There are 4 clinical trials
The aim of this study is to determine if virologically suppressed, human immunodeficiency virus type 1 (HIV-1) infected adults on an antiretroviral regimen (including 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a third agent) remain suppressed upon switching to a two-drug regimen with dolutegravir (DTG) + rilpivirine (RPV). The study will primarily assess the non-inferiority antiviral activity of switching to DTG + RPV once daily compared to continuation of current antiretroviral regimen (CAR) up to Week 48 with a switch visit for eligible subjects in the CAR group to initiate DTG + RPV therapy at Week 52. CAR will include 2 NRTIs plus 1 HIV-1 integrase inhibitor (INI), or 1 non-nucleoside reverse transcriptase inhibitor (NNRTI), or 1 protease inhibitor (PI). The study will include a 148-week open-label treatment phase, comprising of an Early Switch Phase (Day 1 to Week 52) and a Late Switch Phase (Week 52 to Week 148). The participants fulfilling the study eligibility criteria will participate in the Early Switch Phase where they will either switch from their CAR to DTG + RPV, or continue taking their CAR, until Week 52. At the end of Early Switch Phase, eligible participants will proceed to the Late Switch Phase where all participants in both DTG + RPV and CAR treatment groups will receive DTG + RPV therapy until Week 148. After Week 148, subjects may be eligible to continue to receive DTG +RPV in the Continuation Phase. The study is planned to be conducted in approximately 476 participants.
Exclusionary Laboratory Values or Clinical Assessments at Screening: - Evidence of viral resistance based on the presence of any resistance associated major PI, INI, NRTI, or NNRTI mutation and integrase (IN) resistance associated substitution R263K in any available prior resistance genotype assay results. --- R263K ---
Description: Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior antiviral activity of switching to DTG+RPV once daily compared to continuation of CAR over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced participants. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for HIV-1 RNA at Week 0 (Day 1), Week 4, 8, 12, 24, 36 and 48. Treatment with DTG + RPV were declared non-inferior to CAR if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 48 lies above -10% by Cochran-Mantel Haenszel test. The Intent-to-Treat Exposed (ITT-E) population consisted of all randomly assigned participants who received at least one dose of study drug.
Measure: Percentage of Participants With Plasma Human Immunodeficiency Virus (HIV) 1 Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 Using Snapshot Algorithm Time: Week 48.Description: Blood was collected and CD4+ cell count assessment by flow cytometery was carried out at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48 to evaluate the immunological activity of DTG + RPV once daily compared to continuation of CAR. The full set of lymphocyte sub sets was not evaluated. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Weeks 24 and 48 Time: Week 24 and 48Description: Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 24 using the FDA snapshot algorithm was assessed to evaluate the antiviral activity of DTG +RPV once daily compared to continuation of CAR. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for HIV-1 RNA at Baseline(Day 1), Week 4, 8, 12 and 24.
Measure: Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 24 Using Snapshot Algorithm Time: Week 24Description: An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE. Number of participants with common non-serious AE, SAE, drug related AE or SAE, AELD or AE with maximum grade toxicity was summarized. Common AEs were those with >5 percent incidence for either treatment. Safety Population included all randomly assigned participants who have received at least one dose of study drug.
Measure: Number of Participants With Common Non-serious Adverse Event (AE), Any Serious AE (SAE), AE of Maximum Toxicity Grade 1, 2, 3 or 4 and AE Leading to Discontinuation (AELD) Time: Up to Week 52Description: Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 to evaluate alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, blood urea nitrogen (BUN), total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Value obtained at Day 1 was considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in clinical chemistry over 48 weeks was summarized. Participants were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; grade and grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a chemistry toxicity.
Measure: Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks Time: Up to 48 weeksDescription: Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, mean corpuscular volume (MCV), red blood cell (RBC) count, white blood cell (WBC) count and platelet count. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in hematology over 48 weeks was summarized.
