Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients

Study Overview
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Brief Summary
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The HIV-2 is less common ie 1-2 million people in West Africa. HIV-2 does have the same sensitivity to antiretroviral treatment (ART) compared to HIV-1. The ART strategies that are appropriate for the HIV-1 infection are not as effective for HIV-2. Classical triple therapy including PI is less effective for HIV-2. Also, the choice of ARTs in a second line treatment is limited. The first line optimal treatment has to be defined by a prospective and randomized evaluation of other strategies. The primary endpoint will be adapted to the specificity of the HIV-2 infection. The 1st step is to define, with a phase II clinical trial, whether a strategy including 2 NRTIs and raltegravir, as an alternative strategy to the classical triple therapy, shows an immunovirological response, at least, as good as the one obtained with the triple therapy. The hypothesis is that the low ART response observed in HIV-2 infection is due to a low virological strength of the ARTs used and that the combination of 2 NRTIs and raltegravir should show a therapeutic success of at least 50% at week 48.

Official Title
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ANRS 159 VIH-2 : Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients

Conditions
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HIV-2 Infection

Intervention / Treatment
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* Drug: emtricitabine / tenofovir disoproxil fumarate / raltegravir .


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥18 years HIV-2 mono infection, confirmed by ELISA and Western Blot test or Immunoblot, antiretroviral treatment-naive, whatever the duration and indication of prior treatments, indication to treatment, with at least one of the following criteria : type B or C events, CD4 lymphocytes count below 500/mm3 at screening-visit or CD4 lymphocytes count decrease of at least 50 cell/µL/year over the last 3 years with the last CD4 lymphocytes count within -/+ 10 % of the nadir, plasma HIV-2 RNA load over or equal to 100 copies/mL at screening-visit, Pneumocystis prophylaxis if CD4 lymphocytes count below 200/mm3, combined to a toxoplasmosis prophylaxis in case of a positive toxoplasmosis serology, French residency for at least one year, Written informed consent, signed by the participant and the investigator (at the latest on the screening-visit and prior any study related intervention) Affiliate or beneficiary of a social security system (State Medical Assistance is not a social security scheme). Exclusion Criteria: Absence of effective contraception method(women), Pregnancy, breastfeeding or wish for pregnancy during the trial, Curative treatment of a progressive opportunistic infection not compatible with those evaluated in the present study, Malignant or tumorous affection requiring chemotherapy or radiotherapy, Decompensated cirrhosis, Viral hepatitis C with a Metavir score over F2, Hemoglobinemia below 7g/dL, polynuclear neutrophils below 500/mm3, platelets below 50 000/mm3, creatinine clearance below 50 mL/mn, transaminase, alkaline phosphatase or bilirubin over 2.5N, Contraindication to one of the excipients of study treatments, Insuline-dependent diabetes mellitus not well controlled (with glycated haemoglobin (HbA1C) over 7%), Long-term corticosteroid treatment (more than 3 weeks of treatment), Judicial protection, legal guardianship, Participation in other therapeutic trial or comprising an exclusion period ongoing at the time of the screening-visit.

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: raltegravir / emtricitabine / tenofovir disoproxil fumarate<br> | Drug: emtricitabine / tenofovir disoproxil fumarate / raltegravir .<br>* emtricitabine : 200 mg/day and tenofovir disoproxil fumarate : 300 mg/day, included in one pill of Truvada® QD. raltegravir : 400 mg x 2/day, 400 mg in one pill of Isentress® BID.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Therapeutic Success | The participants will be considered in therapeutic success at Week 48 if they did not present any of the following events: Plasma HIV-2 RNA load over or equal to 100 copies/mL, starting from Week 24 and confirmed within the next 4 weeks, CD4 lymphocytes gain below 100/mm3 at Week 48 compared to the CD4 lymphocytes counts average between Week-4 and Week 0, Raltegravir permanent discontinuation, Death from any cause, New B or C events confirmed by an endpoint review committee | at Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Change in CD4 Lymphocytes Count at Week 12 |  | between Week 0 and Week 12 | 
| Number of Clinical and Biological Events |  | from Week 0 to Week 48 | 
| Median Change of CD4 Lymphocytes at Week 48 |  | between Week 0 and Week 48 | 
| Percentage of Patients With Plasma HIV-2 RNA < 40 Copies/mL |  | between Week 0 and Week 48 | 
| Number of Participants With Clinical Progression | Clinical progression is defined as the switch: from category A to B, C or death. from category B to C or death. | from Week 0 to Week 48 | 
| Minimal Observed Percentage of Participants With Moderate to Good Adherence Evaluated With ANRS Self-administered Questionnaire of Adherence |  | from Week 4 to Week 48 | 
| Number of Virological Failure Participants With Resistance Mutations | Virological failure is defined as plasma HIV-2 RNA load over or equal to 100 copies/mL after plasma HIV-2 RNA load below 100copies/mL, confirmed with a retest within the 4 following weeks. The number and type of mutations in the RT and integrase genes compared to week 0 is being reported. | from Week 0 to Week 48 | 
| Number of Participants With Treatment Switch or Discontinuation | Overall (regardless of the molecule) | from Week 0 to Week 48 | 
| Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 48 |  | at Week 48 | 
| Minimal Median of the Lower Dimension Out of the 4 Dimensions of the Quality of Life Questionnaire | The quality of life questionnaire is the Professional Quality of Life (PROQOL) questionnaire, including 4 dimensions: Physical health and symptoms, Relationship with others, Mental and cognitive functioning and Treatment impact For each scale, a score ranging from 0 (the worst answer) to 100 (the best answer) is calculated. | from Week 0 to Week 48 | 
| Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 24 |  | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-2