Third Line Antiretroviral Treatment Optimization in Sub-Saharan Africa

Study Overview
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Brief Summary
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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
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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: The efficacy (and associated factors) at 12 weeks of an intensive 3-months adherence reinfrocement phase; 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) ; 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

Official Title
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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.

Conditions
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HIV Infection

Intervention / Treatment
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* Behavioral: adherence reinforcement
* Drug: Antiretroviral Therapy Darunavir/r + Raltegravir + 2 NRTIs (as chosen by the investigators)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adherence reinforcement before switch to 3rd-line ART<br> | Behavioral: adherence reinforcement<br>* Directly observed treatment at home (family or relatives DOT); pillboxes; phone calls; SMS; home visits; adherence reinforcement sessions by trained health workers.<br>Drug: Antiretroviral Therapy Darunavir/r + Raltegravir + 2 NRTIs (as chosen by the investigators)<br>* 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)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Third line ART, Africa, Antiretroviral Treatment, Adherence reinforcement, Second line ART, Virologic failure, Adults