Measure: Number of Participants With Maximum Post-baseline Emergent Hematology Toxicities Over 48 Weeks Time: Up to 48 weeksDescription: Blood biomarker samples were collected at Baseline (Day 1) and 48 to assess hs-CRP. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess cystatin C. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in Cystatin C at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess D-Dimer. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in D-Dimer at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess FABP and soluble CD14. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Fatty Acid Binding Protein 2 (FABP) and Soluble CD14 at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess soluble CD163 and oxidized LDL. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Soluble CD163 and Oxidized Low Density Lipoprotein (LDL) at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess RBP, serum creatinine and glucose. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Retinol Binding Protein (RBP), Serum Creatinine and Glucose at Week 48 Time: Up to Week 48Description: Urine biomarker samples were collected to at Baseline (Day 1) and Week 48 to assess urine phosphate. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in Urine Phosphate at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess B2M and 25 hydroxy-vitamin D. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles). For 25 hydroxy-vitamin D, analysis of changes from Baseline was performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.
Measure: Mean Change From Baseline in Beta-2-microglobulin (B2M) (Blood and Urine), Urine RBP and 25 Hydroxy-vitamin D at Week 48 Time: Up to Week 48Description: Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine albumin/creatinine ratio and urine protein/creatinine ratio. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type 1 Collagen C-telopeptides and sVCAM. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles). For bone-specific alkaline phosphatase, procollagen 1-N-propeptide, osteocalcin and type 1 collagen C-telopeptide, analyses of changes from Baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.
Measure: Mean Change From Baseline in Bone-specific Alkaline Phosphatase, Procollagen 1 N-terminal Propeptide, Osteocalcin, Type 1 Collagen C-telopeptides and Soluble Vascular Cell Adhesion Molecule (sVCAM) at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess IL-6. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in Interleukin 6 (IL-6) at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess insulin resistance. Change from Baseline was calculated as value at indicated time point minus Baseline value. The homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR ) index , the product of basal glucose and insulin levels divided by 22.5, is regarded as a simple , inexpensive , and reliable surrogate measure of insulin resistance.
Measure: Mean Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Week 48 Time: Up to Week 48Description: Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Fasting Lipids at Weeks 24 and 48 Time: Up to Week 48Description: Genotypic resistance data for drugs received for participants meeting confirmed virologic withdrawal criteria are presented below. Confirmed Virologic Withdrawal (CVW) Population consisted of all participants in the ITT-E Population who met CVW (1 CVW per arm). NA indicates Not applicable based on drugs were not received. Genotypic Resistance Data only shown for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria.
Measure: Genotypic Resistance Data for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria Time: Week 48Description: Phenotypic resistance data for drugs received for participants meeting confirmed virologic withdrawal criteria are presented below. Confirmed Virologic Withdrawal (CVW) Population consisted of all participants in the ITT-E Population who met CVW (1 CVW per arm). NA indicates Not applicable based on drugs were not received. Phenotypic Resistance Data only shown for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria.
Measure: Phenotypic Resistance Data for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria Time: Week 48Description: Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 4, 24 and 48. Pre-dose concentrations of DTG and RPV at Weeks 4, 24 and 48 or withdrawal were summarized for the participants switching to DTG + RPV in the early switch phase. Pharmacokinetic (PK) Parameter Population consisted of all participants who received DTG +RPV and provided at least one evaluable estimate of predose concentration (C0). Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Pre-dose Concentrations of DTG and RPV at Weeks 4, 24 and 48 or Withdrawal in Participants Switching to DTG + RPV Time: Pre-dose at Week 4, 24 and 48 or at withdrawal visitDescription: Two blood samples were collected pre-dose for DTG and RPV at Weeks 2 and 8 only for the first 20 participants who switch from EFV or NVP to DTG+RPV, in addition to the pre-dose blood sample collected at Week 4 for all subjects. One blood sample was collected pre-dose for EFV or NVP at Week 2 for the first 20 participants who switch from EFV or NVP to DTG + RPV. PK Parameter NNRTI Subset Extra Sampling Population consisted of the first approximately 20 participants in the PK Parameter NNRTI Subset population who have extra PK samples at weeks 2 and 8. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Pre-dose Concentrations of DTG and RPV at Weeks 2, 4 and 8 in the First 20 Participants Who Switch From Efavirenz (EFV) or Nevirapine (NVP) to DTG + RPV Time: Pre-dose at Week 2, 4 and 8Description: Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the FDA snapshot algorithm was assessed by Baseline third agent class to assess the impact of Baseline third agent class (INSTI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. Plasma samples were collected for HIV-1 RNA at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48. The analysis was done using cochran-mantel haenszel test stratified by current antiretroviral third-agent class. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm by Baseline Third Agent Treatment Class Time: Up to Week 48Description: Blood for CD4 cell count assessment by flow cytometery was carried out at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48 to assess the impact of Baseline third agent class (INSTI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. The full set of lymphocyte sub sets was not evaluated. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Week 48 by Baseline Third Agent Treatment Class Time: Baseline and up to Week 48Description: An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any AE, AELD or AE with maximum grade toxicity experienced by any one participant over 48 weeks by Baseline third agent class (INSTI, NNRTI, or PI) was summarized. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Number of Participants With Any AE, AELD or AE With Grade 1, 2, 3 or 4 Toxicity Over 48 Weeks by Baseline Third Agent Treatment Class Time: Up to 48 weeksDescription: Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 to evaluate ALT, albumin, ALP, AST, total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, BUN, total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum toxicity grade post-baseline in chemistry parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) was summarized.
