 300 mg lamivudine) single tablet that will be taken orally, once daily, during 96 weeks	Drug: dolutegravir/abacavir/lamivudine; 600 mg abacavir, 50 mg dolutegravir and 300 mg lamivudine single tablet taken orally, once daily, during 96 weeks; Other Names: Triumeq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tolerability as assessed by the number of subjects with treatment-related adverse events measured using a self-reported form and directed symptoms questionnaire	Measured through 96 weeks
Proportion of subjects with unscheduled discontinuation of study treatment	Measured through 96 weeks
Change in medication possession ratio (MPR) at 48 weeks or adherence score as measured by an antiretroviral therapy medication self-report form	Measured through 48 weeks
Proportion of subjects with HIV RNA<40 cps/ml at 48 weeks	Measured through 48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in number and severity of ART-related adverse effects	Measured through 48 weeks; 96 weeks
Change in health-related quality of life (HRQOL)	Measured through 48 weeks; 96 weeks
Change in frailty score	Measured through 48 weeks; 96 weeks
Estimated number of weeks of missed ART	Measured through 48 weeks; 96 weeks
Change from baseline in medication possession ratio (MPR) at 96 weeks or adherence score as measured by an antiretroviral therapy medication self-report form	Measured through 96 weeks
Proportion of subjects with HIV RNA<40 copies/mL	At 96 weeks
Change in the number of drug resistant mutations in subjects experiencing virological failure	Measured through 96 weeks
Change in bone mineral density	Measured through 96 weeks
Number of subjects with any adverse and any serious adverse events (SAE) and/or grade 1 to 4 laboratory abnormalities	Measured through 96 weeks
Change in CD4+ T-cell count	Measured through 96 weeks

Collaborators and Investigators

• Sponsor: University College Dublin
• Collaborators: ViiV Healthcare; Mater Misericordiae University Hospital
• Investigators: Principal Investigator: Patrick Mallon, MB BCh, PhD, FRCPI, University College Dublin

Publications and helpful links

General Publications

• Cohn SE, Jiang H, McCutchan JA, Koletar SL, Murphy RL, Robertson KR, de St Maurice AM, Currier JS, Williams PL. Association of ongoing drug and alcohol use with non-adherence to antiretroviral therapy and higher risk of AIDS and death: results from ACTG 362. AIDS Care. 2011 Jun;23(6):775-85. doi: 10.1080/09540121.2010.525617.
• Meemken L, Hanhoff N, Tseng A, Christensen S, Gillessen A. Drug-Drug Interactions With Antiviral Agents in People Who Inject Drugs Requiring Substitution Therapy. Ann Pharmacother. 2015 Jul;49(7):796-807. doi: 10.1177/1060028015581848. Epub 2015 Apr 22.

Helpful Links

• Centre for Experimental Host Pathogen Research

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: January 8, 2016
• First Submitted That Met QC Criteria: January 15, 2016
• First Posted (Estimated): January 20, 2016

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Adherence; Efficacy; Tolerability; Human Immunodeficiency Virus; Dolutegravir; Injection drug use; Single-tablet antiretroviral treatment
• 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; Immune System Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Lamivudine; Dolutegravir; Abacavir
• Other Study ID Numbers: TAISTR_2016