Dolutegravir Impact on Residual Replication

NCT02500446 | Completed Phase 4

• 1 other identifier: DIORR_20150306
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Several studies have suggested that despite suppressive combination antiretroviral therapy (ART) in people who are HIV-positive, in some individuals there may be on-going viral replication. Clarifying the extent of on-going viral replication on ART is important for the development of HIV-1 curative strategies and for reducing HIV-1 associated immune activation. The investigators hypothesize that treatment intensification with dolutegravir will inhibit residual virus replication in HIV-1 infected patients on ART. The primary objective of this study is to determine the effects of dolutegravir intensification on residual virus replication in circulating cluster of differentiation 4 (CD4+) T cells.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• Level of residual HIV replication in circulating CD4+ T cells

  Change in the level of 2-LTR circles as measured by polymerase chain reaction (PCR) in the dolutegravir arm versus the placebo arm after 7 days of treatment

  day 7 of treatment

Secondary Outcomes (4)

• Level of Human Leukocyte Antigen D-related (HLA-DR)

  time points to day 84 (28 days after treatment)

• Level of Programmed cell death-1 receptor (PD-1)

  time points to day 84 (28 days after treatment)

• Level of Cluster of Differentiation 38 (CD-38)

  time points to day 84 (28 days after treatment)

• Level of residual HIV replication in circulating CD4+ T cells in a protease inhibitor -containing regimen

  time points up to day 84 (28 days after treatment)

Study Arms (2)

Intensification

ACTIVE COMPARATOR

Oral dolutegravir 50 mg once daily for 8 weeks added to their current ART regimen.

Drug: dolutegravir

Placebo

PLACEBO COMPARATOR

Oral placebo once daily for 8 weeks added to their current ART regimen.

Other: Placebo

Interventions

dolutegravir DRUG

Each film-coated tablet contains dolutegravir sodium equivalent to 50 mg dolutegravir.

Also known as: Tivicay®

Intensification

Placebo OTHER

A film-coated tablet identical in appearance to the active drug tablet but not containing any dolutegravir or any other active ingredient

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented HIV-1 infection
• Minimum age 18 years
• Receiving combination ART (at least 3 agents) for at least 3 years. Twenty of the 40 study participants will be on a PI-based ART regimen.
• HIV-1 plasma RNA \<50 copies/mL for \>3 years and \<20 copies/mL at screening.
• Two CD4+ T cell counts \>350 cells/μL in the 24 months prior to screening
• Able to give informed consent
• A female, may be eligible to enter and participate in the study if she:
• Is of non-child-bearing potential OR
• Is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the study protocol-specified methods of contraception to avoid pregnancy:

You may not qualify if:

• Known hypersensitivity to DTG or to any of the excipients
• Current use of dofetilide, pilsicainide or metformin
• Current use of etravirine except when etravirine is co-administered with atazanavir/ritonavir, lopinavir/ritonavir or darunavir/ritonavir
• Current or prior use of any integrase inhibitor
• Previous use of histone deacetylase inhibitors or other latency reversing agents
• Any significant acute medical illness requiring hospitalization within preceding 8 weeks
• Significant renal disease (eGFR \<50 milliliters per min)
• Hepatitis C co-infection (Individuals with prior hepatitis C infection that is now cleared are eligible for enrolment)
• Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Receipt of immunomodulating agents (excluding immunization) or systemic chemotherapeutic agents within 28 days prior to study entry
• Patients who intend to modify their ART regimen within the study period
• Current or recent gastrointestinal disease or surgery that may impact the absorption of the investigational drug
• Active alcohol or substance use that in the opinion of the investigator will prevent adequate compliance with study procedures
• Currently pregnant, breastfeeding or unwilling to use barrier contraception

Sponsors & Collaborators

• University of Melbourne: lead
• The Alfred: collaborator
• ViiV Healthcare: collaborator

Study Sites (2)

Melbourne Sexual Health Centre

Carlton, Victoria, 3053, Australia

Location

Alfred Hospital

Prahran, Victoria, 3010, Australia

Location

Related Publications (1)

• Rasmussen TA, McMahon JH, Chang JJ, Audsley J, Rhodes A, Tennakoon S, Dantanarayana A, Spelman T, Schmidt T, Kent SJ, Morcilla V, Palmer S, Elliott JH, Lewin SR. The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial. Lancet HIV. 2018 May;5(5):e221-e230. doi: 10.1016/S2352-3018(18)30040-7. Epub 2018 Apr 8.

  PMID: 29643011 DERIVED

MeSH Terms

Interventions

dolutegravir

Study Officials

• Sharon Lewin

  Doherty Institute for Immunity and Infection

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Doherty Institute

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 16, 2015
• Study Start: September 28, 2015
• Primary Completion: September 16, 2016
• Study Completion: September 30, 2017
• Last Updated: November 20, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)