HIV Reservoir Dynamics After Switching to Dolutegravir in Patients on a PI and 2 NRTI Based Regimen

NCT02513147 | Completed Phase 4

• 1 other identifier: INDOOR
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess changes in viral reservoir after changing IP/r to dolutegravir in HIV-1 infected patients maintaining undetectable viral load on Antiretroviral Therapy (ART).

Conditions

HIV-1

Outcome Measures

Primary Outcomes (5)

• Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 1 of the study compared to day 0

  1 week

• Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 2 of the study compared to day 0

  2 weeks

• Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 4 of the study compared to day 0

  4 weeks

• Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 12 of the study compared to day 0

  12 weeks

• Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 24 of the study compared to day 0

  24 weeks

Study Arms (2)

2 NRTI+ Dolutegravir

EXPERIMENTAL

22 patients will be treated with 2 NRTI+Dolutegravir 50 mg during 24 weeks

Drug: Dolutegravir; Drug: 2 NRTI

2 NRTI + PI

ACTIVE COMPARATOR

22 patients will be treated with 2 NRTI + PI during 24 weeks

Drug: PI; Drug: 2 NRTI

Interventions

Dolutegravir DRUG

2 NRTI+ Dolutegravir

PI DRUG

(Fosamprenavir, atazanavir, lopinavir or darunavir) boosted with 100 mg of ritonavir, or atazanavir (400 mg / d) not boosted with ritonavir,if the 2 NRTIs are abacavir + Lamivudine

Also known as: Fosamprenavir, atazanavir, lopinavir or darunavir

2 NRTI + PI

2 NRTI DRUG

2 NRTI+ Dolutegravir

Eligibility Criteria

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

You may qualify if:

• Adult patients infected with HIV-1
• HIV RNA \<50 copies / mL for ≥ 1 year with stable ART regimen (≥ 3 months) based on 2 NRTI and PI (Fosamprenavir, atazanavir, lopinavir or darunavir) boosted with 100 mg of ritonavir, or atazanavir (400 mg / d) not boosted with ritonavir, if the 2 NRTIs are abacavir + Lamivudine
• CD4 + lymphocytes \> 200 / mm3
• Signature of voluntary informed consent
• A woman may be eligible to enter and participate in the study if:
• No reproductive potential-defined as post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of getting pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy.
• It is in childbearing age with a negative pregnancy test on the day of screening and on Day 1 and agrees to use one of the following contraceptive methods to prevent pregnancy:
• Complete abstinence from penis-vaginal from 2 weeks prior to administration of investigational product, throughout the study, and for at least 2 weeks after discontinuation of all study drugs;
• Double barrier method (male / spermicidal condom, male condom / diaphragm, diaphragm / spermicide);
• Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year (not all IUDs meet this criterion)
• Male sterilization confirmed before the entry of the female subject in the study, and that this man is the only sexual partner for women
• Approved hormonal contraception
• Any other method with published data show that the expected failure rate is \<1% per year.

You may not qualify if:

• Prior virologic failure with an integrase inhibitor
• Acquired Immune Deficiency Syndrome (AIDS)-defining illness in the last 48 weeks
• Glomerular filtration rate \<50 mL / min, estimated by Chronic Kidney Disease Epidemiology (CKD-EPI) formula
• Alanine aminotransferase (ALT) ≥5 times the Upper Limit Normal (ULN) or ALT ≥3 X ULN and total bilirubin ≥1,5 ULN (with\> 35% direct bilirubin) and / or unstable liver disease (with the presence of ascites, hepatic encephalopathy, hypoalbuminemia, esophageal varices or persistent jaundice) or known biliary disorders excluded Gilbert syndrome or asymptomatic lithiasis) .
• Positive for hepatitis B (HBsAg +) or need for Hepatitis C Virus (HCV) treatment during the study .
• Subjects with severe hepatic impairment (Child Pugh Class C).
• Patients unable to understand the study protocol or any other condition that in the investigator's opinion could jeopardize compliance with the protocol
• Pregnant or breast-feeding
• History or presence of allergy to any of the study drugs or their components

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead
• University Hospital, Ghent: collaborator
• IrsiCaixa: collaborator

Study Sites (1)

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

MeSH Terms

Interventions

dolutegravir; fosamprenavir; Atazanavir Sulfate; Lopinavir; Darunavir

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Pyrimidinones; Pyrimidines; Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2015
• First Posted: July 31, 2015
• Study Start: June 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: June 14, 2017

Record last verified: 2017-06

Locations

ES (1)