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
Condition: HIV-1 Infection
Intervention: raltegravir and etravirine
Intervention description: 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.
Intervention MeSH terms: Raltegravir Potassium; Etravirine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 170.0
Sex: All
Minimum age: 45 Years
Healthy volunteers: No
Keywords: Raltegravir; Etravirine; aged, 45 and over; Viral load; Efficacy; Safety

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 < 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