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

ANRS, Emerging Infectious Diseases

Status and phase

Completed

Phase 2

Conditions

HIV-1 Infection

Treatments

Drug: raltegravir and etravirine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02212379

2014-000828-24

ANRS 163 ETRAL (Other Identifier)

Details and patient eligibility

About

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.

Enrollment

170 patients

Sex

All

Ages

45+ years old

Volunteers

No Healthy Volunteers

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