HIV-2 Infection
Conditions
Keywords
Africa, Antiretroviral Treatment, HIV-2, firsts line ART, Adults
Brief summary
FIT-2 is a multi-country, phase IIb, randomized, non-comparative study, carried out in West Africa (Côte d'Ivoire, Burkina Faso, Senegal, Togo). ARV-naïve HIV-2 infected adult patients will be recruited and followed during 96 weeks. The objective is to evaluate the efficacy and safety of 3 first-line treatments in HIV-2 infected adult patients, in West Africa. A treatment will be considered as effective if more than 55% of patients in that arm attain global success at 96 weeks.
Detailed description
Main objective To determine in treatment-naïve HIV-2 infected patients, with CD4 counts above 200 cells/mm3, which of the following three regimens of first line treatment, Tenofovir (TDF), Emtricitabine or lamivudine (FTC or 3TC) plus Zidovudine (ZDV); TDF-FTC (3TC) plus Lopinavir/ritonavir (LPV / r); or TDF-FTC (3TC) plus raltegravir (RAL), will result in an global success rate of \> 55% at week 96. Number of participants : 210 Main outcome : The proportion of patients with global success at W96, defined by survival with a plasma HIV-2 RNA viral load of \<50 copies/ml and the non-occurrence of AIDS classified events (excluding tuberculosis) and the non-occurrence of severe morbidities non-AIDS-defining illness (cardiovascular disease, kidney disease, severe bacterial disease) and a delta of CD4 depending on the initial CD4 count (CD4 delta \> +100cells/mm3 for initial CD4s between 201 and 500 cells/mm3 or delta ≥0 cells/mm3 for initial CD4s \> +500 cells/mm3) Inclusion criteria: * Infection by HIV-2 only; * Age \> or = 18 years; * Naïve for antiretroviral therapy (including antiretroviral treatment in the context of PMTCT except taking a dose of Nevirapine for PMTCT) * CD4 \>200 cells/mm3 * Resident of the city where the study is held or of city suburbs to facilitate participation * Signed informed consent document
Interventions
DRUGTenofovir + Emtricitabine or Lamivudine + Zidovudine
TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + ZDV (Zidovudine 300 mg) 1 tb BID (mornings and evenings orally)
DRUGTenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir
TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + Lop/r (Lopinavir/ritonavir lopinavir 200/50 mg) 2 tbs BID (mornings and evenings orally)
DRUGTenofovir + Emtricitabine or Lamivudine + Raltegravir
TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + RAL (Raltegravir 400 mg) 1 tb BID (mornings and evenings orally)
Sponsors
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Infection by HIV-2 only; * Age \> ou = 18 years; * Naïve for antiretroviral therapy (including antiretroviral treatment in the context of PMTCT except taking a dose of Nevirapine for PMTCT) * CD4 \>200 cells/mm3 * Resident of the city where the study is held or of city suburbs to facilitate participation * Signed informed consent document
Exclusion criteria
* Current participation in any other clinical trial * Presence of opportunistic non-stabilized infections, of any serious or progressive disease, or of any clinical signs consistent with severe disease whose diagnosis is not yet confirmed, such as fever, weight loss, diarrhea or cough not yet explained (non-exhaustive list). * All pathology that leads in daily life to prefer one or the other of the three therapeutic regimens for medical reasons or to change the dosages specified in the test. This includes (but not limited to): * Hemoglobin ≤ 8 g / dL * Neutrophil count \<500 cells/mm3 * Renal impairment with creatinine clearance \<50mL/mn * Blood platelet \<50 000 cells/mm3 * Decompensated heart failure * Hepatic failure Severe (TP\<50% or cytolysis severe (ALAT\> 3x ULN) * Active TB during treatment with rifampicin * Taking drugs that interact with the drugs of the clinical trial (as specified in the SPC) * Pregnancy, breastfeeding or planning to become pregnant during study follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The overall success | 96 weeks | The proportion of patients with global success at W96, defined by survival with a plasma HIV-2 RNA viral load of \<50 copies/ml and the non-occurrence of AIDS classified events (excluding tuberculosis) and the non-occurrence of severe morbidities non-AIDS-defining illness (cardiovascular disease, kidney disease, severe bacterial disease) and a delta of CD4 depending on the initial CD4 count (CD4 delta\> +100cells/mm3 for initial CD4s between 201 and 500 cells/mm3 or delta ≥0 cells/mm3 for initial CD4s \> +500 cells/mm3) A treatment is considered to be effective if the global success is \> 55 % at 96 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and type of severe clinical or biological severe adverse events per arm | between Week 0 and Week 96 | Incidence and type of severe clinical or biological severe adverse event (grade 3 or 4) |
| The clinical progression | between Week 0 and Week 96 | The incidence of severe morbidity, defined as: AIDS morbidity, non-AIDS cancer, severe non-AIDS bacterial disease, or any disease leading to death |
| The evolution of CD4 counts | between Week 0 and Week 96 | Evolution of the absolute and percentage CD4 counts during follow-up |
| The evolution of plasma HIV-2 RNA load | between at W0 and W96 | Evolution of the plasma viral load during follow-up |
| Therapeutic failure | 24 weeks | The percentage of patients in treatment failure defined by : 1. death or 2. a delta ≤0 CD4 cells / mm3 between W2 and W24 (or W48) for patients with baseline CD4 between 201 and 500 cells / mm3 or if % of decrease in CD4 \> 20% between W2 and W24 (or W48) for patients with baseline CD4 \> 500 cellules/mm3 or 3. a plasma HIV-2 RNA viral load of \> or =50 copies/ml or 4. the occurrence of an AIDS defining event (excluding tuberculosis). |
| The resistance mutations profile | Weeks 96 | Description of new resistance mutations profiles in cases of treatment failure |
| The evolution of the HIV-2 DNA titers in PBMC | between Week 0 and Week 96 | To describe the evolution the HIV-2 DNA titers in PBMC |
| The frequency of treatment switches and discontinuations | between Week 0 and Week 96 | The frequency of modifications and discontinuations of treatment per arm |
| To model the long-term survival and cost-effectiveness ratio | Weeks 96 | The probability of survival and the incremental cost-effectiveness of these three treatment regimens |
| The observance of antiretroviral treatment | between W0 and W96 | To describe the antiretroviral possession ratio and assessment of compliance by questionnaire |
Countries
Burkina Faso, Côte d’Ivoire, Senegal, Togo
Outcome results
None listed