Measure: Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class Time: Up to 48 weeksDescription: Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCV, RBC count, WBC count and platelet count. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum toxicity grade post-baseline in hematology parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) was summarized.
Measure: Number of Participants With Maximum Post-baseline Emergent Hematology Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class Time: Up to 48 weeksDescription: For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain genotype data on as many samples as possible. Samples for drug resistance testing (genotypic) were to be collected at Day 1. Number of participants with genotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome has not been analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.
Measure: Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class Time: Week 48Description: For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain phenotype data on as many samples as possible. Samples for drug resistance testing (phenotypic) were to be collected at Day 1. Number of participants with phenotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome was not analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.
Measure: Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class Time: Week 48Description: Blood samples were collected at Baseline (Day 1), 24 and 48 to assess fasting lipids which included total cholesterol (CHO), LDL cholesterol, HDL cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Change From Baseline in Fasting Lipids at Weeks 24 and 48 by Baseline Third Agent Treatment Class Time: Baseline and up to Week 48Description: The Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Between and within treatment group comparisons were assessed on change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 4, 24 and 48 or withdrawal from the study. Change from Baseline in Symptom count and symptom bother score have been summarized. The symptom bother score is based on the score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). The symptom bother score ranges from 0 to 80. Last observation carried forward (LOCF) was used as primary method of analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 4, 24 and 48 or Withdrawal From the Study Time: Up to Week 48Description: The HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0-6 where a higher score indicates the greater improvement in the past few weeks. These items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscales: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). The HIV TSQ was administered as a paper questionnaire. Between and within treatment group comparisons were assessed on change from Baseline treatment satisfaction using the HIV TSQ at Weeks 4, 24 and 48 or withdrawal from the study. Total score, lifestyle/ease score and General satisfaction/clinical sub-score (CS) have been summarized. LOCF was used as primary method of analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Change From Baseline Treatment Satisfaction Using the HIV Treatment Satisfaction Questionnaire (HIV TSQ) at Weeks 4, 24 and 48 or Withdrawal From the Study Time: Up to Week 48The aim of this study is to determine if virologically suppressed human immunodeficiency virus type 1 (HIV-1) infected adults on an antiretroviral regimen (including 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a third agent) remain suppressed upon switching to a two-drug regimen with dolutegravir (DTG) + rilpivirine (RPV). The study will primarily assess the non-inferiority antiviral activity of switching to DTG + RPV once daily compared to continuation of current antiretroviral regimen (CAR) up to Week 48 with a switch visit for eligible subjects in the CAR group to initiate DTG + RPV therapy at Week 52. CAR will include 2 NRTIs plus 1 HIV-1 integrase inhibitor (INI), or 1 non-nucleoside reverse transcriptase inhibitor (NNRTI), or 1 protease inhibitor (PI). The study will include a 148-week open-label treatment phase, comprising of an Early Switch Phase (Day 1 to Week 52) and a Late Switch Phase (Week 52 to Week 148). The participants fulfilling the study eligibility criteria will participate in the Early Switch Phase where they will either switch from their CAR to DTG + RPV, or continue taking their CAR, until Week 52. At the end of Early Switch Phase, eligible participants will proceed to the Late Switch Phase where all participants in both DTG + RPV and CAR treatment groups will receive DTG + RPV therapy until Week 148. After Week 148, subjects may be eligible to continue to receive DTG +RPV in the Continuation Phase. The study is planned to be conducted in approximately 476 participants.
