HIV Infection
Conditions
Keywords
Africa, Antiretroviral Treatment, Adherence reinforcement, Third line ART, Second line ART, Virologic failure, Adults
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
Interventions
BEHAVIORALadherence reinforcement
Directly observed treatment at home (family or relatives DOT); pillboxes; phone calls; SMS; home visits; adherence reinforcement sessions by trained health workers.
DRUGAntiretroviral 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)
Sponsors
ANRS, Emerging Infectious Diseases
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Virologic efficacy of the adherence reinforcement intervention | Week 12 | 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 | Week 64 | 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 | Week 64 | 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
| Measure | Time frame | Description |
|---|---|---|
| Adherence to 3rd-line ART | Week 64 | 3rd-line Medication Possession Ratio between Week 16 and Week 64 |
| Resistance to 1st and 2nd-line antiretroviral drugs | Week 12 | Resistance mutations to antiretroviral drugs among patients with virological failure at Week 12 |
| Immunological efficacy of the adherence reinforcement intervention | Week 12 | CD4 count evolution between inclusion and Week 12 |
| Plasma antiretroviral drugs concentration | Week 12 | Plasma antiretroviral drugs concentration at Week 12 |
| Resistance to 1st, 2nd and 3rd-line antiretroviral drugs | Week 64 | Resistance mutations to antiretroviral drugs among patients with virological failure at Week 64 |
| Immunological efficacy of 3rd-line ART | Week 64 | 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 | Week 64 | Incidence of grade 3-4 adverse events (ANRS grading table) in patients on 3rd-line ART |
Countries
Burkina Faso, Côte d’Ivoire, Mali, Senegal
Outcome results
None listed