Dolutegravir Impact on Residual Replication

• Status: Completed
• Trial end date: 2017-09-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Melbourne
• Collaborators: The Alfred; ViiV Healthcare
• Treatments: Dolutegravir

Criteria

Inclusion Criteria:

• 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:

Exclusion Criteria:

• 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

• Women of Child Bearing Potential (WOCBP) unwilling or unable to use an acceptable method of contraception to avoid pregnancy as specified in the inclusion criteria

• Unable or unwilling to adhere to protocol procedures

• The following laboratory values within 3 weeks before starting the investigational drug (lab tests may be repeated to obtain acceptable values before failure at screening is concluded)

• Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)

• Serum total bilirubin ≥1.5 x ULN

• eGFR <50 mL/min

• Haemoglobin <11.0 g/dL