First-Line Treatment for HIV-2

Study Overview
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Brief Summary
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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
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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

Official Title
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A Randomized, Non-comparative, Phase IIb, Unblinded Trial, Evaluating the Efficacy and Safety of Tenofovir-emtricitabine or Lamivudine Plus Zidovudine, Lopinavir/Ritonavir, or Raltegravir, Among ARV-naïve HIV-2 Infected Adult Patients, in West Africa

Conditions
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HIV-2 Infection

Intervention / Treatment
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* Drug: Tenofovir + Emtricitabine or Lamivudine + Zidovudine
* Drug: Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir
* Drug: Tenofovir + Emtricitabine or Lamivudine + Raltegravir


Participation Criteria
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Eligibility Criteria
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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

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A : TDF + FTC (or 3TC) + ZDV<br>Tenofovir + Emtricitabine or Lamivudine + Zidovudine | Drug: Tenofovir + Emtricitabine or Lamivudine + Zidovudine<br>* 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)<br>* Other names: TDF+FTC (or 3TC) + AZT;|
| Experimental: TDF+FTC (or 3TC) +LPV/r<br>Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir | Drug: Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir<br>* 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)<br>* Other names: TDF +FTC (or 3TC) +LPV/r;|
| Experimental: Arm C : TDF +FTC (or 3TC) + RAL<br>Tenofovir + Emtricitabine or Lamivudine + Raltegravir | Drug: Tenofovir + Emtricitabine or Lamivudine + Raltegravir<br>* 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)<br>* Other names: TDF +FTC (or 3TC) + RAL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall success | 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. | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic failure | The percentage of patients in treatment failure defined by : death or 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 a plasma HIV-2 RNA viral load of > or =50 copies/ml or the occurrence of an AIDS defining event (excluding tuberculosis). | 24 weeks | 
| Therapeutic failure | The percentage of patients in treatment failure defined by : death or 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 W0 and W24 (or W48) for patients with baseline CD4 > 500 cellules/mm3 or a plasma HIV-2 RNA viral load of > or = 50 copies/ml or the occurrence of an AIDS defining event (excluding tuberculosis). | 48 weeks | 
| Incidence and type of severe clinical or biological severe adverse events per arm | Incidence and type of severe clinical or biological severe adverse event (grade 3 or 4) | between Week 0 and Week 96 | 
| The clinical progression | The incidence of severe morbidity, defined as: AIDS morbidity, non-AIDS cancer, severe non-AIDS bacterial disease, or any disease leading to death | between Week 0 and Week 96 | 
| The evolution of CD4 counts | Evolution of the absolute and percentage CD4 counts during follow-up | between Week 0 and Week 96 | 
| The evolution of plasma HIV-2 RNA load | Evolution of the plasma viral load during follow-up | between at W0 and W96 | 
| The observance of antiretroviral treatment | To describe the antiretroviral possession ratio and assessment of compliance by questionnaire | between W0 and W96 | 
| The resistance mutations profile | Description of new resistance mutations profiles in cases of treatment failure | Weeks 96 | 
| The evolution of the HIV-2 DNA titers in PBMC | To describe the evolution the HIV-2 DNA titers in PBMC | between Week 0 and Week 96 | 
| The frequency of treatment switches and discontinuations | The frequency of modifications and discontinuations of treatment per arm | between Week 0 and Week 96 | 
| To model the long-term survival and cost-effectiveness ratio | The probability of survival and the incremental cost-effectiveness of these three treatment regimens | Weeks 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Africa, Antiretroviral Treatment, HIV-2, firsts line ART, Adults