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

Study Description

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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

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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

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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

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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

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Ages Eligible for Study:	18 Years to 65 Years (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

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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

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Responsible Party:	Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier:	NCT02513147 History of Changes
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; Darunavir; Atazanavir Sulfate; 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