HIV-1 Infection
Conditions
Keywords
Raltegravir, Etravirine, aged, 45 and over, Viral load, Efficacy, Safety
Brief summary
This multicenter, international, non randomized (single arm), open, phase II trial aims to evaluate the capacity of the dual combination raltegravir/etravirine to maintain virological success in virologically suppressed HIV-1 infected patients, of at least 45 years of age, switching from a boosted PI-containing regimen. Patients will be followed for 96 weeks. The primary endpoint was the proportion of participants with virological success at 48 weeks. Virological success is defined as the absence of 2 consecutive plasma viral load \>50 copies/mL within 2 to 4 weeks apart. The study was designed to show an efficacy \>90%, assuming a success rate \>95%, with a power of 80% and a 5%type-1 error. A total of 160 individuals was required to achieve the objective. The principal secondary endpoint is the proportion of patients in therapeutic success up to week 48 and 96.
Interventions
DRUGraltegravir and etravirine
Raltegravir (RAL, ISENTRESS®) 400 mg tablets will be administered as one 400 mg oral tablet PO twice daily (800 mg per day) after a meal. Etravirine (ETR, INTELENCE®) 200 mg tablets will be administered as one 200 mg oral tablet PO twice daily (400 mg per day) after a meal.
Sponsors
ANRS, Emerging Infectious Diseases
Merck Sharp & Dohme LLC
Janssen-Cilag Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented HIV-1 infection * Age ≥ 45 years * Naïve to integrase inhibitor and etravirine * At least 6 months of stable antiretroviral therapy (ART) including a boosted protease inhibitor, whatever the number of combined drugs * HIV-RNA plasma VL ≤ 50 copies/mL during the last 24 months prior to screening visit (Week-6/Week-4), documented by at least 4 time-points with no more than one blip in HIV-RNA plasma viral load between 51 and 200 copies/mL * HIV-RNA plasma VL ≤ 50 copies/mL at screening visit (Week-6/Week-4) * A genotype is available (on amplified DNA at Week-6/Week-4 Visit and/or on RNA in the medical history of the patient) and shows a virus sensitive to ETR OR no genotype is available (amplification failure on DNA at Week-6/Week-4 Visit and no genotype in the medical history of the patient), there are no virological failure on NNRTI in the medical history * CD4+ lymphocytes \> 200 cells/mm3 * Creatinine \< 2.5 x ULN * CPK (Creatine Phospho Kinase) \< 6 ULN (Upper Limit of Normal) * AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase) \< 5 ULN * Hemoglobin \> 10 g/dL * Platelets \> 100 000/mm3 * Negative urinary pregnancy test and use of efficient contraception for women of childbearing potential * For French participants only: subject enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme), article L1121-11 of the Public health code * Patients with a coverage from a social health * Signed informed consent
Exclusion criteria
* Previous exposure to raltegravir or etravirine * Presence of any documented integrase inhibitor mutation on DNA genotype at Week-6/Week-4 and/or on RNA in the medical history of the patient * Positive hepatitis B HBsAg or Positive HBc Ac and negative HBs Ac * HIV-2 infection * Active viral hepatitis C requiring a specific treatment during the 24 months of the trial * Patient with a history of non-compliance or irregular follow-up * Initiation of a concomitant anti-hypercholesterolemia (e.g. statins) or antidiabetic treatment within the last 3 months prior the screening visit (Week-6 /Week-4) * Patient using: Clopidogrel (Plavix®), Prasugrel (Effient®), Ticagrelor (Brilinta®), Ticlopidine (Ticlid®), Flurbiprofen (Antadys® - Cebutid®), Rifampin (Rifampicin® - Rifadin® - RofactMC - Rifater®), Rifapentine (Priftin®), St John's wort, Carbamazepine (Tegretol®), Phenobarbital, Phenytoin (Dilantin®),Avanafil (Stendra™), Triazolam (Halcion®) * Concomitant treatment using interferon, interleukins or any other immunotherapy or chemotherapy * Concomitant prophylactic or curative treatment for an opportunistic infection * All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with trial protocol compliance, adherence and/or trial treatment tolerance * Subjects under judicial protection due to temporarily and slightly diminished mental or physical faculties, or under legal guardianship * Subjects participating in another clinical trial evaluating different therapies and including an exclusion period that is still in force during the screening phase * Pregnant women or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96 | at week48 and at week 96 | Virological success is defined as the absence of 2 consecutive plasma viral loads (VL) \> 50 copies/mL within 2 to 4 weeks of a dual raltegravir/etravirine regimen. The proportion of patients who maintained viral suppression under raltegravir plus etravirine was 99.4% (95% confidence interval (95% CI:95.6 -99.9) at week 48 and 98.7% (95% CI: 95.0 -99.7) at week 96 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Therapeutic Success at Week 48 and Week 96 | weeks 48 and 96 | Therapeutic success was defined as the absence of virological failure (i.e. 2 consecutive plasma viral loads (VL) \> 50 copies/mL within 2 to 4 weeks) and the absence of treatment interruption due to adverse event judged by DSMB as related to the study treatment or procedure |
| Percentage of Patients With Trial Treatment Interruption at Week 48 and Week 96 | weeks 48 and 96 | — |
| Percentage of Patients With With Grade Virological Failure (HIV-RNA Plasma VL Between 51 and 200 Copies/mL) | weeks 48 and 96 | — |
| Median Time of Virological Failure | week 96 | Time between the date of the study treatment initiation and the date of virological failure |
| Percentage of Patients With High Grade of Virological Failure Defined as HIV RNA > 200 Copies/mL | weeks 48 and 96 | — |
| Number of Patients With RAL and/or ETR Resistance Mutations Among Those With Virological Failure | week 96 | — |
| Factors Associated With the Occurrence of Plasma HIV-RNA Viral Load > 50 Copies/mL | week 96 | — |
| Evolution of Total Cell-associated HIV-DNA | from day 0 to week 48 and week 96 | — |
| Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio | from day 0 to week 48 and week 96 | — |
| Number of Participants Experiencing Adverse Events and Effects | From day 0 to week 48 and week 96 | Number of all clinical and biological adverse events effects. Number of grade 3 or 4 clinical and biological adverse events and effects. |
| Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia) | from day 0 to week 96 | — |
| Evolution of the Calibrated 5-year Framingham Risk Score | from day 0 to week 48 and at week 96 | The Framingham risk score is expressed as a percentage. Higher scores mean a worse outcome and lower scores mean better outcome. Median percent change expressed as median (interquartile range (IQR)) |
| Percent Change of Renal Function | from day 0 to week 96 | Percent change of the estimated Glomerular Filtration Rate (eGFR) calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Calculator) formula |
| Evolution of Body Fat Distribution From Day 0 to W96 (DXA Scan Sub-study, 80 Patients) | from day 0 to week 96 | Evolution of total fat mass, limb fat and trunk fat from day 0 to week 96 |
| Sub-study: Bone Mineral Density | from day 0, to week 48 and week 96 | • Evolution of bone mineral density (BMD) measured by DXA scans (DXA scan sub-study, 81 patients) * Lumbar spine BMD, mg/cm2 * Total hip BMD, mg/cm2 |
| Percentage of Participants With Detectable Seminal HIV-RNA Viral Load at Week 48 | week 48 | • Assessment of HIV-RNA viral load in human male genital compartment (20 patients) at week 48 |
| Inflammatory Parameters | from day 0 to week 96 | • Evolution of the inflammation markers (IL-6hs, sCD14, sCD163, D-Dimers, IP-10, IgG, CRPus and insulin) on frozen plasma aliquots |
| Percentage of Participants Reporting a Very Good or an Excellent Quality of Life at Day 0, Weeks 48 and 96 | day 0 and weeks 48 and 96 | — |
| Percentage of Participants Compliant With Treatment Program. | at week 0, week 48, and week 96 | The compliance rate was estimated as the number of pills consumed (recorded using the self-reported 90 questionnaire) divided by the number of pills theoretically consumed, classified as low (80%), medium (80%-95%) or high (95%). |
| Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots | from day 0, to week 48 | We measured the Anti-mullerian Hormone (AMH) level to evaluate the ovarian reserve (from D0 to W48) |
| Evolution of the Level of MCP1 From D0 to W48 on Frozen Samples | from day 0, to week 48 | — |
| Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | from day 0, to week 96 | Metabolic markers measures are total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides. Inflammatory and innate immune activation markers measures are: IL-6hs, sCD14, sCD163, D-Dimers, IP-10, IgG, hsCRP and Insulin. Ovarian reserve measure is AMH |
| Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | from day 0, to week 96 | BMI, Hip circumference, Waist circumference, waist/hip ratio, Limb fat, Trunk fat, Total fat, Limb lean, Trunk lean, and Total lean |
Countries
France, Spain
Contacts
PRINCIPAL_INVESTIGATORChristine Katlama, MD
Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
STUDY_CHAIRJacques Reynes, MD
Département des Maladies Infectieuses et Tropicales Hôpital Gui de Chauliac, CHU de Montpellier France
STUDY_DIRECTORDominique Costagliola, PhD
Inserm UMR S 1136 Université Pierre et Marie Curie Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Paris, France
Participant flow
Recruitment details
Between January and November 2015, 219 patients from 20 sites were screened and 170 patients were enrolled in the study.
Pre-assignment details
Five patients did not initiate the trial treatment by their own decision, leaving 165 patients for the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir and Etravirine raltegravir and etravirine: Raltegravir (RAL, ISENTRESS®) 400 mg tablets will be administered as one 400 mg oral tablet PO twice daily (800 mg per day) after a meal.
Etravirine (ETR, INTELENCE®) 200 mg tablets will be administered as one 200 mg oral tablet PO twice daily (400 mg per day) after a meal. | 165 |
| Total | 165 |
Baseline characteristics
| Characteristic | Raltegravir and Etravirine |
|---|---|
| Active smoking | 60 Participants |
| Age, Continuous | 52 years |
| Alcohol use (>2 glasses/day) | 14 Participants |
| Antiretroviral treatment (ART) duration | 16.9 years |
| Antiretroviral treatment daily dosing once daily | 120 Participants |
| Antiretroviral treatment daily dosing twice daily | 45 Participants |
| Body Mass Index (BMI) | 24.3 kg/m^2 |
| cART at screening 2NRTIs + PI/r | 107 Participants |
| cART at screening NNRTI + PI/r | 11 Participants |
| cART at screening Others | 12 Participants |
| cART at screening PI/r | 35 Participants |
| CD4/CD8 ratio at screening | 0.94 ratio |
| CD4 cell count at screening | 700 cells/mm^3 |
| CD4 nadir cell count | 209 cells/mm^3 |
| CD8 cell count at screening | 678 cells/mm^3 |
| CDC stage C | 36 Participants |
| Comorbidities Cardiovascular | 8 Participants |
| Comorbidities Diabetes | 10 Participants |
| Comorbidities Dyslipidemia | 53 Participants |
| Comorbidities High blood pressure | 45 Participants |
| Duration of last combined antiretroviral therapy (cART) | 58 Months |
| Duration of suppressed HIV viremia (<50 copies/ml), | 6.9 years |
| Estimated glomerular filtration rate (eGFR, CKD-EPI method) | 93.9 mL/min/1.73 m^2 |
| Former smokers | 31 Participants |
| Glycaemia | 5.2 mmol/L |
| HDL cholesterol | 1.3 mmol/L |
| Hepatitis C co-infection | 16 Participants |
| Hip circumference | 95 cm |
| LDL cholesterol | 3.2 mmol/L |
| Non-HDL cholesterol | 3.9 mmol/L |
| Race/Ethnicity, Customized Caucasian | 124 Participants |
| Race/Ethnicity, Customized Others | 17 Participants |
| Race/Ethnicity, Customized Sub-saharan Africa | 24 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 117 Participants |
| Time since HIV diagnosis | 19.8 years |
| Total cholesterol | 5.4 mmol/L |
| Transmission group Heterosexual | 72 Participants |
| Transmission group Men who have Sex with Men | 66 Participants |
| Transmission group Others/Unknown | 27 Participants |
| Triglycerides | 1.3 mmol/L |
| Triglycerides/HDL ratio | 1.0 ratio |
| Viruses with mutations that could potentially impact etravirine | 18 Participants |
| Waist circumference | 92 cm |
| Waist/Hip ratio | 0.97 ratio |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 165 |
| other Total, other adverse events | 23 / 165 |
| serious Total, serious adverse events | 26 / 165 |
Outcome results
Primary
Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96
Virological success is defined as the absence of 2 consecutive plasma viral loads (VL) \> 50 copies/mL within 2 to 4 weeks of a dual raltegravir/etravirine regimen. The proportion of patients who maintained viral suppression under raltegravir plus etravirine was 99.4% (95% confidence interval (95% CI:95.6 -99.9) at week 48 and 98.7% (95% CI: 95.0 -99.7) at week 96
Time frame: at week48 and at week 96
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir and Etravirine | Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96 | at week 48 | 99.4 percentage of participant |
| Raltegravir and Etravirine | Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96 | at week 96 | 98.7 percentage of participant |
Secondary
Evolution of Body Fat Distribution From Day 0 to W96 (DXA Scan Sub-study, 80 Patients)
Evolution of total fat mass, limb fat and trunk fat from day 0 to week 96
Time frame: from day 0 to week 96
Population: Five participants were not evaluated at week 96
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Evolution of Body Fat Distribution From Day 0 to W96 (DXA Scan Sub-study, 80 Patients) | Total fat mass, Kg | 12.2 percentage of change |
| Raltegravir and Etravirine | Evolution of Body Fat Distribution From Day 0 to W96 (DXA Scan Sub-study, 80 Patients) | Limb fat, Kg | 11.6 percentage of change |
| Raltegravir and Etravirine | Evolution of Body Fat Distribution From Day 0 to W96 (DXA Scan Sub-study, 80 Patients) | Trunk fat, Kg | 12.2 percentage of change |
Secondary
Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio
Time frame: from day 0 to week 48 and week 96
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio | CD4: 0-48 week | 1.1 percentage of change |
| Raltegravir and Etravirine | Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio | CD8: 0-48 week | -1.8 percentage of change |
| Raltegravir and Etravirine | Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio | CD4/CD8: 0-48 week | 5.7 percentage of change |
| Raltegravir and Etravirine | Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio | CD4: 0-96 week | 5.0 percentage of change |
| Raltegravir and Etravirine | Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio | CD8: 0-96 week | -5.2 percentage of change |
| Raltegravir and Etravirine | Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio | CD4/CD8: 0-96 week | 7.4 percentage of change |
Secondary
Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia)
Time frame: from day 0 to week 96
Population: the number analyzed in one or more rows differs from overall number analyzed due to the Non determined data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia) | fasting triglycerides | -18.8 percentage of change |
| Raltegravir and Etravirine | Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia) | total cholesterol | -0.5 percentage of change |
| Raltegravir and Etravirine | Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia) | HDL-cholesterol | 5.4 percentage of change |
| Raltegravir and Etravirine | Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia) | LDL-cholesterol | -4.3 percentage of change |
| Raltegravir and Etravirine | Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia) | fasting glycemia | 0 percentage of change |
Secondary
Evolution of the Calibrated 5-year Framingham Risk Score
The Framingham risk score is expressed as a percentage. Higher scores mean a worse outcome and lower scores mean better outcome. Median percent change expressed as median (interquartile range (IQR))
Time frame: from day 0 to week 48 and at week 96
Population: the number of analyzed participants differs from overall participants due to the Non determined data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Evolution of the Calibrated 5-year Framingham Risk Score | from D0 to week 48 | 1.0 Median percent change as median (IQR) |
| Raltegravir and Etravirine | Evolution of the Calibrated 5-year Framingham Risk Score | from D0 to week 96 | 9.7 Median percent change as median (IQR) |
Secondary
Evolution of the Level of MCP1 From D0 to W48 on Frozen Samples
Time frame: from day 0, to week 48
Population: We evaluated the MCP1 level in 40 women with available samples.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Evolution of the Level of MCP1 From D0 to W48 on Frozen Samples | Premenopausal with mesurable AMH | 3.1 Percentage change |
| Raltegravir and Etravirine | Evolution of the Level of MCP1 From D0 to W48 on Frozen Samples | Premenopausal with reduced ovarian reserve | 3.5 Percentage change |
| Raltegravir and Etravirine | Evolution of the Level of MCP1 From D0 to W48 on Frozen Samples | Post-menopausal | -2.4 Percentage change |
Secondary
Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots
We measured the Anti-mullerian Hormone (AMH) level to evaluate the ovarian reserve (from D0 to W48)
Time frame: from day 0, to week 48
Population: We evaluated the AMH level in 40 women with available samples.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots | Reproductive activity: D0 | 0.172 ng/mL |
| Raltegravir and Etravirine | Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots | Pre-menopausal: D0 | 0.009 ng/mL |
| Raltegravir and Etravirine | Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots | Post-menopausal: D0 | 0.009 ng/mL |
