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

Vall d'Hebron University Hospital (HUVH)

Status and phase: Completed; Phase 4

Conditions: HIV-1

Treatments: Drug: 2 NRTI; Drug: PI; Drug: Dolutegravir

Study type: Interventional

Funder types: Other

Identifiers

NCT02513147

INDOOR

Details and patient eligibility

About

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).

Enrollment: 44 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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44 participants in 2 patient groups

2 NRTI+ Dolutegravir

Experimental group

Description:

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

Treatment:

Drug: 2 NRTI

Drug: 2 NRTI

Drug: Dolutegravir

2 NRTI + PI

Active Comparator group

Description:

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

Treatment:

Drug: 2 NRTI

Drug: 2 NRTI

Drug: PI