Third Line Antiretroviral Treatment Optimization in Sub-Saharan Africa

HIV Infection Clinical Trial

— THILAO  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02025868
• Other study ID #: ANRS 12269 THILAO
• Status: Active, not recruiting
• Phase: Phase 2
• First received: December 30, 2013
• Last updated: February 16, 2017
• Start date: March 2013
• Est. completion date: May 2017

Study information

• Verified date: February 2017
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 201
• Est. completion date: May 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

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)

Locations

Country	Name	City	State
Burkina Faso	CHU Sourô Sanou	Bobo-Dioulasso
Burkina Faso	CHU Yalgado Ouedraogo	Ouagadougou
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)	Abidjan
Mali	Centre d'Ecoute, de Soins, d'Animation et de Conseils (CESAC)	Bamako
Mali	CHU Point G	Bamako
Senegal	CHU Fann	Dakar

Sponsors (1)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Countries where clinical trial is conducted

Burkina Faso,  Côte D'Ivoire,  Mali,  Senegal, 

Outcome

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

External Links

•   Link
•   Sponsor site