Clinical trial NCT02513147: HIV Reservoir Dynamics After Switching to Dolutegravir in Patients on a PI and 2 NRTI Based Regimen
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-1
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: IrsiCaixa
First posted: 2015-07-31
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 1 week
measure: 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
timeFrame: 2 weeks
measure: 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
timeFrame: 4 weeks
measure: 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
timeFrame: 12 weeks
measure: 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
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
References: