Third Line Antiretroviral Threatment Optimization in Sub-Saharan Africa (THILAO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT02025868
First received: December 30, 2013
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

Thilao is a multi-country, phase 2b, non-randomized study, in Burkina Faso, Cote d'Ivoire, Mali and Senegal, West Africa.

HIV-1 adults with 2nd-line ART virologic failure (plasma HIV-1 RNA >1000 copies/ml) will be recruited and followed in two phases:

  • First, a 12-week intentive adherence reinforcement phase, during which patients will continue 2nd-line ART, be seen repeatidly for counseling and educational training on adherence, and be offered the possibility of phone, SMS and home visit contacts with social workers;
  • Second, a 48-week phase, during which:

    • Patients successfully resuppressed at the end of the first phase will continue 2nd-line ART and adherence reinforcement;
    • Patients with persitent virologic failure will switch to a darunavir/r + raltegravir-based 3rd-line ART.

Genotype resistance tests will be performed retrospectively on frozen samples. The main outcome will be the percentage of patients with plasma HIV-1 viral RNA <50 copies/ml at 64 weeks.


Condition Intervention Phase
HIV Infection
Behavioral: adherence reinforcement
Drug: Antiretroviral Therapy Darunavir/r + Raltegravir + 2 NRTIs (as chosen by the investigators)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Systematic "Adherence Intervention" Phase Before Switching to 3rd-line ART in Patients With 2nd-line ART Virologic Failure in Sub-Saharan Africa : a Phase 2b Non-randomized Study.

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Virologic efficacy of the adherence reinforcement intervention [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Proportion of patients with plasma viral load <400 copies/ml at Week 12 and/or with a decrease in plasma viral load >2 log10 copies/ml between inclusion and Week 12

  • Persistent virologic efficacy of the adherence reinforcement intervention [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Proportion of patients with plasma viral load <50 copies/ ml at Week 64 among those who stayed on 2nd-line ART at Week 16

  • Virologic efficacy of 3rd-line ART [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Proportion of patients with HIV-1 plasma viral load <50 copies/ml at Week 64 among those with persistent failure at Week 12 who switched to 3rd-line ART


Secondary Outcome Measures:
  • Immunological efficacy of the adherence reinforcement intervention [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    CD4 count evolution between inclusion and Week 12

  • Immunological efficacy of 3rd-line ART [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    CD4 count evolution between Week12 and Week 64 among patients who switched to 3rd-line ART at Week 16

  • Tolerance of 3rd-line ART drugs [ Time Frame: Week 64 ] [ Designated as safety issue: Yes ]
    Incidence of grade 3-4 adverse events (ANRS grading table) in patients on 3rd-line ART

  • Adherence to 3rd-line ART [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    3rd-line Medication Possession Ratio between Week 16 and Week 64

  • Resistance to 1st and 2nd-line antiretroviral drugs [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Resistance mutations to antiretroviral drugs among patients with virological failure at Week 12

  • Resistance to 1st, 2nd and 3rd-line antiretroviral drugs [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Resistance mutations to antiretroviral drugs among patients with virological failure at Week 64

  • Plasma antiretroviral drugs concentration [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Plasma antiretroviral drugs concentration at Week 12

  • Plasma antiretroviral drugs concentration [ Time Frame: Week 64 ] [ Designated as safety issue: No ]
    Plasma antiretroviral drugs concentration at Week 64


Estimated Enrollment: 200
Study Start Date: March 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adherence reinforcement before switch to 3rd-line ART Behavioral: adherence reinforcement
Directly observed treatment at home (family or relatives DOT); pillboxes; phone calls; SMS; home visits; adherence reinforcement sessions by trained health workers.
Drug: Antiretroviral Therapy Darunavir/r + Raltegravir + 2 NRTIs (as chosen by the investigators)

Second-line ART regimen : ongoing regimen at the time of inclusion will be continued.

Third-line ART regimen : Darunavir/r + Raltegravir + 2 NRTIs (as chosen by the investigators)


Detailed Description:

Main objective

To estimate, in sub-Saharan African HIV-1 infected adults who failed a NNRTI-base first-line ART and then a PI-based second-line ART:

  1. The efficacy (and associated factors) at 12 weeks of an intensive 3-months adherence reinfrocement phase;
  2. In patients who successfully resuppress at 12 weeks: The percentage of patients still with continuing succesfull virologic supression on 2nd-line ART at 64 weeks (and factors associated to success) ;
  3. In patients with persistent failure at 12 weeks : The efficacy (and associated factors) at 64 weeks of a darunavir/r + raltegravir-based 3rd-line regimen.

Number of participants : 200

Main outcome :

  • At 12 weeks : Proportion of patients with a plasma HIV-1 RNA <400 copies/ml and/or with a decrease in plasma HIV-1 RNA >2 log10 copies/ml between inclusion and 12 weeks;
  • At 64 weeks : proportion of patients with a plasma HIV-1 RNA <50 copies/ml.

Inclusion criteria:

  • Age >18 years
  • Documented HIV-1 infection.
  • History of failing a NNRTI-based 1st-line ART
  • Current PI-based 2nd-line ART >6 months
  • Plasma HIV-1 RNA >1000 copies/ml
  • Signed informed consent
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >18 years
  • Documented HIV-1 infection
  • History of failing a NNRTI-based 1st-line ART
  • Current PI-based 2nd-line ART >6 months
  • Plasma HIV-1 RNA >1000 copies/ml
  • Signed informed consent

Exclusion Criteria:

  • HIV-2 infection
  • Any Severe clinical event under exploration
  • History of treatment including darunavir or raltegravir.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02025868

Contacts
Contact: Raoul Desmoryl Moh, MD, PHD +225 07 82 83 79 raoul.moh@pacci.ci
Contact: Aïda Benalcherif +33 (1) 40 25 63 65 aida.benalycherif@gmail.com

Locations
Burkina Faso
CHU Sourô Sanou Recruiting
Bobo-Dioulasso, Burkina Faso
Contact: Adrien B Sawadogo, MD    +22620985255    sawadogoadrien@yahoo.fr   
Contact: Jacques Zoungrana, MD    +22672303821    zojacques@yahoo.fr   
Sub-Investigator: Jacques Zoungrana, MD         
Côte D'Ivoire
Centre de Prise en Charge et de Formation (CePReF), Association ACONDA Recruiting
Abidjan, Côte D'Ivoire
Contact: Eugène Messou, MD, PhD    +22523462551    messou_eugene@yahoo.fr   
Contact: Ama Anzian, MD    +22540185774    amani_anzian@yahoo.fr   
Sub-Investigator: Amani Anzian, MD         
Service des Maladies Infectieuses et Tropicales (SMIT) Recruiting
Abidjan, Côte D'Ivoire
Contact: Emmanuel Bissagnene, MD, Pr    +22521755960    bissagnene@yahoo.fr   
Contact: Frédéric Ello, MD    +22521755960    ellonogboufrdric@yahoo.fr   
Sub-Investigator: Eboumou Gole, MD         
Mali
CHU Point G Not yet recruiting
Bamako, Mali
Contact: Daouda K Minta, MD    +22320229790    douada_minta@yahoo.fr   
Contact: Abdoulaye Traoré, MD    +22320229790    matraore_cmbko@yahoo.fr   
Sub-Investigator: Mahamadou Fomba, MD         
Centre d'Ecoute, de Soins, d'Animation et de Conseils (CESAC) Not yet recruiting
Bamako, Mali
Contact: Mamadou Cissé, MD    +22320236477    madci@yahoo.fr   
Contact: Fodié Diallo, MD    +22366731815    fodie10@yahoo.fr   
Sub-Investigator: Konate Tiefing, MD         
Senegal
CHU Fann Not yet recruiting
Dakar, Senegal
Contact: Moussa Seydi, MD, Pr    +221338231327    seydi_moussa@gmail.com   
Contact: Mouhamadou B Diallo, MD    +221776511773    mamadoubaila@yahoo.fr   
Sub-Investigator: Nogaye Gaye         
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Serge P. Eholie, MD, MSc, Pr Service des Maladies Infectieuses et Tropicales, CHU de Treichville, Abidjan, Côte d'Ivoire
Principal Investigator: Roland Landman, MD Institut de Médecine et d'Epidémiologie Appliquée - Hôpital Bichat Claude Bernard, Paris, France
Study Director: Xavier Anglaret, MD, PhD Inserm 897, University of Bordeaux, France
Study Chair: Pierre-Marie Girard, MD, PhD Infectious Diseases Department, University Hospital Saint Antoine, Paris, France
  More Information

Additional Information:
No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT02025868     History of Changes
Other Study ID Numbers: ANRS 12269 THILAO
Study First Received: December 30, 2013
Last Updated: January 2, 2014
Health Authority: Burkina Faso: Ministère de la santé
Burkina Faso: Ministère de la Recherche Scientifique et de l'Innovation
Burkina Faso: Comité d'Ethique pour la Recherche en Santé
Cote d'Ivoire: Ministère de la Santé et de la Lutte contre le SIDA
Cote d'Ivoire: Comité National d'Ethique et de la Recherche
Mali: Ministère de la santé
Mali: Comité d'Ethique de l'Institut National de Recherche en Santé Publique
Senegal: Ministere de la Sante et de l'Action Sociale
Senegal: Comité National d'Ethique pour la Recherche en Santé

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
Africa
Antiretroviral Treatment
Adherence reinforcement
Third line ART
Second line ART
Virologic failure
Adults

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014