Exclusionary Laboratory Values or Clinical Assessments at Screening: - Evidence of viral resistance based on the presence of any resistance associated major PI, INI, NRTI, or NNRTI mutation and integrase (IN) resistance associated substitution R263K in any available prior resistance genotype assay results. --- R263K ---
Description: Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior antiviral activity of switching to DTG + RPV once daily compared to continuation of CAR over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced participants. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for HIV-1 RNA at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48. Treatment with DTG + RPV was declared non-inferior to CAR if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 48 lies above -10% by Cochran-Mantel Haenszel test. The Intent-to-Treat Exposed (ITT-E) population consisted of all randomly assigned participants who received at least one dose of study drug.
Measure: Percentage of Participants With Plasma Human Immunodeficiency Virus (HIV) 1 Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48 Using Snapshot Algorithm Time: Week 48Description: Blood was collected and CD4+ cell count assessment by flow cytometery was carried out at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48 to evaluate the immunological activity of DTG + RPV once daily compared to continuation of CAR. The full set of lymphocyte sub sets was not evaluated. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Weeks 24 and 48 Time: Week 24 and 48Description: Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 24 using the FDA snapshot algorithm was assessed to evaluate the antiviral activity of DTG + RPV once daily compared to continuation of CAR. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for HIV-1 RNA at Baseline (Day 1), Week 4, 8, 12 and 24.
Measure: Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 24 Using Snapshot Algorithm Time: Week 24Description: An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE. Number of participants with common non-serious AE, SAE, AELD or AE with maximum grade toxicity experienced over Week 48 was summarized. Common AEs were those with >5 percent incidence for either treatment. Safety Population included all randomly assigned participants who have received at least one dose of study drug.
Measure: Number of Participants With Common Non-serious Adverse Event (AE), Any Serious AE (SAE), AE of Maximum Toxicity Grade 1, 2, 3 or 4, AE Leading to Discontinuation (AELD) Time: Up to 52 weeksDescription: Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 to evaluate alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, blood urea nitrogen (BUN), total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Value obtained at Day 1 was considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in clinical chemistry over 48 weeks was summarized. Participants were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening.
Measure: Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks Time: Up to 48 weeksDescription: Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, mean corpuscular volume (MCV), red blood cell (RBC) count, white blood cell (WBC) count and platelet count. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in hematology over 48 weeks was summarized. Participants were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening
Measure: Number of Participants With Maximum Post-baseline Emergent Hematology Toxicities Over 48 Weeks Time: Up to 48 weeksDescription: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess hs-CRP. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess cystatin C Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in Cystatin C at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess D-Dimer. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in D-Dimer at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess FABP and soluble CD14. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Fatty Acid Binding Protein 2 (FABP) and Soluble CD14 at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess soluble CD163 and oxidized LDL. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Soluble CD163 and Oxidized Low Density Lipoprotein (LDL) at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess RBP, serum creatinine and glucose. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Retinol Binding Protein (RBP), Serum Creatinine and Glucose at Week 48 Time: Up to Week 48Description: Urine biomarker samples were collected to at Baseline (Day 1) and Week 48 to assess urine phosphate. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in Urine Phosphate at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess B2M and 25 hydroxy-vitamin D. Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine B2M and urine RBP. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles). For 25 hydroxy-vitamin D, analysis of changes from baseline was performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.
Measure: Mean Change From Baseline in Beta-2-microglobulin (B2M) (Blood and Urine), Urine RBP and 25 Hydroxy-vitamin D at Week 48 Time: Up to Week 48Description: Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine albumin/creatinine ratio and urine protein/creatinine ratio. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type I Collagen C-Telopeptides and sVCAM. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles). For bone-specific alkaline phosphatase, procollagen 1-N-propeptide, osteocalcin and type 1 collagen C-telopeptide, analyses of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.
Measure: Mean Change From Baseline in Bone-specific Alkaline Phosphatase, Procollagen 1 N-terminal Propeptide, Osteocalcin, Type I Collagen C-Telopeptides and Soluble Vascular Cell Adhesion Molecule (sVCAM) at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess IL-6. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Measure: Mean Change From Baseline in Interleukin 6 (IL-6) at Week 48 Time: Up to Week 48Description: Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess insulin resistance. Change from Baseline was calculated as value at indicated time point minus Baseline value. The homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) index, the product of basal glucose and insulin levels divided by 22.5 (1,2), is regarded as a simple, inexpensive, and reliable surrogate measure of insulin resistance.
Measure: Mean Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Week 48 Time: Up to Week 48Description: Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Mean Change From Baseline in Fasting Lipids at Weeks 24 and 48 Time: Up to Week 48Description: Genotypic resistance data for drugs received for participants meeting confirmed virologic withdrawal criteria are presented below. Confirmed Virologic Withdrawal (CVW) Population consisted of all participants in the ITT-E Population who met CVW (1 CVW per arm). NA indicate that data were not applicable based on drugs not received. Genotypic Resistance Data only shown for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria.
Measure: Genotypic Resistance Data for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria Time: Day 1Description: Phenotypic resistance data for drugs received for participants meeting confirmed virologic withdrawal criteria are presented below. Confirmed Virologic Withdrawal (CVW) Population consisted of all participants in the ITT-E Population who met CVW (1 CVW per arm). NA indicate that data were not applicable based on drugs were not received. Phenotypic Resistance Data only shown for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria.
Measure: Phenotypic Resistance Data for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria Time: Day 1Description: Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 4, 24 and 48. Pre-dose concentrations of DTG and RPV at Weeks 4, 24 and 48 or withdrawal were summarized for the participants switching to DTG + RPV in the early switch phase. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles). Pharmacokinetic (PK) Parameter Population consisted of all participants who received DTG +RPV and provided at least one evaluable estimate of predose concentration (C0).
Measure: Pre-dose Concentrations of DTG and RPV at Weeks 4, 24 and 48 or Withdrawal in Participants Switching to DTG + RPV Time: Pre-dose at Week 4, 24 and 48 or at withdrawal visitDescription: Two blood samples were collected pre-dose for DTG and RPV at Weeks 2 and 8 only for the first 20 participants who switch from EFV or NVP to DTG + RPV. One blood sample was collected pre-dose for EFV or NVP at Week 2 for the first 20 participants who switch from EFV or NVP to DTG + RPV. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Pre-dose Concentrations of DTG and RPV at Weeks 2, 4 and 8 in the First 20 Participants Who Switch From Efavirenz (EFV) or Nevirapine (NVP) to DTG + RPV Time: Pre-dose at Week 2, 4 and 8Description: Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the FDA snapshot algorithm was assessed by Baseline third agent class to assess the impact of Baseline third agent class (INI, NNRTI, or PI) on efficacy of DTG +RPV compared to continuation of CAR. Plasma samples were collected for HIV-1 RNA at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48. The analysis was done using cochran-mantel haenszel test stratified by current antiretroviral third-agent class and age group. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm by Baseline Third Agent Treatment Class Time: Up to Week 48Description: Blood for CD4 cell count assessment by flow cytometery was carried out at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48 to assess the impact of Baseline third agent class (INI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. The full set of lymphocyte sub sets was not evaluated. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Week 48 by Baseline Third Agent Treatment Class Time: Baseline and up to Week 48Description: An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any AE, AELD or AE with maximum grade toxicity experienced by any one participant over 48 weeks by Baseline third agent class (INI, NNRTI, or PI) was summarized. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Number of Participants With Any AE, AELD or AE With Grade 1, 2, 3 or 4 Toxicity Over 48 Weeks by Baseline Third Agent Treatment Class Time: Up to 48 weeksDescription: Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 to evaluate ALT, albumin, ALP, AST, total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, BUN, total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum toxicity grade post-baseline in chemistry parameters over 48 weeks by Baseline third agent treatment class (INI, NNRTI, PI) was summarized. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class Time: Up to 48 weeksDescription: Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCV, RBC count, WBC count and platelet count. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum toxicity grade post-baseline in hematology parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) was summarized. Participants were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening
Measure: Number of Participants With Maximum Post-baseline Emergent Hematology Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class Time: Up to 48 weeksDescription: For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain genotype data on as many samples as possible. Samples for drug resistance testing (genotypic) were to be collected at Day 1. Number of participants with genotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome has not been analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.
Measure: Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class Time: Day 1Description: For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain phenotype data on as many samples as possible. Samples for drug resistance testing (phenotypic) were to be collected at Day 1. Number of participants with phenotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome was not analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.
Measure: Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class Time: Day 1Description: Blood samples were collected at Baseline (Day 1), 24 and 48 to assess fasting lipids which included total cholesterol (CHO), LDL cholesterol, HDL cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Change From Baseline in Fasting Lipids at Weeks 24 and 48 by Baseline Third Agent Treatment Class Time: Up to Week 48Description: The Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Between and within treatment group comparisons were assessed on change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 4, 24 and 48 or withdrawal from the study. Change from Baseline in Symptom count and symptom bother score have been summarized. The symptom bother score is based on the score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). The symptom bother score ranges from 0 to 80. Last observation carried forward (LOCF) was used as primary method of analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 4, 24 and 48 or Withdrawal From the Study Time: Up to Week 48Description: The HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0-6 where a higher score indicates the greater improvement in the past few weeks. These items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscales: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). The HIV TSQ was administered as a paper questionnaire. Between and within treatment group comparisons were assessed on change from Baseline treatment satisfaction using the HIV TSQ at Weeks 4, 24 and 48 or withdrawal from the study. Total score, lifestyle/ease score and General satisfaction/clinical sub-score (CS) have been summarized. LOCF was used as primary method of analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measure: Change From Baseline Treatment Satisfaction Using the HIV Treatment Satisfaction Questionnaire (HIV TSQ) at Weeks 4, 24 and 48 or Withdrawal From the Study Time: Up to Week 48The availability of antiretroviral therapy has led to a reduction in morbidity and mortality in patients with chronic HIV infection. The treatment, however, is not free of side effects, has potential interactions with other medications, is expensive and can be complex, especially in those patients who are very experienced and with mutations that give them resistance to multiple drugs. For this reason, the development of simplification strategies that avoid unnecessary exposure to antiretroviral agents remains of great interest. This is a simplification study, in which the investigators try to evaluate that with less medication the investigator can maintain the same virological control of the disease. This would mean a lower burden of medication for patients, facilitating its administration and reducing the number of unwanted side effects. Specifically, the investigators intend to evaluate the treatment with Darunavir / cobicistat plus Dolutegravir as a simplification strategy, since both drugs are taken once a day, have a powerful antiviral activity, even against antiretroviral resistant viruses, and are among the best tolerated (with fewer side effects). The results reported in some observational studies suggest that two-drug therapy (bitherapy) as a simplification strategy could also be safe and effective, however, as far as the investigators know, there are no data and clinical trials that specifically evaluate darunavir / cobicistat plus dolutegravir as a strategy of simplification.
T66I, 74M, E92Q, T97A, F121Y, E138A/K, G140A/S, Y143R/H/C, S147G, Q148H/K/R, N155H AND R263K) in historical genotyping tests. --- T66I --- --- E92Q --- --- T97A --- --- F121Y --- --- E138A --- --- G140A --- --- Y143R --- --- S147G --- --- Q148H --- --- N155H --- --- R263K ---
Description: HIV-1 RNA < 50 copies/mL using a Time to Loss of Virological Response (TLOVR).
Measure: Plasma HIV-1 RNA < 50 copies/mL at 48 weeks Time: week 48Description: Percentage of patients developing ART-associated adverse events leading to treatment discontinuation.
Measure: Percentage of patients developing ART-associated adverse events Time: Since baseline to week 48Description: CD4+ cell count changes
Measure: Changes in CD4+ cell count Time: Since baseline to week 48Description: Emergence of new mutations in HIV-1 protease and integrase assessed with a genotyping test (attempted on any post Day 1 sample with HIV-1 RNA ≥ 50 copies/mL).
Measure: Emergence of new mutations in HIV-1 protease and integrase Time: Baseline and in case of virological failure, defined as ≥ 50 copies/mL in 2 consecutive determinations or a single HIV-1 RNA values > 1000 copies/mL. We can observe a virological failure throughout the study (from baseline to week 48)Description: HIV-1 RNA< 50 copies/mL at 24 weeks by TLOVR
Measure: Plasma HIV-1 RNA < 50 copies/mL at 24 weeks Time: Week 24Description: HIV-1 RNA < 50 copies/mL at 24 and 48 weeks using the FDA snapshot analysis (sensitivity analysis).
