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

Human Immunodeficiency Virus Clinical Trial

— TAISTR  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02659761
• Other study ID #: TAISTR_2016
• Status: Terminated
• Phase: Phase 4
• Start date: November 2016
• Est. completion date: September 2021

Study information

• Verified date: May 2024
• Source: University College Dublin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 33
• Est. completion date: September 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes

Intervention

Drug:
• dolutegravir/abacavir/lamivudine
600 mg abacavir, 50 mg dolutegravir and 300 mg lamivudine single tablet taken orally, once daily, during 96 weeks

Locations

Country	Name	City	State
Ireland	Mater Misericordiae University Hospital	Dublin

Sponsors (3)

Lead Sponsor	Collaborator
University College Dublin	Mater Misericordiae University Hospital, ViiV Healthcare

Country where clinical trial is conducted

Ireland, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Proportion of subjects with unscheduled discontinuation of study treatment		Measured through 96 weeks
Primary	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
Primary	Proportion of subjects with HIV RNA<40 cps/ml at 48 weeks		Measured through 48 weeks
Secondary	Change in number and severity of ART-related adverse effects		Measured through 48 weeks; 96 weeks
Secondary	Change in health-related quality of life (HRQOL)		Measured through 48 weeks; 96 weeks
Secondary	Change in frailty score		Measured through 48 weeks; 96 weeks
Secondary	Estimated number of weeks of missed ART		Measured through 48 weeks; 96 weeks
Secondary	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
Secondary	Proportion of subjects with HIV RNA<40 copies/mL		At 96 weeks
Secondary	Change in the number of drug resistant mutations in subjects experiencing virological failure		Measured through 96 weeks
Secondary	Change in bone mineral density		Measured through 96 weeks
Secondary	Number of subjects with any adverse and any serious adverse events (SAE) and/or grade 1 to 4 laboratory abnormalities		Measured through 96 weeks
Secondary	Change in CD4+ T-cell count		Measured through 96 weeks

External Links

•   Centre for Experimental Host Pathogen Research