| Raltegravir and Etravirine | Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots | Reproductive activity: W48 | 0.152 ng/mL |
| Raltegravir and Etravirine | Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots | Pre-menopausal: W48 | 0.008 ng/mL |
| Raltegravir and Etravirine | Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots | Post-menopausal: W48 | 0.005 ng/mL |
Secondary
Evolution of Total Cell-associated HIV-DNA
Time frame: from day 0 to week 48 and week 96
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Evolution of Total Cell-associated HIV-DNA | Change from baseline to week 96 | 0 percentage of change |
| Raltegravir and Etravirine | Evolution of Total Cell-associated HIV-DNA | Change from baseline to week 48 | 0 percentage of change |
Secondary
Factors Associated With the Occurrence of Plasma HIV-RNA Viral Load > 50 Copies/mL
Time frame: week 96
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir and Etravirine | Factors Associated With the Occurrence of Plasma HIV-RNA Viral Load > 50 Copies/mL | Age >60 years | 3.7 hazard ratio |
| Raltegravir and Etravirine | Factors Associated With the Occurrence of Plasma HIV-RNA Viral Load > 50 Copies/mL | >=2 glasses/day alcohol consumption | 11.3 hazard ratio |
Secondary
Inflammatory Parameters
• Evolution of the inflammation markers (IL-6hs, sCD14, sCD163, D-Dimers, IP-10, IgG, CRPus and insulin) on frozen plasma aliquots
Time frame: from day 0 to week 96
Population: The number analyzed in one or more rows differs from overall number analyzed due to the missing data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Inflammatory Parameters | IL-6 | 0.8 percentage of change |
| Raltegravir and Etravirine | Inflammatory Parameters | IP-10 | -8.1 percentage of change |
| Raltegravir and Etravirine | Inflammatory Parameters | sCD163 | 0.7 percentage of change |
| Raltegravir and Etravirine | Inflammatory Parameters | sCD14 | -27 percentage of change |
| Raltegravir and Etravirine | Inflammatory Parameters | IgG | 0 percentage of change |
| Raltegravir and Etravirine | Inflammatory Parameters | hsCRP | 0 percentage of change |
| Raltegravir and Etravirine | Inflammatory Parameters | D-Dimer | 16.5 percentage of change |
| Raltegravir and Etravirine | Inflammatory Parameters | Insulin | 4.6 percentage of change |
Secondary
Median Time of Virological Failure
Time between the date of the study treatment initiation and the date of virological failure
Time frame: week 96
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Raltegravir and Etravirine | Median Time of Virological Failure | 96 weeks |
Secondary
Number of Participants Experiencing Adverse Events and Effects
Number of all clinical and biological adverse events effects. Number of grade 3 or 4 clinical and biological adverse events and effects.
Time frame: From day 0 to week 48 and week 96
Population: After week 48, only 156 participants remained on the study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Raltegravir and Etravirine | Number of Participants Experiencing Adverse Events and Effects | Grade 3 or 4 AE: 0-48 week | 15 Participants |
| Raltegravir and Etravirine | Number of Participants Experiencing Adverse Events and Effects | Any AE: 0-48 week | 154 Participants |
| Raltegravir and Etravirine | Number of Participants Experiencing Adverse Events and Effects | Any AE : 48-96 | 108 Participants |
| Raltegravir and Etravirine | Number of Participants Experiencing Adverse Events and Effects | Grade 3 or 4 AE: 48-96 | 11 Participants |
Secondary
Number of Patients With RAL and/or ETR Resistance Mutations Among Those With Virological Failure
Time frame: week 96
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir and Etravirine | Number of Patients With RAL and/or ETR Resistance Mutations Among Those With Virological Failure | 1 participants |
Secondary
Percentage of Participants Compliant With Treatment Program.
The compliance rate was estimated as the number of pills consumed (recorded using the self-reported 90 questionnaire) divided by the number of pills theoretically consumed, classified as low (80%), medium (80%-95%) or high (95%).
Time frame: at week 0, week 48, and week 96
Population: Among 165 analyzed participated, 155 filled the baseline self-reported adherence questionnaire, 146 at week 48 and 136 at week 96
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | low (<80) at W96 | 12 Participants |
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | low (<80) at W0 | 13 Participants |
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | medium (80-95) at W0 | 3 Participants |
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | high (>95) at W0 | 139 Participants |
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | low (<80) at W48 | 7 Participants |
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | medium (80-95) at W48 | 16 Participants |
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | high (>95) at W48 | 123 Participants |
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | medium (80-95) at W96 | 9 Participants |
| Raltegravir and Etravirine | Percentage of Participants Compliant With Treatment Program. | high (>95) at W96 | 115 Participants |
Secondary
Percentage of Participants Reporting a Very Good or an Excellent Quality of Life at Day 0, Weeks 48 and 96
Time frame: day 0 and weeks 48 and 96
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Raltegravir and Etravirine | Percentage of Participants Reporting a Very Good or an Excellent Quality of Life at Day 0, Weeks 48 and 96 | week 96 | 77 Participants |
| Raltegravir and Etravirine | Percentage of Participants Reporting a Very Good or an Excellent Quality of Life at Day 0, Weeks 48 and 96 | day 0 | 63 Participants |
| Raltegravir and Etravirine | Percentage of Participants Reporting a Very Good or an Excellent Quality of Life at Day 0, Weeks 48 and 96 | week 48 | 78 Participants |
Secondary
Percentage of Participants With Detectable Seminal HIV-RNA Viral Load at Week 48
• Assessment of HIV-RNA viral load in human male genital compartment (20 patients) at week 48
Time frame: week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raltegravir and Etravirine | Percentage of Participants With Detectable Seminal HIV-RNA Viral Load at Week 48 | 1 Participants |
Secondary
Percentage of Patients With High Grade of Virological Failure Defined as HIV RNA > 200 Copies/mL
Time frame: weeks 48 and 96
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Percentage of Patients With High Grade of Virological Failure Defined as HIV RNA > 200 Copies/mL | week 48 | 0.6 percentage of participants |
| Raltegravir and Etravirine | Percentage of Patients With High Grade of Virological Failure Defined as HIV RNA > 200 Copies/mL | week 96 | 0 percentage of participants |
Secondary
Percentage of Patients With Therapeutic Success at Week 48 and Week 96
Therapeutic success was defined as the absence of virological failure (i.e. 2 consecutive plasma viral loads (VL) \> 50 copies/mL within 2 to 4 weeks) and the absence of treatment interruption due to adverse event judged by DSMB as related to the study treatment or procedure
Time frame: weeks 48 and 96
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir and Etravirine | Percentage of Patients With Therapeutic Success at Week 48 and Week 96 | at week 48 | 95.1 percentage of participants |
| Raltegravir and Etravirine | Percentage of Patients With Therapeutic Success at Week 48 and Week 96 | at week 96 | 92.7 percentage of participants |
Secondary
Percentage of Patients With Trial Treatment Interruption at Week 48 and Week 96
Time frame: weeks 48 and 96
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir and Etravirine | Percentage of Patients With Trial Treatment Interruption at Week 48 and Week 96 | at week 48 | 4.3 percentage of participant |
| Raltegravir and Etravirine | Percentage of Patients With Trial Treatment Interruption at Week 48 and Week 96 | at week 96 | 6.1 percentage of participant |
Secondary
Percentage of Patients With With Grade Virological Failure (HIV-RNA Plasma VL Between 51 and 200 Copies/mL)
Time frame: weeks 48 and 96
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Raltegravir and Etravirine | Percentage of Patients With With Grade Virological Failure (HIV-RNA Plasma VL Between 51 and 200 Copies/mL) | at week 48 | 0 percentage of participants |
| Raltegravir and Etravirine | Percentage of Patients With With Grade Virological Failure (HIV-RNA Plasma VL Between 51 and 200 Copies/mL) | at week 96 | 0.6 percentage of participants |
Secondary
Percent Change of Renal Function
Percent change of the estimated Glomerular Filtration Rate (eGFR) calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Calculator) formula
Time frame: from day 0 to week 96
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Raltegravir and Etravirine | Percent Change of Renal Function | -0.6 Median percent change, as median (IQR) |
Secondary
Sub-study: Bone Mineral Density
• Evolution of bone mineral density (BMD) measured by DXA scans (DXA scan sub-study, 81 patients) * Lumbar spine BMD, mg/cm2 * Total hip BMD, mg/cm2
Time frame: from day 0, to week 48 and week 96
Population: The number analyzed in one or more rows differs from overall number analyzed due to the missing data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Sub-study: Bone Mineral Density | Lumbar spine BMD from D0 to week 48 | 0.7 percentage of change |
| Raltegravir and Etravirine | Sub-study: Bone Mineral Density | Lumbar spine BMD at week 96 | -1.0 percentage of change |
| Raltegravir and Etravirine | Sub-study: Bone Mineral Density | Total hip BMD from D0 to week 48 | 0.6 percentage of change |
| Raltegravir and Etravirine | Sub-study: Bone Mineral Density | Total hip BMD at week 96 | 0 percentage of change |
Secondary
Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status
