A Phase IV Study to Assess the Impact of the Change of Antiretroviral Treatment From Dual Therapy to Triple Therapy on Inflammation in Patients With HIV Infection

Study Overview
=================
Brief Summary
-----------------
242 patients (121 patients in each of the two treatment arms) will be included with a confirmed diagnosis of HIV-1 infection and with a stable antiretroviral treatment during more than 48 weeks with dual therapy (DTG + 3TC)

Official Title
-----------------
A Phase IV, Multicenter, Open and Randomized Study to Assess the Impact of the Change From Antiretroviral Treatment From Dual Therapy to Triple Therapy on Inflammation in Patients With Type 1 HIV Infection. InSTINCT Study

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: Dual Therapy
* Drug: Triple therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women ≥ 18 years Confirmed and documented diagnosis of HIV-1 infection Virological suppression of more than 48 weeks (confirmed with HIV RNA <50 copies / ml). The determination of the CV of a routine prior analysis of ≤ 12 weeks prior to signature of consent. ART in stable dual therapy (> 48 weeks) with DTG + 3TC Signed informed consent Negative pregnancy test in urine or blood Exclusion Criteria: Inability to obtain written informed consent to participate in the study Pregnant or breastfeeding women or those who intend to become pregnant during the study period and do not undertake to use proven contraceptive methods. Any suspicion or confirmation of resistance to TAF, 3TC, FTC, DTG or BIC. In case of have a study of baseline resistance mutations prior to the start of ART has to rule out resistance to investigational drugs. Patients with hypersensitivity to any excipient used with TAF, FTC, DTG or BIC Any chronic autoimmune or inflammatory disease Use of immunomodulatory or immunosuppressive agents, including steroids Chronic treatment with aspirin, statins and other anti-inflammatory agents Any acute infection in the last 2 months Estimated glomerular filtration rate (TFGe) <30 mg / ml / m2 measured by any of the formulas available. The determination of the TFGe of a previous routine analysis of ≤ 12 weeks prior to signing the consent is allowed Contraindication for the use of TAF Clinical condition of the patient in rapid deterioration or the investigator considers that there is no reasonable hope that the patient will finish the study Simultaneous participation in another clinical trial or research study that requires the need of treatment with other drugs outside the study or interfere with the visits of the same. Any situation that, in the opinion of the investigator, may interfere with the patient's ability to meet the treatment schedule and protocol evaluations

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Comparator: the patient will continue taking the dual therapy. Experimental: the patient Will beging to take triple therapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm:<br>they will take 1 tablet (50 mg BIC + 200 mg FTC + 25 mg TAF), orally, once a day, from the moment of randomization. | Drug: Triple therapy<br>* BIC / FTC / TAF<br>|
| Active Comparator: Comparator arm<br>they will take 1 tablet of 50 mg of DTG orally, once a day + 1 tablet of 300 mg of 3TC orally, once a day, from the randomization moment. | Drug: Dual Therapy<br>* DTG + 3TC<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sCD14 | Changes in sCD14 concentration | Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in PCR-us | Inflammation (IL-6 signaling pathways): | Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96 | 
| Changes in sCD163 | Monocyte / macrophage activation | Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96 | 
| Changes in quinurenine / tryptophan ratio | IDO-1 induction | Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96 | 
| Changes in Dimer D | Coagulation | Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96 | 
| Changes in CD4/CD8 ratio | Inmunoactivation | Screening, basal, week 23, week 24, week 47, week 48, week 95 y week 96 | 
| Changes in CD4+ |  | Throughout all the study, an average of 100 weeks | 
| Changes in viral suppression rates |  | Throughout all the study, an average of 100 weeks | 
| Longitudinal trajectories of plasma biomarkers | The differences in the trajectories of soluble inflammatory markers by comparing the slopes of each biomarker between treatment arms. Longitudinal changes in each biomarker will be compared using linear or non-linear mixed models with random intercepts, depending on the normality of the data. | Throughout all the study, an average of 100 weeks | 
| Longitudinal trajectories of CD4/CD8 ratio |  | Throughout all the study, an average of 100 weeks |