Measure: Plasma HIV-1 RNA < 50 copies/mL at 24 and 48 weeks Time: Week 24 and 48Description: Description of plasmatic trough levels of DTG and DRV/cobi in the experimental group, and in those patients experiencing virological failure.
Measure: DTG and DRV/cobi plasma concentration Time: Week 4Description: ART prices
Measure: Cost associated with the antirretroviral treatment of the study Time: Since baseline to week 48Description: Prices of clinical controls during the study
Measure: Estimated costs of clinical controls Time: Since baseline to week 48The primary objective of the study is to evaluate the capacity of Dolutegravir + Rilpivirine vs. continued triple combination HAART to maintain plasma HIV RNA ≤ 50 copies/ml throughout 24 weeks in patients with plasma HIV RNA ≤ 50 copies/mL for at least 2 years under conventional HAART (2 NNRTI + 3rd agent). The main secondary objectives are the following: - % of virologic success (plasma viral load ≤ 50 copies/mL) at W24 and W48 - % of patients who maintain a plasma viral load ≤ 50 copies / ml from D0 to W48 - % of virological failure defined by two consecutive plasma viral load > 50 copies/mL - Profile of genotypic resistance in case of virological failure. The trial will be conducted according to the design below, in 3 steps: - Step 1: enrollment of 80 patients (40 in each arm) - Step 2: enrollment on hold until W16 data from the 40 patients enrolled in the intervention arm have been analyzed. - Step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/mL from D0 to W16 is significantly > 70%, which translates in a maximum of 6 virologic failures.
- No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S - Negative HBs Ag - Informed consent form signed by patient and investigator - A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study - Patient covered with health insurance - Effective contraception Exclusion Criteria: - HIV-2 infection - Dialysis or severe renal failure (creatinine clearance < 30 ml/min) - History of decompensated liver disease - History of HIV-associated neurocognitive disorders - AST or ALT > 5 x ULN - Positive HBc Ac and negative HBs Ac - Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug - Current pregnancy or breastfeeding - Patient involved in another research that precludes enrolment in another trial - Patient under guardianship, or deprived of liberty by a court or administrative decision. --- T66K --- --- G118R --- --- V151L --- --- S153F --- --- R263K ---
Description: Evolution of the HIV-DNA between Day 0 and week 48
Measure: Measure of the HIV-DNA between day 0 and week 48 Time: W48Description: Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0
Measure: Measure of CD4 lymphocytes at week 24 compared to day 0 Time: Week 24Description: Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0
Measure: Measure of CD4 lymphocytes at Week 48 compared to Day 0 Time: Week 48Description: Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events
Measure: Number of patients with adverse events of grade 2 to 4 Time: Week 48Description: Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0
Measure: Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0 Time: Week 24Description: Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0
Measure: Measure of changes in serum lipid parameters at week 48 to Day 0 Time: Week 48Description: Changes in fat mass distribution at Week 24 compared to Day 0
Measure: Measure of changes in fat mass distribution at week 24 compared to Day 0 Time: Week 24Description: Changes in fat mass distribution at Week 48 compared to Day 0
Measure: Measure of changes in fat mass distribution at Week 48 compared to Day 0 Time: Week 48Description: Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire
Measure: Measure of adherence to treatment at Week 24 compared to Day 0 Time: Week 24Description: Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire
Measure: Measure of adherence to treatment at Week 48 compared to Day 0 Time: Week 48Description: Assessment of patient satisfaction for their treatment at D0 by questionnaire
Measure: Measure of patient satisfaction for their treatment at Day 0 Time: Day 0Description: Assessment of patient satisfaction for their treatment at Week 24 by questionnaire
Measure: Measure of patient satisfaction for their treatment at Week 24 Time: Week 24Description: Assessment of patient satisfaction for their treatment at Week 48 by questionnaire
Measure: Measure of patient satisfaction for their treatment at Week 48 Time: Week 48Description: Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .
Measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 . Time: Week 24Description: Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .
Measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 . Time: Week 48Description: Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4
Measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4 Time: Week 4Description: Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24
Measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24 Time: Week 24