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

Phase 4

Completed

• Conditions: HIV-1
• Interventions: Drug: PI; Drug: Dolutegravir; Drug: 2 NRTI

• Registration Number: NCT02513147
• Lead Sponsor: Hospital Universitari Vall d'Hebron Research Institute

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-07-28
• Study First Submitted QC: 2015-07-30
• Study First Posted: 2015-07-31
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-13
• Last Update Posted: 2017-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2 NRTI+ Dolutegravir	2 NRTI	22 patients will be treated with 2 NRTI+Dolutegravir 50 mg during 24 weeks
2 NRTI + PI	PI	22 patients will be treated with 2 NRTI + PI during 24 weeks
2 NRTI + PI	2 NRTI	22 patients will be treated with 2 NRTI + PI during 24 weeks
2 NRTI+ Dolutegravir	Dolutegravir	22 patients will be treated with 2 NRTI+Dolutegravir 50 mg during 24 weeks

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain