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

• ClinicalTrials.gov Identifier: NCT02513147
• Recruitment Status: Completed
• First Posted: July 31, 2015
• Last Update Posted: June 14, 2017
• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: University Hospital, Ghent; IrsiCaixa
• Information provided by (Responsible Party): Hospital Universitari Vall d'Hebron Research Institute

Study Description

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).

Condition or disease	Intervention/treatment	Phase
HIV-1	Drug: Dolutegravir; Drug: PI; Drug: 2 NRTI	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: HIV Reservoir Dynamics After Switching to Dolutegravir in Patients With Two NRTI and a Protease Inhibitor Based Regimen. A Phase IV Open Randomized Trial
• Study Start Date: June 2015
• Actual Primary Completion Date: November 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: 2 NRTI+ Dolutegravir; 22 patients will be treated with 2 NRTI+Dolutegravir 50 mg during 24 weeks	Drug: Dolutegravir; Drug: 2 NRTI
Active Comparator: 2 NRTI + PI; 22 patients will be treated with 2 NRTI + PI during 24 weeks	Drug: 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; Other Name: Fosamprenavir, atazanavir, lopinavir or darunavir; Drug: 2 NRTI; Other Name: 2NRTI

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 1 week ]
2. 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 [ Time Frame: 2 weeks ]
3. 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 [ Time Frame: 4 weeks ]
4. 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 [ Time Frame: 12 weeks ]
5. 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 [ Time Frame: 24 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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:

  1. 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.

  2. 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.

Exclusion Criteria:

• 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

Contacts and Locations

Locations

Spain

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Sponsors and Collaborators

Hospital Universitari Vall d'Hebron Research Institute

University Hospital, Ghent

IrsiCaixa

More Information

• Responsible Party: Hospital Universitari Vall d'Hebron Research Institute
• ClinicalTrials.gov Identifier: NCT02513147
• Other Study ID Numbers: INDOOR
• First Posted: July 31, 2015
• Last Update Posted: June 14, 2017
• Last Verified: June 2017

Additional relevant MeSH terms:

Lopinavir; Atazanavir Sulfate; Darunavir; Fosamprenavir; Dolutegravir; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors