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AzTrials

HIV InfectionsPhase 3NCT04867083

Dual Therapy in HIV Patients in 4 Days a Week Versus 7 Days a Week

A Phase 3 study testing ARV bitherapie in people with HIV Infections, run by ANRS, Emerging Infectious Diseases at 38 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48 the non inferiority of antiretroviral dual therapy taken 4 consecutive days per week versus antiretroviral dual therapy 7/7 days per week in HIV-1 infected patients with controlled viral load under… Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
HIV Infections
What is being tested?
ARV bitherapie
Could I receive a placebo?
No, everyone receives an active treatment
How many people
440 participants
Where
38 sitesin 2 countries
Study dates
21 Jun 2021to Jul 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HIV-1 infection, coinfection HIV-1/HIV-2 possible
  • Age≥18 years old
  • Current dual therapy unchanged for the last 6 months with Dolutegravir/ Lamivudine or Dolutegravir / Rilpivirine or Darunavir/r / Lamivudine
  • If a genotype is available in the patient medical history; virus must be susceptible to all on going dual therapy. If no ARN genotype available, the patients can be included in the study
  • Viral load (VL) < 50 c/mL in the past twelve months, with at least 3 VL measurements including screening; only one blip < 200 c/mL is authorized in the 6-12 previous months
  • CD4 T cells > 250/mm3 at W-4
Show all 14Show fewer
  • Estimated glomerular filtration rate > 60 mL/min (CKD-EPI method)
  • AST et ALT < 3N
  • Haemoglobin > 10 g/dL
  • Platelets > 100 000/mm3
  • For women of childbearing age, negative pregnancy plasmatic test at W-4 and agree to use efficacy contraception during the study
  • Commitment to use condom prevention and protection during sexual intercourse for the duration of the trial.
  • Social security system coverage (including State Medical Aid-AME, if EC approves it)
  • Informed consent form signed

Who cannot join

  • Infection by HIV-2
  • Chronic and active Viral B Hepatitis with positive antigen HBs
  • Chronic and active Viral C Hepatitis with treatment expected in the next 48 weeks
  • Concomitant treatment using interferon, interleukins, any other immune-therapy or chemotherapy, antivitamin K+ with co-treatment by booster
  • Concomitant prophylactic or curative treatment for an opportunistic infection
  • All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with study protocol compliance, observance and/or study treatment tolerance
  • Pregnant or breast feeding women
  • Subjects under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship

Trial locations and contacts

38 sites in 2 countries.

Karine AMAT contact

0140256352 ext. 33

karine.amat@imea.fr

Aida BENALYCHERIF contact

0140256365 ext. 33

aida.benalycherif@imea.fr

38 sites in 2 countries

France37 sites, 37 recruiting

  • Centre hospitalier Victor Dupouy/Service d'Hématologie-Unité d'Immunologie

    Argenteuil, 95107

    Fabienne CABY

    Recruiting

  • Hôpital Avicenne/Service des Maladies Infectieuses et tropicales

    Bobigny, 93009

    Olivier BOUCHAUD

    Recruiting

  • Hôpital Saint André/Service HDJ Maladies Infectieuses

    Bordeaux, 33075

    Philippe MORLAT

    Recruiting

  • Hôpital Pellegrin/Service des Maladies Infectieuses et Tropicales

    Bordeaux, 33076

    Didier NEAU

    Recruiting

  • Hôpital Côte de Nacre/Service des Maladies Infectieuses

    Caen, 14033

    Renaud VERDON

    Recruiting

  • Hôpital Louis Pasteur/Service des Maladies Infectieuses

    Chartres, Le Coudray, 28630

    Juliana DARASTEANU

    Recruiting

  • Hôpital Antoine Béclère/Service d'Immunologie Clinique et Médecine Interne

    Clamart, 92141

    Sophie ABGRALL

    Recruiting

  • Centre Hospitalier Sud-Francilien/Service d'Hématologie

    Corbeil-Essonnes, 91106

    Amélie CHABROL

    Recruiting

  • Hôpital François Mitterrand/Service des Maladies Infectieuses

    Dijon, 21079

    Lionel PIROTH

    Recruiting

  • Hôpital Raymond Poincaré/Service des Maladies Infectieuses

    Garches, 92380

    Pierre DE TRUCHIS

    Recruiting

  • CHD de La Roche sur Yon/Service de Médecine Interne

    La Roche-sur-Yon, 85925

    Olivier BOLLENGIER-STRAGIER

    Recruiting

  • Hôpital Franco-Britannique-Fondation Cognacq-Jay

    Levallois-Perret, 92300

    Gilles FORCE

    Recruiting

  • CHU Dupuytren 1/Service des Maladies Infectieuses et Tropicales

    Limoges, 87042

    Claire GENET

    Recruiting

  • Hôpital de la Croix Rousse/Service des Maladies Infectieuses

    Lyon, 69317

    Patrick MIAILHES

    Recruiting

  • Hôpital Sainte Marguerite/Service d'Immuno-Hématologie Clinique

    Marseille, 13274

    Olivia ZAEGEL-FAUCHER

    Recruiting

  • Hôpital Européen/Consultation de Médecine Interne et Maladies Infectieuses

    Marseille, 13331

    Christina PSOMAS

    Recruiting

  • Hôpital Gui de Chauliac/Service des Maladies Infectieuses

    Montpellier, 34295

    Jacques REYNES

    Recruiting

  • Hôpital de l'Hôtel Dieu/Service des Maladies Infectieuses

    Nantes, 44093

    Clothilde ALLAVENA

    Recruiting

  • Hôpital de l'Archet/Service des Maladies Infectieuses

    Nice, 06202

    Vanessa RIO

    Recruiting

  • Hôpital Bichat/Service des Maladies Infectieuses

    Paris, 75018

    Roland LANDMAN

    Recruiting

  • Hôpital Hôtel Dieu/Service d'Immunologie Clinique

    Paris, 75181

    Juliette PAVIE

    Recruiting

  • Hôpital Hôtel Dieu/Unité fonctionnelle de Pathologie Infectieuse

    Paris, 75181

    Dominique SALMON-CERON

    Recruiting

  • Hôpital Lariboisière/Service de Médecine Interne

    Paris, 75475

    Myriam DIEMER

    Recruiting

  • Hôpital Saint Louis/Service des Maladies Infectieuses

    Paris, 75475

    Nathalie DE CASTRO

    Recruiting

  • Hôpital Saint Antoine/Service des Maladies Infectieuses

    Paris, 75571

    Karine LACOMBE

    Recruiting

  • Hôpital Pitié-Salpêtrière/Service des Maladies Infectieuses

    Paris, 75651

    Christine KATLAMA

    Recruiting

  • Hôpital Necker/Service des Maladies Infectieuses

    Paris, 75743

    Claudine DUVIVIER

    Recruiting

  • Hôpital Tenon/Service des Maladies Infectieuses

    Paris, 75970

    Gilles PIALOUX

    Recruiting

  • Centre hospitalier de Poissy/Service des Maladies Infectieuses

    Poissy, 78300

    Benoit CAZENAVE

    Recruiting

  • Centre Hospitalier René Dubos/Service de Dermatologie

    Pontoise, 95301

    Laurent BLUM

    Recruiting

  • Hôpital Robert DEBRE/Service des maladies infectieuses

    Reims, 51092

    Firouzé BANI-SADR

    Not yet recruiting

  • Hôpital Delafontaine/Service des Maladies Infectieuses

    Saint-Denis, 93205

    Marie-Aude KHUONG-JOSSES

    Recruiting

  • Hôpital Civil/Service Le Trait D'union UF 2066

    Strasbourg, 67091

    David REY

    Recruiting

  • Hôpital Foch/Service de Médecine Interne

    Suresnes, 92151

    David ZUCMAN

    Recruiting

  • Hôpital Purpan/Service des Maladies Infectieuses

    Toulouse, 31059

    Pierre DELOBEL

    Recruiting

  • Hôpital Gustave Dron/Service des Maladies Infectieuses

    Tourcoing, 59208

    Olivier ROBINEAU

    Recruiting

  • Hôpital Bretonneau/Service des Maladies Infectieuses

    Tours, 37044

    Louis BERNARD

    Recruiting

Other trials in France

Martinique1 site, 1 recruiting

  • Hôpital Pierre Zobda-Quitman/Service de Médecine Interne

    Fort-de-France, 97261

    André CABIE

    Recruiting

Other trials in Martinique

About this study

Official title: Randomized, Open-label and Multicentric Trial Evaluating the Non-inferiority of Antiretroviral Dual Therapy Taken 4 Consecutive Days Per Week Versus Antiretroviral Dual Therapy 7/7 Days Per Week in HIV-1 Infected Patients With Controlled Viral Load Under Antiretroviral Dual Therapy

The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48 the non inferiority of antiretroviral dual therapy taken 4 consecutive days per week versus antiretroviral dual therapy 7/7 days per week in HIV-1 infected patients with controlled viral load under antiretroviral dual therapy.

Read the detailed description

Open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48 the non-inferiority of antiretroviral dual therapy taken 4 consecutive days a week versus dual therapy taken 7 days a week, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral dual therapy since 4 months. The non-inferiority margin (delta) is 5%. The randomization will be stratified according to the family of the dual therapy at the moment of the inclusion and according to the participation of the substudy or not.

The sample size calculation assumes that the true difference in efficacy between the two arms is zero and that the overall response rate is 97% at week 48. A total of 440 patients (220 per arm) is required to provide 80% power to demonstrate non-inferior efficacy for the 4/7 strategy, compared to the daily dual therapy (7/7), with a two-sided significance level of 5% and a non-inferiority margin (delta) of -5%.

Conditions
HIV Infections
Being tested
ARV bitherapie
Keywords
bitherapy, treatment discontinution, 4 days per week
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARV bitherapieDrug

    1. Dolutégravir 50mg / Lamivudine 300mg per day
    2. Dolutégravir 50mg / Rilpivirine 25mg per day
    3. Darunavir/r 800mg/100mg / Lamivudine 300mg per day
Study groups in NCT04867083
Study groupRoleWhat they receive
Arm 1: 4 days/7Experimental4 days/7 Patients included in this arm will take their ARV treatment 4 consecutive days per week during 48 weeks.
Receives: Drug: ARV bitherapie
Arm 2: 7 days/7Active comparatorPatients included in this arm will take their ARV treatment 7 days per week during 48 weeks
Receives: Drug: ARV bitherapie

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients with virological failure at Week 48.

    The virological failure is defined by 2 successive viral loads >50 c/mL at 2 to 4 weeks apart or a viral load > 50 c/ml with a definitive stop of the study follow-up or the study strategy

    Measured: Week 48

Secondary outcomes (16)

  1. Proportion of participants with therapeutic success until Week 48

    Measured: Week 48

  2. Percentage of participants with at least one episode of "blip"

    viral load >50 copies/mL followed by a control value ≤ 50 cp/mL

    Measured: Week 0 to Week48

  3. Percentage of participants with a viral load signal detected

    Measured: Week 0 to Week 48

  4. Evolution of ultrasensitive viral load and total DNA in the PBMC at W0 and W48

    immuno-virological sub-study

    Measured: Week 0 and Week 48

  5. Proportion of participants with acquisition of drugs resistance mutations in case of virological failure detected by Sanger and by NGS

    Measured: Week 0 to Week 48

  6. Description of selected mutations at the virological failure

    Measured: Week 0 to Week 48

  7. Frequency of minority resistant variants archived in DNA at W0 and their impact on virological failure (2 consecutive VL> 50 copies / mL) and on the acquisition of drugs resistance mutations

    Measured: Week 0

  8. Frequency of grade 3 or more adverse events, adverse effects, drug-modifying adverse events, drug-related adverse events and serious adverse events (SAE)

    Measured: Week 0 to Week 48

  9. Evolution of T CD4 and CD8 cells count, and CD4/CD8 ratio

    Measured: Week-4 to Week 48

  10. Evolution of fasting metabolic parameters (total cholesterol total, LDL-C, HDL-C, Triglycerides and glycemia) until W0 and W48

    Measured: Week 0 to Week 48

  11. Evolution of weight between Week 0 and Week 48

    Measured: Week 0 and Week 48

  12. Evolution of inflammation serum parameters

    immuno-virological sub-study- (sCD14, sCD163, IP-10, CRPus, IL-6, D-dimers, sTNFR1, sTNFR2) from W0 to W24 and W48

    Measured: Week 0 to Week 24 and Week 48

  13. Evolution of semen viral load at Week 0, Week 24 and Week 48

    Sub-study

    Measured: Week 0-Week 24 and Week 48

  14. Description and comparison of plasmatic concentrations of antiretroviral agents between the 2 groups at ON and OFF period

    Measured: Week 0-Week 8-Week 24-Week 48

  15. Evaluation of the adherence by self-reported questionnaire

    Measured: At Week 0, Week 8, Week 24, Week 36 and Week 48-the evaluation will be done after analysis of all the points

  16. Evolution of the quality of life by self-reported questionnaire

    Measured: Week-4 to Week 48-the evaluation will be done after analysis of all the points

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2021
  2. Study start21 Jun 2021
  3. Primary completionJul 2023 (estimated)
  4. Study completionJul 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open-label, multicenter, prospective, randomized trial in 2 parallel groups
Masking
None (open label)
Enrolment
440 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04867083
Sponsor's protocol ID
ANRS 177 DUETTO
Other IDs
2020-003951-13
Status last verified
Nov 2021
First submitted
20 Apr 2021
Last updated
8 Nov 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Fischer M, Hafner R, Schneider C, Trkola A, Joos B, Joller H, Hirschel B, Weber R, Gunthard HF; Swiss HIV Cohort Study. HIV RNA in plasma rebounds within days during structured treatment interruptions. AIDS. 2003 Jan 24;17(2):195-9. doi: 10.1097/00002030-200301240-00009.

    PubMed 12545079

  • Vergis EN, Paterson DL, Wagener MM, Swindells S, Singh N. Dyslipidaemia in HIV-infected patients: association with adherence to potent antiretroviral therapy. Int J STD AIDS. 2001 Jul;12(7):463-8. doi: 10.1258/0956462011923507.

    PubMed 11394983

  • Magalhaes MG, Greenberg B, Hansen H, Glick M. Comorbidities in older patients with HIV: a retrospective study. J Am Dent Assoc. 2007 Nov;138(11):1468-75. doi: 10.14219/jada.archive.2007.0083.

    PubMed 17974644

  • Ananworanich J, Nuesch R, Cote HC, Kerr SJ, Hill A, Jupimai T, Laopraynak N, Saenawat S, Ruxrungtham K, Hirschel B. Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine--a Staccato trial substudy. J Antimicrob Chemother. 2008 Jun;61(6):1340-3. doi: 10.1093/jac/dkn097. Epub 2008 Mar 12.

    PubMed 18339636

  • Ferry JA, Sohani AR, Longtine JA, Schwartz RA, Harris NL. HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma and HHV8-positive intravascular large B-cell lymphoma. Mod Pathol. 2009 May;22(5):618-26. doi: 10.1038/modpathol.2009.36. Epub 2009 Mar 13.

    PubMed 19287457

  • Ho JE, Hsue PY. Cardiovascular manifestations of HIV infection. Heart. 2009 Jul;95(14):1193-202. doi: 10.1136/hrt.2008.161463. No abstract available.

    PubMed 19564432

  • Edelman EJ, Gordon KS, Glover J, McNicholl IR, Fiellin DA, Justice AC. The next therapeutic challenge in HIV: polypharmacy. Drugs Aging. 2013 Aug;30(8):613-28. doi: 10.1007/s40266-013-0093-9.

    PubMed 23740523

  • Flandre P, Raffi F, Descamps D, Calvez V, Peytavin G, Meiffredy V, Harel M, Hazebrouck S, Pialoux G, Aboulker JP, Brun Vezinet F. Final analysis of the Trilege induction-maintenance trial: results at 18 months. AIDS. 2002 Mar 8;16(4):561-8. doi: 10.1097/00002030-200203080-00007.

    PubMed 11872999

  • Bowersox J. ACTG 343: three drugs better than two for maintaining HIV suppression. NIAID AIDS Agenda. 1998 Mar:1-2, 10-1.

    PubMed 11365088

  • Arribas JR, Girard PM, Landman R, Pich J, Mallolas J, Martinez-Rebollar M, Zamora FX, Estrada V, Crespo M, Podzamczer D, Portilla J, Dronda F, Iribarren JA, Domingo P, Pulido F, Montero M, Knobel H, Cabie A, Weiss L, Gatell JM; OLE/RIS-EST13 Study Group. Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015 Jul;15(7):785-92. doi: 10.1016/S1473-3099(15)00096-1. Epub 2015 Jun 7.

    PubMed 26062880

  • Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suarez-Lozano I, Riera M, Estebanez M, Palacios R, Sanz-Moreno J, Troya J, Marino A, Antela A, Navarro J, Esteban H, Moreno S; GeSIDA 7011 Study Group. Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study). J Antimicrob Chemother. 2017 Jan;72(1):246-253. doi: 10.1093/jac/dkw379. Epub 2016 Sep 13.

    PubMed 27629070

  • Di Giambenedetto S, Fabbiani M, Quiros Roldan E, Latini A, D'Ettorre G, Antinori A, Castagna A, Orofino G, Francisci D, Chinello P, Madeddu G, Grima P, Rusconi S, Di Pietro M, Mondi A, Ciccarelli N, Borghetti A, Foca E, Colafigli M, De Luca A, Cauda R; Atlas-M Study Group. Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M). J Antimicrob Chemother. 2017 Apr 1;72(4):1163-1171. doi: 10.1093/jac/dkw557.

    PubMed 28093483

  • Pulido F, Ribera E, Lagarde M, Perez-Valero I, Palacios R, Iribarren JA, Payeras A, Domingo P, Sanz J, Cervero M, Curran A, Rodriguez-Gomez FJ, Tellez MJ, Ryan P, Barrufet P, Knobel H, Rivero A, Alejos B, Yllescas M, Arribas JR; DUAL-GESIDA-8014-RIS-EST45 Study Group. Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial. Clin Infect Dis. 2017 Nov 29;65(12):2112-2118. doi: 10.1093/cid/cix734.

    PubMed 29020293

  • Llibre JM, Hung CC, Brinson C, Castelli F, Girard PM, Kahl LP, Blair EA, Angelis K, Wynne B, Vandermeulen K, Underwood M, Smith K, Gartland M, Aboud M. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018 Mar 3;391(10123):839-849. doi: 10.1016/S0140-6736(17)33095-7. Epub 2018 Jan 6.

    PubMed 29310899

  • Katlama C, Assoumou L, Valantin MA, Soulie C, Martinez E, Beniguel L, Bouchaud O, Raffi F, Molina JM, Fellahi S, Peytavin G, Marcelin AG, Kolta S, Capeau J, Gibowski S, Cardon F, Reynes J, Costagliola D; members of the ANRS 163 ETRAL study. Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study. J Antimicrob Chemother. 2019 Sep 1;74(9):2742-2751. doi: 10.1093/jac/dkz224.

    PubMed 31269208

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ARV bitherapie in people with HIV Infections, run by ANRS, Emerging Infectious Diseases at 38 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in France, Martinique. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Karine AMAT (0140256352 ext. 33, karine.amat@imea.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients with virological failure at Week 48. (time frame: Week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04867083, which also lists 33 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2021.

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