Phase 2
N=165
Capacity of the Dual Combination Raltegravir/Etravirine to Maintain Virological Success in HIV-1 Infected Patients of at Least 45 Years of Age- ANRS 163 ETRAL
HIV-1 Infection
Bottom Line
View on ClinicalTrials.gov: NCT02212379 ↗Enrolled (actual)
165
Serious AEs
15.8%
Results posted
Feb 2021
Primary outcome: Primary: Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96 — 99.4; 98.7 percentage of participant
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- raltegravir and etravirine (Drug)
- Age
- Adult, Older Adult · 45+ yrs
- Sex
- All
- Sponsor
- ANRS, Emerging Infectious Diseases
- Primary completion
- Oct 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Successful Virological Suppression at Weeks 48 and 96 |
99.4; 98.7 | — |
| SECONDARY Percentage of Patients With Therapeutic Success at Week 48 and Week 96 |
95.1; 92.7 | — |
| SECONDARY Percentage of Patients With Trial Treatment Interruption at Week 48 and Week 96 |
4.3; 6.1 | — |
| SECONDARY Percentage of Patients With With Grade Virological Failure (HIV-RNA Plasma VL Between 51 and 200 Copies/mL) |
0; 0.6 | — |
| SECONDARY Median Time of Virological Failure |
96 | — |
| SECONDARY Percentage of Patients With High Grade of Virological Failure Defined as HIV RNA > 200 Copies/mL |
0.6; 0 | — |
| SECONDARY Number of Patients With RAL and/or ETR Resistance Mutations Among Those With Virological Failure |
1 | — |
| SECONDARY Factors Associated With the Occurrence of Plasma HIV-RNA Viral Load > 50 Copies/mL |
3.7; 11.3 | — |
| SECONDARY Evolution of Total Cell-associated HIV-DNA |
0; 0 | — |
| SECONDARY Evolution of CD4+, CD8+ T Cells Counts and CD4/CD8 Ratio |
1.1; -1.8; 5.7; 5.0; -5.2; 7.4 | — |
| SECONDARY Number of Participants Experiencing Adverse Events and Effects |
154; 15; 108; 11 | — |
| SECONDARY Evolution of Metabolic Parameters (Fasting Triglycerides, Total Cholesterol, HDL-cholesterol, LDL-cholesterol and Fasting Glycemia) |
-18.8; -0.5; 5.4; -4.3; 0 | — |
| SECONDARY Evolution of the Calibrated 5-year Framingham Risk Score |
1.0; 9.7 | — |
| SECONDARY Percent Change of Renal Function |
-0.6 | — |
| SECONDARY Evolution of Body Fat Distribution From Day 0 to W96 (DXA Scan Sub-study, 80 Patients) |
12.2; 11.6; 12.2 | — |
| SECONDARY Sub-study: Bone Mineral Density |
0.7; -1.0; 0.6; 0 | — |
| SECONDARY Percentage of Participants With Detectable Seminal HIV-RNA Viral Load at Week 48 |
1 | — |
| SECONDARY Inflammatory Parameters |
0.8; -8.1; 0.7; -27; 0; 0 | — |
| SECONDARY Percentage of Participants Reporting a Very Good or an Excellent Quality of Life at Day 0, Weeks 48 and 96 |
63; 78; 77 | — |
| SECONDARY Percentage of Participants Compliant With Treatment Program. |
13; 3; 139; 7; 16; 123 | — |
| SECONDARY Evolution of the Ovarian Reserve From D0 to W48 Measured by AMH on Frozen Aliquots |
0.172; 0.009; 0.009; 0.152; 0.008; 0.005 | — |
| SECONDARY Evolution of the Level of MCP1 From D0 to W48 on Frozen Samples |
3.1; 3.5; -2.4 | — |
| 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 |
6.62; 6.91; -11.35; 5.52; 5.62; -6.58 | — |
| SECONDARY Sub-study in Women : Comparison of the Evolution Fat Distribution Measured by DXA Scan and Body Weight According to AMH Status |
-0.96; 5.69; 2.07; 7.06; 2.80; 3.09 | — |
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.
Eligibility Criteria
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 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
Data sourced from ClinicalTrials.gov (NCT02212379). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.