BMI, Hip circumference, Waist circumference, waist/hip ratio, Limb fat, Trunk fat, Total fat, Limb lean, Trunk lean, and Total lean
Time frame: from day 0, to week 96
Population: AMH level were evaluated in 40 women with available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Total lean | -1.35 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Total fat | -2.59 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Limb fat | -2.94 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Hip circumference | 7.06 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Trunk fat | -6.90 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Body mass index (BMI) | -0.96 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Trunk lean | -0.79 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Waist circumference | 2.74 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Limb lean | -0.70 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Waist/hip ratio | -3.43 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Waist circumference | 4.20 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Body mass index (BMI) | 5.69 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Hip circumference | 2.80 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Waist/hip ratio | 0.02 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Limb fat | 6.74 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Trunk fat | 18.80 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Total fat | 16.77 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Limb lean | 2.13 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Trunk lean | 5.53 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Total lean | 5.83 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Total fat | 24.39 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Waist circumference | 6.52 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Body mass index (BMI) | 2.07 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Limb lean | -1.44 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Hip circumference | 3.09 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Limb fat | 10.89 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Total lean | -3.01 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Trunk fat | 21.27 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Waist/hip ratio | 1.85 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status | Trunk lean | -3.24 Percentage of change |
Secondary
Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96
Metabolic markers measures are total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides. Inflammatory and innate immune activation markers measures are: IL-6hs, sCD14, sCD163, D-Dimers, IP-10, IgG, hsCRP and Insulin. Ovarian reserve measure is AMH
Time frame: from day 0, to week 96
Population: We evaluated the AMH level in 40 women with available samples
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Total cholesterol | 6.62 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | LDL-cholesterol | 5.52 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | HDL-cholesterol | 18.47 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Triglycerides | 5.59 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | sCD14 | -31.6 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | sCD163 | 10.8 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | hsCRP | 5.7 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | D-dimers | 6.8 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IgG | 0.7 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IL-6hs | 5.9 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IP-10 | -18.3 Percentage of change |
| Raltegravir and Etravirine | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Insulin | -29.2 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Insulin | 30.3 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Total cholesterol | 6.91 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | hsCRP | 31.8 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IgG | 1.8 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | LDL-cholesterol | 5.62 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | sCD163 | 15.9 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IP-10 | 8.2 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | HDL-cholesterol | 27.74 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | D-dimers | 34.8 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | sCD14 | -32.8 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Triglycerides | -38.37 Percentage of change |
| Premenopausal With Reduced Ovarian Reserve | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IL-6hs | -49.9 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Triglycerides | -0.99 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | sCD14 | -18.8 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IL-6hs | -0.9 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | sCD163 | 4.8 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | hsCRP | -31.4 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | D-dimers | 23.1 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IP-10 | -5.4 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Total cholesterol | -11.35 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | LDL-cholesterol | -6.58 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | IgG | -1.2 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | HDL-cholesterol | -4.84 Percentage of change |
| Postmenopausal | Sub-study in Women : Comparison of the Metabolic/Inflammatory Profile in Women According to Their Ovarian Reserve and Menopausal Status at D0 and Its Evolution up to Week 96 | Insulin | 11.4 Percentage of change |