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

Study Overview
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Brief Summary
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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).

Official Title
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HIV Reservoir Dynamics After Switching to Dolutegravir in Patients With Two NRTI and a Protease Inhibitor Based Regimen. A Phase IV Open Randomized Trial

Conditions
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HIV-1

Intervention / Treatment
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* Drug: Dolutegravir
* Drug: PI
* Drug: 2 NRTI
* Drug: 2 NRTI


Participation Criteria
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Eligibility Criteria
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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: 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. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 NRTI+ Dolutegravir<br>22 patients will be treated with 2 NRTI+Dolutegravir 50 mg during 24 weeks | Drug: Dolutegravir<br> <br> Drug: 2 NRTI<br> <br> |
| Active Comparator: 2 NRTI + PI<br>22 patients will be treated with 2 NRTI + PI during 24 weeks | Drug: PI<br>* (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<br>* Other names: Fosamprenavir, atazanavir, lopinavir or darunavir;Drug: 2 NRTI<br> <br> * Other names: 2NRTI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |