Clinical trial NCT02025868: Third Line Antiretroviral Treatment Optimization in Sub-Saharan Africa
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HIV Infection
Keywords: Africa
Antiretroviral Treatment
Adherence reinforcement
Third line ART
Second line ART
Virologic failure
Adults
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2014-01-01
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Virologic efficacy of the adherence reinforcement intervention
timeFrame: Week 12
measure: Persistent virologic efficacy of the adherence reinforcement intervention
timeFrame: Week 64
measure: Virologic efficacy of 3rd-line ART
timeFrame: Week 64
Secondary outcomes:
measure: Immunological efficacy of the adherence reinforcement intervention
timeFrame: Week 12
measure: Immunological efficacy of 3rd-line ART
timeFrame: Week 64
measure: Tolerance of 3rd-line ART drugs
timeFrame: Week 64
measure: Adherence to 3rd-line ART
timeFrame: Week 64
measure: Resistance to 1st and 2nd-line antiretroviral drugs
timeFrame: Week 12
measure: Resistance to 1st, 2nd and 3rd-line antiretroviral drugs
timeFrame: Week 64
measure: Plasma antiretroviral drugs concentration
timeFrame: Week 12
measure: Plasma antiretroviral drugs concentration
timeFrame: Week 64
Other outcomes:
Locations:
city: Bobo-Dioulasso
country: Burkina Faso
facility: CHU Sourô Sanou
city: Ouagadougou
country: Burkina Faso
facility: CHU Yalgado Ouedraogo
city: Abidjan
country: Côte D'Ivoire
facility: Centre de Prise en Charge et de Formation (CePReF), Association ACONDA
city: Abidjan
country: Côte D'Ivoire
facility: Service des Maladies Infectieuses et Tropicales (SMIT)
city: Bamako
country: Mali
facility: Centre d'Ecoute, de Soins, d'Animation et de Conseils (CESAC)
city: Bamako
country: Mali
facility: CHU Point G
city: Dakar
country: Senegal
facility: CHU Fann
Study officials:
affiliation: Service des Maladies Infectieuses et Tropicales, CHU de Treichville, Abidjan, Côte d'Ivoire
name: Serge P. Eholie, MD, MSc, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Médecine et d'Epidémiologie Appliquée - Hôpital Bichat Claude Bernard, Paris, France
name: Roland Landman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inserm 897, University of Bordeaux, France
name: Xavier Anglaret, MD, PhD
role: STUDY_DIRECTOR
affiliation: Infectious Diseases Department, University Hospital Saint Antoine, Paris, France
name: Pierre-Marie Girard, MD, PhD
role: STUDY_CHAIR
References: