HIV-1 INFECTION
Conditions
Interventions
Trade Name: PIFELTRO
Product Name: PIFELTRO (DORAVIRINA)
Product Code: MK-1439
Pharmaceutical Form: Coated tablet
Trade Name: ISENTRESS
Product Name: ISENTRESS (RALTEGRAVIR)
Product Code: MK-0518
Pha
Sponsors
Centre de Recherche et d’Etudes sur la Pathologie Tropical 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
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 immunetherapy 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: To evaluate over 96 weeks: • 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) ;Primary end point(s): The primary endpoint is 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: WEEK 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate over 96 weeks: • 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;Timepoint(s) of evaluation of this end point: WEEK 96 | — |
Countries
France, Italy
Contacts
Public ContactANTONELLA CASTAGNA
IRCCS SAN RAFFAELE HOSPITAL
Outcome results
None listed