HIV disease MedDRA version: 20.1 Level: LLT Classification code 10020160 Term: HIV disease System Organ Class: 100000004862
Conditions
Interventions
Trade Name: ISENTRESS
Product Name: Isentress
Product Code: J05AX08
Pharmaceutical Form: Tablet
Trade Name: Pifeltro
Product Name: Pifeltro
Product Code: J05AR24
Pharmaceutical Form: Tablet
Sponsors
Centre de Recherche et d’Etudes sur la Pathologie Tropicale et le Sida (CREPATS)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age = 18 years • Patients with HIV-1 documented infection • CD4 = 200/mm3 • On stable combined ART regimen with at least 2 drugs for at least 6 months • HIV-RNA plasma VL = 50 copies/mL during the last 12 months prior to screening visit (W-6/W-4), documented by at least 2 time-points with no more than one blip (defined as one HIV-RNA plasma VL between 51 and 200 copies/mL followed by one HIV-RNA plasma VL = 50 copies/mL) • Naive to doravirine • Absence of resistance to doravirine* and/or raltegravir**(see list mutations below) - on all HIV-genotypes with available RT and integrase gene sequences allowing resistance interpretation in case of previous virological failure - or on DNA genotype performed at screening if HIV genotype is not available in case of prior virological failure. • Signed informed consent form. • Patient affiliated to a social insurance regimen. For French patients only: subject enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme). *Mutations associated to doravirine resistance are: V106A/M, Y188L, G190E/S, M230L, F227C, at least 2 among: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y . **Mutations associated to raltegravir resistance are: T66A/K, E92Q, G118R, F121Y, G140A/S Y143A/C/G/H/R/S, Q148E/G/H/K/R, V151L, N155H/S/T, E157Q, S230R, R263K, L74 F/I + V75I. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Absence of RT and INI HIV sequence available (past genotypes or failure of amplification of DNA at screening) • HBV co-infection • Hemoglobin <9 g/dL • Platelets <80,000/mm3 • Creatinine clearance <60 mL/min (MDRD) • AST or ALT =5N • Concomitant DAA for anti-HCV therapy • Any severe concomitant illness • Any drug with potential drug-drug interaction with doravirine • Concomitant treatment using interferon, interleukins or any other immune-therapy 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 "sauvegarde de justice" (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 |
|---|---|
| Main Objective: To evaluate the virological efficacy at week 48 of once daily doravirine plus raltegravir dual therapy in HIV-1-infected patients suppressed on ART ;Secondary Objective: •Virological efficacy of the doravirine plus raltegravir dual therapy •To assess the proportion of patients in therapeutic success up to week 48 and week 96 •Resistance profile in case of virological failure •Evolution of CD4 and CD8 T-cells, and CD4/CD8 ratio •Clinical and biological tolerability of the doravirine plus raltegravir dual therapy •Quality of life questionnaire •Observance questionnaire •Evolution of HIV-reservoir (Whole blood will be collected at D0, W48 and W96) •Evolution of the inflammation markers (on frozen plasma/serum samples at D0, W48 and W96 (analysis not yet funded) ;Primary end point(s): The proportion of patients with virological failure before or at week 48. Protocol virological failure is defined as two pVL>50 copies/mL two weeks apart. ;Timepoint(s) of evaluation of this end point: at week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of patients maintaining viral suppression (pVL 50 copies/mL followed by a second measurement <50 copies/mL) • Resistance profile in case of protocol defined virological failure (PDVF) • Proportion of patients with acquired resistance mutation among those with PDVF • Frequency of grade 3 and 4 events • Quality of life assessed by self-questionnaire at screening, D0, W24, W48, W72, W96 • Observance assessed by self-questionnaire at D0, W24, W48, W96 • Evolution of total cell HIV-DNA in PBMC from D0 to W48 and W96 • Evolution of inflammation markers from D0 to W48 and W96 (not yet funded) • To assess HIV-RNA viral load and Cmin (Minimal Drug Concentration) of doravirine/raltegravir at D0 and W48 in human male genital compartment (Seminal sub-study, 30 patients) • Evaluate the maintenance of HIV viral suppression as well as changes in neuronal injury and inflammatory markers in cerebrospinal fluid (CSF) at D0 and W48 (CSF sub-study, 15 patients included in the Spanish centers) (sub-study not yet funded) ;Timepoint(s) of evaluation of this end point: 96 weeks | — |
Countries
France, Italy
Contacts
Public ContactPr Christine KATLAMA
pitie salpetriere hospital
Outcome results
None listed