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

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.

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.

Study Overview

• Status: Unknown
• Conditions: HIV Infection
• Intervention / Treatment: Behavioral: adherence reinforcement; Drug: Antiretroviral Therapy 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

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 2

Contacts and Locations

Study Locations

• Burkina Faso
  • Bobo-Dioulasso, Burkina Faso
    • CHU Souro Sanou
  • Ouagadougou, Burkina Faso
    • CHU Yalgado Ouedraogo
• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire
    • Centre de Prise en Charge et de Formation (CePReF), Association ACONDA
  • Abidjan, Côte D'Ivoire
    • Service des Maladies Infectieuses et Tropicales (SMIT)
• Mali
  • Bamako, Mali
    • Centre d'Ecoute, de Soins, d'Animation et de Conseils (CESAC)
  • Bamako, Mali
    • CHU point G
• Senegal
  • Dakar, Senegal
    • CHU Fann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic efficacy of the adherence reinforcement intervention	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	Week 12
Persistent virologic efficacy of the adherence reinforcement intervention	Proportion of patients with plasma viral load <50 copies/ ml at Week 64 among those who stayed on 2nd-line ART at Week 16	Week 64
Virologic efficacy of 3rd-line ART	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	Week 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological efficacy of the adherence reinforcement intervention	CD4 count evolution between inclusion and Week 12	Week 12
Immunological efficacy of 3rd-line ART	CD4 count evolution between Week12 and Week 64 among patients who switched to 3rd-line ART at Week 16	Week 64
Tolerance of 3rd-line ART drugs	Incidence of grade 3-4 adverse events (ANRS grading table) in patients on 3rd-line ART	Week 64
Adherence to 3rd-line ART	3rd-line Medication Possession Ratio between Week 16 and Week 64	Week 64
Resistance to 1st and 2nd-line antiretroviral drugs	Resistance mutations to antiretroviral drugs among patients with virological failure at Week 12	Week 12
Resistance to 1st, 2nd and 3rd-line antiretroviral drugs	Resistance mutations to antiretroviral drugs among patients with virological failure at Week 64	Week 64
Plasma antiretroviral drugs concentration	Plasma antiretroviral drugs concentration at Week 12	Week 12
Plasma antiretroviral drugs concentration	Plasma antiretroviral drugs concentration at Week 64	Week 64

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Serge P. Eholié, 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 Chair: Pierre-Marie Girard, MD, PhD, Infectious Diseases Department, University Hospital Saint Antoine, Paris, France; Study Director: Xavier Anglaret, MD, PhD, Inserm 897, University of Bordeaux, France

Publications and helpful links

Helpful Links

• Related Info
• Sponsor site

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): August 1, 2016
• Study Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: December 30, 2013
• First Submitted That Met QC Criteria: December 31, 2013
• First Posted (Estimate): January 1, 2014

Study Record Updates

• Last Update Posted (Actual): February 17, 2017
• Last Update Submitted That Met QC Criteria: February 16, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Adults; Africa; Virologic failure; Antiretroviral Treatment; Adherence reinforcement; Third line ART; Second line ART
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Protease Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Darunavir; Anti-Retroviral Agents
• Other Study ID Numbers: ANRS 12269 THILAO